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KE Relationships

ID Upstream Event Downstream Event Creation Date Last Updated AOPs
1927 β-catenin activation Snail, Zeb, Twist activation May 29, 2019 May 29, 2019
    1924 Wnt ligand stimulation Frizzled activation May 29, 2019 May 29, 2019
      1145 Weakened, Colony Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
      • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
      • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
      • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
      • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
      • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
      • Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
      • Varroa mite infestation increases virus levels leading to colony loss/failure
      • Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure
      • Weather event contributes to colony loss/failure
      • Weather event contributes abnormal foraging leading to colony loss/failure
      • Nosema infection increases energetic demands leading to colony loss/failure
      • Nosema infection causes abnormal role change that leads to colony loss/failure
      • Queen egg-laying decrease leads to colony loss/failure
      2757 Weak, Procuticle protection Decrease, New cuticle secretion Aug 28, 2022 Aug 28, 2022
      • Knickkopf leading to mortality
      1639 Weak collagen matrix Notochord malformation Aug 3, 2017 Aug 3, 2017
      • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
      2693 Viable offspring, decreased Decrease, Population growth rate Jul 18, 2022 Jul 18, 2022
        3028 Vascular barrier disruption Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
        2084 cell injury Increase, Regenerative cell proliferation (urothelial cells) Apr 21, 2020 Apr 21, 2020
        • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
        699 Upregulated, Spindle assembly checkpoint protein Mad2-oocyte Increased, Chromosome misseggregation Nov 29, 2016 Dec 3, 2016
        • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
        1372 Up Regulation, Unsaturated fatty acid Perturbation of cholesterol Feb 15, 2017 Feb 15, 2017
        • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
        303 Up Regulation, TGFbeta1 expression Accumulation, Collagen Nov 29, 2016 Dec 3, 2016
          304 Up Regulation, TGFbeta1 expression Activation, Stellate cells Nov 29, 2016 Nov 29, 2016
            1371 Up Regulation, SREBF2 Up Regulation, Unsaturated fatty acid Feb 15, 2017 Feb 15, 2017
            • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
            493 Up Regulation, SCD-1 Increased, Triglyceride formation Nov 29, 2016 Dec 3, 2016
            • NR1I3 (CAR) suppression leading to hepatic steatosis
            • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
            1657 Up Regulation, SCD-1 Accumulation, Triglyceride Aug 31, 2017 Aug 31, 2017
            • AhR activation leading to hepatic steatosis
            507 Up Regulation, LDLR (low density lipoprotein receptor) Increased, LDL uptake Nov 29, 2016 Dec 3, 2016
            • AhR activation leading to hepatic steatosis
            492 Up Regulation, FAS Increased, De Novo FA synthesis Nov 29, 2016 Dec 3, 2016
            • NR1I3 (CAR) suppression leading to hepatic steatosis
            104 Up Regulation, CYP1B1 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Dec 3, 2016
              96 Up Regulation, CYP1A1 Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                2887 Up Regulation, CYP1A1 Increase, ROS Apr 13, 2023 Apr 13, 2023
                • AhR activation leading to liver fibrosis
                66 Up Regulation, CD36 Increase, FA Influx Nov 29, 2016 Mar 27, 2024
                • LXR activation leading to hepatic steatosis
                • Pregnane X Receptor (PXR) activation leads to liver steatosis
                501 Up Regulation, CD36 Increased, FA Influx Nov 29, 2016 Dec 3, 2016
                • AhR activation leading to hepatic steatosis
                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                • NR1I3 (CAR) suppression leading to hepatic steatosis
                2262 Up Regulation, CD36 Increased, Fatty acid uptake Jan 15, 2021 Jan 15, 2021
                  517 Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Increased, De Novo FA synthesis Nov 29, 2016 Dec 3, 2016
                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                  1161 Unknown, MIE Increased, Reactive oxygen species Nov 29, 2016 Dec 3, 2016
                  • unknown MIE leading to renal failure and mortality
                  2035 Unknown, MIE Unknown, Jan 26, 2020 Jan 26, 2020
                    2036 Unknown, MIE N/A, Unknown Jan 26, 2020 Jan 26, 2020
                      1732 Unfolded Protein Response General Apoptosis Apr 4, 2018 Apr 5, 2018
                      • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                      1866 Unfolded Protein Response Apoptosis Mar 6, 2019 Mar 6, 2019
                      • Inhibition of N-linked glycosylation leads to liver injury
                      2712 Unfolded Protein Response Increase, Cell death Jul 25, 2022 Jul 25, 2022
                        3041 Unfolded Protein Response Caspase activation Sep 14, 2023 Sep 14, 2023
                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                        1168 Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) Nov 29, 2016 Dec 3, 2016
                        • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                        1196 Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Imp Osteoporosis and vascular calcification, Bone deterioration Nov 29, 2016 Dec 3, 2016
                          2028 Inhibition, trypsin Increased monitor peptide Jan 8, 2020 Jan 8, 2020
                          • Trypsin inhibition leading to pancreatic acinar cell tumors
                          1281 TRPV1 activation, TRPV1 Opening of calcium channel, Calcium influx Nov 29, 2016 Nov 29, 2016
                            1271 TRPA1 activation, TRPA1 Receptor Opening of calcium channel, Calcium influx Nov 29, 2016 Nov 29, 2016
                            • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                            1284 TRPA1 activation, TRPA1 Receptor Non-neuronal production of IL-8/CXCL1, Epithelial irritation Nov 29, 2016 Dec 3, 2016
                              1576 TRPA1 activation, TRPA1 Receptor Generation of novel epitopes , Antigen presentation Jun 23, 2017 Jun 23, 2017
                                1275 Excitation, Trigeminal nerve excitation Cough, Dyspnea, Sneezing, Acute respiratory effect Nov 29, 2016 Dec 3, 2016
                                  1276 Excitation, Trigeminal nerve excitation Increased Airway Hyper-responsiveness,Cough, Dyspnea Nov 29, 2016 Dec 3, 2016
                                    1575 Excitation, Trigeminal nerve excitation SP (Substance P) release, Local increase of SP Jun 23, 2017 Jun 23, 2017
                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                    1578 Excitation, Trigeminal nerve excitation Increased CGRP Jun 23, 2017 Jun 23, 2017
                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                    1582 Excitation, Trigeminal nerve excitation Irritation induced sneezing Jun 23, 2017 Jun 23, 2017
                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                    1583 Excitation, Trigeminal nerve excitation Increased NKA Jun 23, 2017 Jun 23, 2017
                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                    1771 Increased Airway Hyper-responsiveness,Cough, Dyspnea Respiratory irritability Sep 24, 2018 Sep 24, 2018
                                      1456 Treat, carbamazepine Binding to VGSC Apr 14, 2017 Apr 14, 2017
                                      • Molecular events lead to epilepsy
                                      • presynaptic neuron 1 activation to epilepsy
                                      1589 Increased transcription of genes encoding acute phase proteins Systemic acute phase response Jun 29, 2017 Dec 19, 2023
                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                      2542 Torsades de Pointes Sudden cardiac death Dec 13, 2021 Dec 13, 2021
                                      • hERG channel blockade leading to sudden cardiac death
                                      2852 Torsades de Pointes Increased Mortality Jan 29, 2023 Jan 29, 2023
                                        2148 TLR4 activation Activation, JNK Jul 9, 2020 Jul 9, 2020
                                        • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                        2155 TLR4 activation Activation, TGF-beta pathway Jul 9, 2020 Jul 9, 2020
                                          2251 TLR4 activation AP-1 activation Dec 23, 2020 Dec 23, 2020
                                            2303 TLR Activation/Dysregulation Increased proinflammatory mediators Mar 29, 2021 Feb 7, 2023
                                            • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                            1763 Tissue resident cell activation Increased pro-inflammatory mediators Aug 2, 2018 Aug 2, 2018
                                            • Protein Alkylation leading to Liver Fibrosis
                                            • Increased DNA damage leading to increased risk of breast cancer
                                            • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                            2834 Tissue resident cell activation Increase, Pro-Inflammatory Mediators Jan 25, 2023 Feb 16, 2024
                                            • Deposition of Energy Leading to Learning and Memory Impairment
                                            444 T4 in neuronal tissue, Decreased BDNF, Reduced Nov 29, 2016 Apr 4, 2019
                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                            746 T4 in neuronal tissue, Decreased Hippocampal gene expression, Altered Nov 29, 2016 Aug 11, 2018
                                            • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            309 Thyroperoxidase, Inhibition TH synthesis, Decreased Nov 29, 2016 Nov 4, 2022
                                            • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                            • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                            • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                            • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                            • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                            • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                            • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                            366 Thyroperoxidase, Inhibition T4 in serum, Decreased Nov 29, 2016 Jul 8, 2022
                                            • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                            • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                            • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                            • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                            383 Thyroperoxidase, Inhibition Cognitive Function, Decreased Nov 29, 2016 Dec 3, 2016
                                              790 Thyroperoxidase, Inhibition Decrease, Incorporation of active iodide into iodotyrosines Nov 29, 2016 Dec 3, 2016
                                                1040 Thyroperoxidase, Inhibition Reduced, Anterior swim bladder inflation Nov 29, 2016 Feb 22, 2019
                                                  305 TH synthesis, Decreased T4 in serum, Decreased Nov 29, 2016 Oct 10, 2022
                                                  • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                  • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                  • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                  • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                  • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                  • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                  • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                  • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                  • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                  • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                  • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                  • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                  • Kidney dysfunction by decreased thyroid hormone
                                                  • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                  • Pendrin inhibition leading to altered amphibian metamorphosis
                                                  • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                  • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                  • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                  810 TH synthesis, Decreased Increased, Serum creatinine Nov 29, 2016 Dec 3, 2016
                                                  • Kidney dysfunction by decreased thyroid hormone
                                                  1504 TH synthesis, Decreased BDNF, Reduced May 10, 2017 Apr 4, 2019
                                                  • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                  1505 TH synthesis, Decreased GABAergic interneurons, Decreased May 10, 2017 May 29, 2018
                                                  • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                  1506 TH synthesis, Decreased Impairment, Learning and memory May 10, 2017 May 29, 2018
                                                  • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                  1768 TH synthesis, Decreased Reduction, Plasma 17beta-estradiol concentrations Sep 18, 2018 Sep 18, 2018
                                                  • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                  1636 Thiol protein adducts Inhibition of lysyl oxidase Aug 3, 2017 Aug 3, 2017
                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                  2019 Th17 cell migration and inflammation induction Skin disease Dec 27, 2019 Dec 27, 2019
                                                  • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                  2034 test Unknown, MIE Jan 26, 2020 Jan 26, 2020
                                                    2037 test N/A, Unknown Jan 26, 2020 Jan 26, 2020
                                                      541 inflammation Activation, AKT2 Nov 29, 2016 Dec 3, 2016
                                                      • AKT2 activation leading to hepatic steatosis
                                                      1590 Systemic acute phase response HDL-SAA formation Jun 29, 2017 Jun 29, 2017
                                                        2860 Systemic acute phase response Atherosclerosis Mar 28, 2023 Dec 18, 2023
                                                        • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                        110 Synthesis, De Novo Fatty Acid (FA) Accumulation, Triglyceride Nov 29, 2016 Mar 29, 2024
                                                        • LXR activation leading to hepatic steatosis
                                                        • Liver X Receptor (LXR) activation leads to liver steatosis
                                                        2504 Dysfunctional synapses Neuronal network function, Decreased Oct 26, 2021 Oct 26, 2021
                                                        • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                        • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                        2808 Dysfunctional synapses Impairment, Learning and memory Dec 11, 2022 Dec 11, 2022
                                                        • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                        3065 Dysfunctional synapses Impaired axonial transport Oct 17, 2023 Oct 17, 2023
                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                        3078 Dysfunctional synapses impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                        2362 Sustentacular cells, decrease olfacotry neurons, decrease Apr 26, 2021 Apr 26, 2021
                                                        • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                        2365 Sustentacular cells, decrease anosmia Apr 26, 2021 Apr 26, 2021
                                                        • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                        3216 Suppression, VLDL secretion Increased, Liver Steatosis May 9, 2024 May 9, 2024
                                                        • AhR activation leading to hepatic steatosis
                                                        1823 Suppression, Suppression of T-cell dependent antibody response (TDAR) Impairment of TDAR Dec 25, 2018 Dec 25, 2018
                                                          1259 Suppression, Suppression of T-cell dependent antibody production Impairment of TDAR Nov 29, 2016 Dec 3, 2016
                                                            1258 Suppression, Suppression of production of cytotoxic T-cells Impairment, T-cell dependent antibody response Nov 29, 2016 Dec 3, 2016
                                                              1260 Suppression, Suppression of production of cytotoxic T-cells Impairment of TDAR Nov 29, 2016 Dec 3, 2016
                                                                388 Suppression, Inflammatory cytokines Decreased, Lymphocytes Nov 29, 2016 Dec 3, 2016
                                                                • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                570 Suppression, Immune system Increased, Viral susceptibility Nov 29, 2016 Dec 3, 2016
                                                                • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                1255 Suppression, IL-2 and IL-4 production Interference, nuclear localization of NFAT Nov 29, 2016 Dec 3, 2016
                                                                  1510 Suppression, IL-2 and IL-4 production Impairment, T-cell dependent antibody response May 19, 2017 Jun 27, 2021
                                                                  • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                  1086 Suppression, Estrogen receptor (ER) activity Decrease, E2 blood concentrations at hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                  • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                  2580 Suppression, Estrogen receptor (ER) activity Increased, secretion of GnRH from hypothalamus Feb 26, 2022 Mar 1, 2022
                                                                  • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                  476 Suppression, Constitutive androstane receptor, NR1l3 Activation, LXR Nov 29, 2016 Dec 3, 2016
                                                                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                  477 Suppression, Constitutive androstane receptor, NR1l3 demethylation, PPARg promoter Nov 29, 2016 Dec 3, 2016
                                                                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                  2026 Suppression of STAT5 binding to cytokine gene promoters Suppression of IL-4 production Jan 5, 2020 Mar 30, 2021
                                                                  • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                  2027 Suppression of IL-4 production Impairment, TDAR Jan 5, 2020 Apr 4, 2021
                                                                  • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                  2001 Suppression of T cell activation Inhibition, Nuclear factor kappa B (NF-kB) Nov 17, 2019 Nov 17, 2019
                                                                    2004 Suppression of T cell activation Impairment of TDAR Nov 17, 2019 Mar 2, 2023
                                                                      2927 Suppression of T cell activation Impaired IL-1R1 signaling May 24, 2023 May 24, 2023
                                                                        2928 Suppression of T cell activation Impairment, T-cell dependent antibody response May 24, 2023 May 25, 2023
                                                                        • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                        1818 Suppressed NF-kB Suppressed DC activation Dec 25, 2018 Dec 25, 2018
                                                                          1826 Suppressed MyD88 Impairment of TDAR Jan 6, 2019 Jan 6, 2019
                                                                            1870 Suppressed MyD88 Inhibition, Nuclear factor kappa B (NF-kB) Mar 12, 2019 Mar 12, 2019
                                                                              1819 Suppressed DC activation Impaired antigen presentation Dec 25, 2018 Dec 25, 2018
                                                                                1817 Suppressed AP-1 Suppressed DC activation Dec 25, 2018 Dec 25, 2018
                                                                                  2896 Superoxide generation, increased Increase, Oxidative Stress Apr 24, 2023 Jun 1, 2023
                                                                                  • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                  2866 SDH, inhibited Superoxide generation, increased Apr 3, 2023 May 4, 2023
                                                                                  • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                  2895 SDH, inhibited Increase, Oxidative Stress Apr 24, 2023 Apr 24, 2023
                                                                                    1702 Interaction with the lung cell membrane Increased proinflammatory mediators Jan 5, 2018 Aug 29, 2023
                                                                                    • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                    • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                    • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                    2662 Interaction with the lung cell membrane Increased, Reactive oxygen species May 25, 2022 May 25, 2022
                                                                                    • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                    2663 Interaction with the lung cell membrane Increased, DNA damage and mutation May 25, 2022 May 25, 2022
                                                                                    • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                    2958 Interaction with the lung cell membrane Increased transcription of genes encoding acute phase proteins Jul 4, 2023 Dec 19, 2023
                                                                                    • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                    2959 Interaction with the lung cell membrane Systemic acute phase response Jul 4, 2023 Dec 19, 2023
                                                                                    • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                    2960 Interaction with the lung cell membrane Atherosclerosis Jul 4, 2023 Dec 18, 2023
                                                                                    • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                    1968 Substance - LS interaction Inhibition of LS function. Jul 3, 2019 Jul 3, 2019
                                                                                      3207 Binding PPAR isoforms Dysregulation of transcriptional expression within PPAR signaling network May 8, 2024 May 8, 2024
                                                                                        3208 Binding PPAR isoforms Decreased, Mitochondrial fatty acid beta-oxidation May 8, 2024 May 8, 2024
                                                                                          3220 Binding PPAR isoforms Disrupted PPAR isoform nuclear signaling May 14, 2024 May 23, 2024
                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                          2017 Stimulation of TLR7/8 Increase of IL-23 Dec 27, 2019 Dec 27, 2019
                                                                                          • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                          2141 Status epilepticus Overactivation, NMDARs May 21, 2020 May 21, 2020
                                                                                            2782 Status epilepticus Increased, glutamate Oct 12, 2022 Sep 3, 2023
                                                                                            • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                            2783 Status epilepticus Increased, Intracellular Calcium overload Oct 12, 2022 Jul 24, 2023
                                                                                            • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                            1024 stabilization, PPAR alpha co-repressor Decreased, PPARalpha transactivation of gene expression Nov 29, 2016 Jun 11, 2018
                                                                                            • Antagonist binding to PPARα leading to body-weight loss
                                                                                            1106 squamous metaplasia, aberrant basal cells Increased, Hyperplasia (glandular epithelial cells of endometrium) Nov 29, 2016 Dec 3, 2016
                                                                                            • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                            1734 Spermatocyte depletion Testicular atrophy May 22, 2018 Jul 28, 2021
                                                                                            • Histone deacetylase inhibition leading to testicular atrophy
                                                                                            1279 SP (Substance P) release, Local increase of SP Non-neuronal production of TNF, Epithelial irritation Nov 29, 2016 Nov 29, 2016
                                                                                              1574 SP (Substance P) release, Local increase of SP Increased Airway Hyper-responsiveness,Cough, Dyspnea Jun 23, 2017 Jun 23, 2017
                                                                                                1577 SP (Substance P) release, Local increase of SP Leukocyte infiltration Jun 23, 2017 Jun 23, 2017
                                                                                                  1772 SP (Substance P) release, Local increase of SP Respiratory irritability Sep 24, 2018 Sep 24, 2018
                                                                                                  • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                  2438 six1b expression, increased eya1 expression, inhibited Jul 14, 2021 Aug 13, 2021
                                                                                                  • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                  1499 Sexual behavior, decreased Decreased, Reproductive Success May 8, 2017 May 8, 2017
                                                                                                  • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                  1571 Serotonin 1A Receptor Agonism Release of G Proteins Jun 23, 2017 Jun 23, 2017
                                                                                                  • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                  • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                  2657 Sensory axonal peripheral neuropathy Increased Mortality May 16, 2022 May 16, 2022
                                                                                                  • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                  3066 Sensory axonal peripheral neuropathy Decreased, Neuronal network function in adult brain Oct 17, 2023 Oct 17, 2023
                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                  3067 Sensory axonal peripheral neuropathy Overactivation, NMDARs Oct 17, 2023 Oct 17, 2023
                                                                                                    1588 Sensing of the stressor Increased transcription of genes encoding acute phase proteins Jun 29, 2017 Jun 29, 2017
                                                                                                      2661 Secondary genotoxicity Increased, DNA damage and mutation May 25, 2022 May 25, 2022
                                                                                                      • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                      2052 SARS-CoV-2 cell entry Increased proinflammatory mediators Mar 1, 2020 Mar 1, 2020
                                                                                                        2302 SARS-CoV-2 cell entry TLR Activation/Dysregulation Mar 29, 2021 Mar 29, 2021
                                                                                                          2310 SARS-CoV-2 cell entry SARS-CoV-2 production Mar 30, 2021 Feb 7, 2023
                                                                                                          • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                          • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                          2314 SARS-CoV-2 cell entry Increased viral transcription and replication Apr 9, 2021 Apr 9, 2021
                                                                                                            2361 SARS-CoV-2 cell entry Sustentacular cells, decrease Apr 26, 2021 Apr 26, 2021
                                                                                                              2496 SARS-CoV-2 cell entry IFN-I response, antagonized Oct 24, 2021 Dec 12, 2023
                                                                                                              • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                              • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                              • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                              • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                              • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                              2510 SARS-CoV-2 cell entry Endothelial cell dysfunction Oct 28, 2021 Oct 28, 2021
                                                                                                                3036 Activation, RyR Increased, glutamate Sep 8, 2023 Sep 8, 2023
                                                                                                                • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                1845 ROS generation Oxidation of membrane lipids Feb 4, 2019 Jul 9, 2019
                                                                                                                • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                1846 ROS generation Oxidation/denatuation of membrane proteins Feb 4, 2019 Jul 9, 2019
                                                                                                                • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                1847 ROS generation Oxidation of DNA Feb 4, 2019 Feb 4, 2019
                                                                                                                  1361 ROS formation Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Feb 15, 2017 Feb 15, 2017
                                                                                                                  • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                  1915 Retinaldehyde dehydrogenase retinoic acid May 22, 2019 May 22, 2019
                                                                                                                  • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                  378 Response, Keratinocytes Activation, Dendritic Cells Nov 29, 2016 Nov 29, 2016
                                                                                                                    380 Response, Keratinocytes Activation/Proliferation, T-cells Nov 29, 2016 Dec 3, 2016
                                                                                                                      433 Respiratory distress/arrest Increased Mortality Nov 29, 2016 Dec 20, 2019
                                                                                                                      • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                      592 Respiratory distress/arrest N/A, hypoxia Nov 29, 2016 Dec 3, 2016
                                                                                                                      • Sodium channel inhibition leading to congenital malformations
                                                                                                                      2436 Repression of Gbx2 expression foxi1 expression, increased Jul 14, 2021 Aug 13, 2021
                                                                                                                      • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                      1648 Repressed expression of steroidogenic enzymes Reduction, Testosterone synthesis in Leydig cells Aug 11, 2017 Aug 11, 2017
                                                                                                                      • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                      108 Release, Cytokine Increase, Inflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                      • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                      925 Release, Cytokine Infiltration, Inflammatory cytokines Nov 29, 2016 Dec 3, 2016
                                                                                                                        994 Release, Cytokine Infiltration, Inflammatory cells Nov 29, 2016 Nov 29, 2016
                                                                                                                          1963 Release, Cytokine Recruitment of inflammatory cells Jul 3, 2019 Jul 3, 2019
                                                                                                                          • Frustrated phagocytosis-induced lung cancer
                                                                                                                          • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                          2454 Release, Cytokine Platelet activation, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                          • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                          2455 Release, Cytokine Neutrophil activation, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                          • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                          1564 Release of G Proteins Opening of GIRK channels Jun 8, 2017 Jun 8, 2017
                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                          1568 Release of G Proteins Inhibition of Ca Channels Jun 23, 2017 Jun 23, 2017
                                                                                                                          • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                          • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                          1081 relaxation, smooth muscle Proliferation/Clonal Expansion, smooth muscle Nov 29, 2016 Dec 3, 2016
                                                                                                                          • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                          315 Reduction, Vitellogenin synthesis in liver Reduction, Plasma vitellogenin concentrations Nov 29, 2016 Mar 20, 2017
                                                                                                                          • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                          • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                          • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                          • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                          • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                          • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                          337 Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Reduction, Cumulative fecundity and spawning Nov 29, 2016 Mar 20, 2017
                                                                                                                          • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                          • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                          • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                          • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                          • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                          • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                          • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                          2923 Reduction, the ratio of E2/11-KT in plasma Reduction, Plasma vitellogenin concentrations May 22, 2023 May 22, 2023
                                                                                                                          • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                          439 Reduction, Testosterone synthesis in Leydig cells Reduction of testosterone Nov 29, 2016 Dec 2, 2016
                                                                                                                            2125 Reduction, Testosterone synthesis in Leydig cells Decrease, testosterone levels May 11, 2020 May 1, 2024
                                                                                                                            • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                            • PPARα activation in utero leading to impaired fertility in males
                                                                                                                            • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                            • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                            302 Reduction, Testosterone synthesis by ovarian theca cells Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Mar 20, 2017
                                                                                                                            • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                            268 Reduction, Prostaglandin E2 concentration N/A, Gap Nov 29, 2016 Dec 3, 2016
                                                                                                                            • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                            1989 Reduction, progesterone uptake, decresed maturation Impaired ovulation Oct 3, 2019 Oct 3, 2019
                                                                                                                            • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                            1987 Reduction, Progesterone synthesis Reduction, Plasma progesterone concentration Oct 3, 2019 Oct 3, 2019
                                                                                                                            • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                            255 Reduction, Plasma vitellogenin concentrations Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Nov 29, 2016 Mar 20, 2017
                                                                                                                            • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                            • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                            • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                            • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                            • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                            • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                            • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                            1769 Reduction, Plasma vitellogenin concentrations Reduction, Cumulative fecundity and spawning Sep 18, 2018 Sep 18, 2018
                                                                                                                            • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                            • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                            1882 Reduction, Plasma vitellogenin concentrations Reduction, egg production and spawning Apr 18, 2019 Apr 18, 2019
                                                                                                                              1988 Reduction, Plasma progesterone concentration Reduction, progesterone uptake, decresed maturation Oct 3, 2019 Oct 3, 2019
                                                                                                                              • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                              252 Reduction, Plasma 17beta-estradiol concentrations Reduction, Vitellogenin synthesis in liver Nov 29, 2016 Mar 20, 2017
                                                                                                                              • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                              • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                              • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                              • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                              • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                              253 Reduction, Plasma 17beta-estradiol concentrations Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Nov 29, 2016 Nov 29, 2016
                                                                                                                                392 Reduction, Plasma 17beta-estradiol concentrations irregularities, ovarian cycle Nov 29, 2016 Dec 3, 2016
                                                                                                                                • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                1386 Reduction, Plasma 17beta-estradiol concentrations Reduction, Plasma vitellogenin concentrations Mar 17, 2017 Oct 18, 2018
                                                                                                                                • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                2922 Reduction, Plasma 17beta-estradiol concentrations Reduction, the ratio of E2/11-KT in plasma May 22, 2023 May 22, 2023
                                                                                                                                • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                1018 Reduction, NFAT/AP-1 complex formation Suppression, Suppression in mixed lymphocyte reaction (MLR) Nov 29, 2016 Dec 3, 2016
                                                                                                                                  1019 Reduction, NFAT/AP-1 complex formation Suppression, Suppression of T-cell dependent antibody response (TDAR) Nov 29, 2016 Dec 3, 2016
                                                                                                                                    1020 Reduction, NFAT/AP-1 complex formation Impairment, T-cell dependent antibody response Nov 29, 2016 Dec 3, 2016
                                                                                                                                      1021 Reduction, NFAT/AP-1 complex formation Relief, Relief of atopic dermatitis Nov 29, 2016 Dec 3, 2016
                                                                                                                                        1022 Reduction, NFAT/AP-1 complex formation Impairment of TDAR Nov 29, 2016 Dec 3, 2016
                                                                                                                                          1256 Reduction, NFAT/AP-1 complex formation Suppression, Suppression of production of cytotoxic T-cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                            1257 Reduction, NFAT/AP-1 complex formation Suppression, Suppression of T-cell dependent antibody production Nov 29, 2016 Dec 3, 2016
                                                                                                                                              1509 Reduction, NFAT/AP-1 complex formation Suppression, IL-2 and IL-4 production May 19, 2017 Jun 27, 2021
                                                                                                                                              • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                              683 Reduction, Neuronal synaptic inhibition Generation, Amplified excitatory postsynaptic potential (EPSP) Nov 29, 2016 May 15, 2018
                                                                                                                                              • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                              667 Reduction, Ionotropic GABA receptor chloride channel conductance Reduction, Neuronal synaptic inhibition Nov 29, 2016 Apr 29, 2019
                                                                                                                                              • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                              143 Reduction, Gonadotropins, circulating concentrations Reduction, Testosterone synthesis by ovarian theca cells Nov 29, 2016 Mar 20, 2017
                                                                                                                                              • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                              460 Reduction of testosterone Increase, Luteinizing hormone (LH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                608 Reduction of testosterone Malformation, Male reproductive tract Nov 29, 2016 Dec 2, 2016
                                                                                                                                                  1649 Reduction of testosterone Decreased sperm quantity or quality in the adult, Decreased fertility Aug 11, 2017 Aug 11, 2017
                                                                                                                                                    123 Reduction, Eggshell thickness N/A, Reproductive failure Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                    94 Reduction, Cumulative fecundity and spawning Decrease, Population growth rate Nov 29, 2016 Mar 20, 2017
                                                                                                                                                    • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                    • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                    • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                                                    • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                    • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                    • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                    • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                    • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                    • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                    • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                    • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                    2142 Reduction, Cumulative fecundity and spawning Decline, Population May 25, 2020 May 25, 2020
                                                                                                                                                      2924 Reduction, Cumulative fecundity and spawning Decreased, Population trajectory May 22, 2023 May 22, 2023
                                                                                                                                                      • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                      438 Reduction, Cholesterol transport in mitochondria Reduction, Testosterone synthesis in Leydig cells Nov 29, 2016 Dec 2, 2016
                                                                                                                                                      • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                      59 Reduction, Ca and HCO3 transport to shell gland Reduction, Eggshell thickness Nov 29, 2016 Dec 3, 2016
                                                                                                                                                      • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                      36 Reduction, Angiogenesis Impairment, Endothelial network Nov 29, 2016 Jan 18, 2022
                                                                                                                                                      • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                      2145 Reduction, E2 Synthesis by the undifferentiated gonad Increased, Differentiation to Testis Jun 15, 2020 Jul 11, 2022
                                                                                                                                                      • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                      5 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Reduction, Plasma 17beta-estradiol concentrations Nov 29, 2016 Mar 20, 2017
                                                                                                                                                      • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                      • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                      • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                      • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                      • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                      • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                      1933 Reduction, androstenedione Decrease, testosterone level Jun 3, 2019 Jun 3, 2019
                                                                                                                                                        3229 Reduction, androstenedione Decrease, testosterone levels May 24, 2024 May 24, 2024
                                                                                                                                                        • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                        1932 Reduction, DHEA Decrease, testosterone level Jun 3, 2019 Jun 3, 2019
                                                                                                                                                          3228 Reduction, DHEA Decrease, testosterone levels May 24, 2024 May 24, 2024
                                                                                                                                                          • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                          1894 Reduction of melanosome level Reduction fo Pigmentation pattern May 3, 2019 May 3, 2019
                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                          1892 Reduction of L-Dopaquinone Reduction in melanin level May 3, 2019 May 3, 2019
                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                          1638 Reduction of collagen crosslinking Weak collagen matrix Aug 3, 2017 Aug 3, 2017
                                                                                                                                                          • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                          396 reduction in ovarian granulosa cells, Aromatase (Cyp19a1) Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                          • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                          1893 Reduction in melanin level Reduction of melanosome level May 3, 2019 May 3, 2019
                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                          1895 Reduction fo Pigmentation pattern Decrease, Population growth rate May 3, 2019 May 3, 2019
                                                                                                                                                          • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                          587 Reduced, swimming speed Reduced, feeding 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Sodium channel inhibition leading to reduced survival
                                                                                                                                                          • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                          588 Reduced, swimming speed Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Sodium channel inhibition leading to reduced survival
                                                                                                                                                          • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                          • sodium channel inhibition leading to increased predation
                                                                                                                                                          1641 Reduced, Swimming performance Growth, reduction Aug 3, 2017 Aug 3, 2017
                                                                                                                                                          • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                          1642 Reduced, Swimming performance Decreased, survival Aug 3, 2017 Aug 3, 2017
                                                                                                                                                          • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                          2081 Reduced, Swimming performance Decrease, Population growth rate Apr 21, 2020 Jun 4, 2020
                                                                                                                                                          • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                          2212 Reduced, Swimming performance Increased Mortality Nov 30, 2020 Sep 8, 2021
                                                                                                                                                          • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                          • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                          • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                          • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                          • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                          673 Reduced, Spawning behavior Reduced, Ability to attract spawning mates Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                          1558 Reduced, SHP activity Activated, LXR Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                          675 Reduced, Reproductive Success Decrease, Population growth rate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                          1541 Reduced, PTGS2 function Decreased, angiogenesis Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                          1543 Reduced, PTGS2 function Increased, leukocyte adherence Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                          1532 Reduced, PTGS1 function Reduced, platelet aggregation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                          1534 Reduced, PTGS1 function Decreased, mucosal blood flow Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                          1537 Reduced, PTGS1 function Decreased, mucous Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                          1539 Reduced, PTGS1 function Decreased, bicarbonate Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                          685 Reduced, Prostaglandins, ovary Decrease, Ovulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                          671 Reduced, Prostaglandin F2alpha synthesis, ovary Reduced, Prostaglandin F2alpha concentration, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                          672 Reduced, Prostaglandin F2alpha concentration, plasma Reduced, Spawning behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                          678 Reduced, Prostaglandin F2alpha concentration, plasma Reduced, Pheromone release Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                          690 Reduced, Prostaglandin E2 concentration, hypothalamus Reduced, Gonadotropin releasing hormone, hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                          357 Reduced, Presynaptic release of glutamate Synaptogenesis, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                          1551 Reduced, presynaptic neuron 2 activity Decreased, GABA Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                          1560 Reduced, PPARalpha Reduced, HSD17B4 activity Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NFE2/Nrf2 repression to steatosis
                                                                                                                                                          1028 Reduced, Posterior swim bladder inflation Reduced, Swimming performance Nov 29, 2016 Sep 3, 2021
                                                                                                                                                          • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                          • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                          1031 Reduced, Posterior swim bladder inflation Reduced, Anterior swim bladder inflation Nov 29, 2016 Nov 20, 2020
                                                                                                                                                            2213 Reduced, Posterior swim bladder inflation Increased Mortality Nov 30, 2020 Sep 8, 2021
                                                                                                                                                            • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                            • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                            1533 Reduced, platelet aggregation Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                            • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                            679 Reduced, Pheromone release Reduced, Ability to attract spawning mates Nov 29, 2016 Dec 3, 2016
                                                                                                                                                            • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                            1536 Reduced, mucosal defense Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                            • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                            • Helicobacter pylori to gastric ulcer
                                                                                                                                                            1548 Reduced, mucosal defense Helicobacter pylori infection Jun 2, 2017 Jun 2, 2017
                                                                                                                                                              697 Reduced, Meiotic prophase I/metaphase I transition, oocyte Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                              693 Reduced, Maturation inducing steroid, plasma Reduced, Maturation inducing steroid receptor signalling, oocyte Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                              694 Reduced, Maturation inducing steroid receptor signalling, oocyte Increased, cyclic adenosine monophosphate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                              698 Reduced, Maturation inducing steroid receptor signalling, oocyte Upregulated, Spindle assembly checkpoint protein Mad2-oocyte Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                              692 Reduced, Luteinizing hormone (LH), plasma Reduced, Maturation inducing steroid, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                              1561 Reduced, HSD17B4 activity Reduced, fatty acid beta oxidation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                              • NFE2/Nrf2 repression to steatosis
                                                                                                                                                              2231 Reduced, Hearing Increased Mortality Dec 8, 2020 Dec 8, 2020
                                                                                                                                                              • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                              691 Reduced, Gonadotropin releasing hormone, hypothalamus Reduced, Luteinizing hormone (LH), plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                              1553 Reduced, GABA-A receptor activation Decreased, intracellular chloride Jun 2, 2017 Jun 2, 2017
                                                                                                                                                              • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                              1557 Reduced, FXR activity Reduced, SHP activity Jun 2, 2017 Jun 2, 2017
                                                                                                                                                              • NFE2/Nrf2 repression to steatosis
                                                                                                                                                              558 Reduced, Food storage Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                562 Reduced, Food storage impaired, Larval development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                589 Reduced, feeding 1 Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                596 Reduced, feeding 1 Reduced, survival Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                3215 Reduced, fatty acid beta oxidation Increased, Liver Steatosis May 9, 2024 May 9, 2024
                                                                                                                                                                • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                566 Reduced, Brood care impaired, Larval development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure
                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                1523 Reduced, BDNF Decreased, neuroplasticity May 31, 2017 May 31, 2017
                                                                                                                                                                • Mental stress to depression
                                                                                                                                                                578 Reduced, Antiseptic incorporated in food Abnormal, Roll change within caste Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                1032 Reduced, Anterior swim bladder inflation Reduced, Hearing Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                  1034 Reduced, Anterior swim bladder inflation Reduced, Swimming performance Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                  • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                  • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                  • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                  674 Reduced, Ability to attract spawning mates Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                  • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                  • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                  1975 Reduced tidal volume Impaired oxygenation of the blood Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                    2257 Reduced tidal volume Impaired lung function Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                      2367 Reduced tidal volume Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                      • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                      2480 Ovarian follicle pool, reduced Decreased fertility, Reduced number of oocytes ovulated Sep 12, 2021 Sep 12, 2021
                                                                                                                                                                        2487 Ovarian follicle pool, reduced impaired, Fertility Oct 10, 2021 Oct 10, 2021
                                                                                                                                                                          2525 Ovarian follicle pool, reduced irregularities, ovarian cycle Oct 29, 2021 Nov 12, 2021
                                                                                                                                                                          • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                          975 reduced production, VEGF Impairment, Endothelial network Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                          • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                          2407 reduced production, VEGF abnormal, placental labyrinth vasculature morphology May 31, 2021 May 31, 2021
                                                                                                                                                                          • AhR activation leading to preeclampsia
                                                                                                                                                                          3190 Reduced number of oligodendrocytes Hypomyelination Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                          348 BDNF, Reduced Aberrant, Dendritic morphology Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                          353 BDNF, Reduced Cell injury/death Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                          354 BDNF, Reduced Reduced, Presynaptic release of glutamate Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                          445 BDNF, Reduced Down Regulation, K-Cl co-transporter 2 (KCC2) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                            448 BDNF, Reduced Synaptogenesis, Decreased Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                            870 BDNF, Reduced GABAergic interneurons, Decreased Nov 29, 2016 Jan 19, 2018
                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                            1507 BDNF, Reduced Impairment, Learning and memory May 10, 2017 May 29, 2018
                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                            1171 Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction Impaired recruitment , Population trajectory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                            • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                            974 reduced dimerization, ARNT/HIF1-alpha reduced production, VEGF Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                            • AhR activation leading to preeclampsia
                                                                                                                                                                            3127 Reduced cortical thickness Microcephalus Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                              3143 Reduced cortical thickness Microcephaly Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                              2695 Reduced complex sphingolipids Affected folate transporter Jul 19, 2022 Jul 20, 2022
                                                                                                                                                                              • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                              1447 Reduce expression, BDNF Decreased, neuroplasticity Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                              • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                              • Mental stress to agitation
                                                                                                                                                                              • Serotonin transporter activation to agitation
                                                                                                                                                                              • Serotonin transporter activation to depression
                                                                                                                                                                              1848 Radical generation DNA photo-adducts Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                1849 Radical generation Protein photo-adducts Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                  2679 Pulmonary inflammation Chronic obstructive pulmonary disease Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                  • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                  1729 Protein Adduct Formation Unfolded Protein Response Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                  • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                  1837 Proteasomal dysfunction Airway epithelial injury Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                  • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                  3044 Proteasomal dysfunction Accumulation, misfolded proteins Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                  • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                  2912 prostatic intraepithelial neoplasia Prostate cancer May 11, 2023 May 11, 2023
                                                                                                                                                                                  • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                  240 Propagation, Oxidative stress Down Regulation, Gulcose-6-phosphate dehydrogenase Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                  241 Propagation, Oxidative stress Damaging, Red blood cells; hemolysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                  1104 Promotion, SIX-1 postive basal-type progenitor cells Proliferation/Clonal Expansion, aberrant basal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                  2830 Promotion, ovarian granular cell tumors Promotion, Ovarian Cancer Jan 13, 2023 Jan 13, 2023
                                                                                                                                                                                    2829 Promotion, ovarian adenomas Promotion, Ovarian Cancer Jan 13, 2023 Mar 11, 2023
                                                                                                                                                                                    • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                    1111 prolonged, estrus Increased, circulating estrogen levels Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                    • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                    1112 prolonged, estrus Increased, prolactin exposure Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                    1098 prolonged, elevation of serun CCK Increased, Cellular proliferation / hyperplasia of acinar cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                    604 prolonged, Depolarization of neuronal membrane Overactivation, Neuronotransmitter release Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                    • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                    2429 TLR9 activation MyD88 activation Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                    • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                    2433 TLR9 activation inflammasome activity, increased Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                    • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                    2541 Prolongation of QT interval Torsades de Pointes Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                    • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                    2853 Prolongation of QT interval Occurrence, cardiac arrhythmia Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                      2540 Prolongation of Action Potential Prolongation of QT interval Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                      • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                      1082 Proliferation/Clonal Expansion, smooth muscle Hypertrophy/hyperplasia, smooth muscle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                      • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                      1105 Proliferation/Clonal Expansion, aberrant basal cells squamous metaplasia, aberrant basal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                      • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                      69 Proliferation, Cell proliferation in the absence of cytotoxicity Hyperplasia, Hyperplasia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                      • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                      332 Production, VEGF-A Binding, VEGF-A Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                        333 Production, VEGF-A Decreased, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                          276 Production, Reactive oxygen species Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                          • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                          931 Production, Reactive oxygen species Cholestasis, Pathology Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                            93 Production, Critical Metabolites (CGA 330050 and CGA 265307) Induction, Liver “Dysfunctional” Changes by CGA 330050 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                            • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                            1358 Production of α-smooth muscle actin Lung fibrosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                              1283 Production of nerve growth factor , Epithelial irritation SP (Substance P) release, Local increase of SP Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                1102 prepubertal increase, Estrogen receptor (ER) activity Activation, estrogen receptor alpha Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                1179 premature, spawning 1 Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                  1211 premature, Spawning Increased, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                    1222 premature, Spawning Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                      2607 Premature differentiation Microcephaly Mar 21, 2022 Mar 21, 2022
                                                                                                                                                                                                        3107 Premature differentiation decline, neural progenitor cells Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                        2070 Porcupine-induced Wnt secretion and Wnt signaling activation beta-catenin activation Mar 23, 2020 Nov 9, 2021
                                                                                                                                                                                                        • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                        2458 Platelet-neutrophil interactions, Increased Thromboinflammation, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                        • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                        2456 Platelet activation, Increased Platelet-neutrophil interactions, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                        • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                        2151 Pin-1 activation TGFbeta expression Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                        • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                        1377 Perturbation of cholesterol Hepatotoxicity Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                        • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                        1125 persistent, cytotoxicity (pleura or peritoneum) Increased, inflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                        • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                        1126 persistent, cytotoxicity (pleura or peritoneum) Increased, Oxidative Stress Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                        • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                        256 demethylation, PPARg promoter Decrease, Aromatase (Cyp19a1) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                          395 demethylation, PPARg promoter reduction in ovarian granulosa cells, Aromatase (Cyp19a1) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                            411 demethylation, PPARg promoter Up Regulation, CD36 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                            • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                            487 demethylation, PPARg promoter Activation, SREBF1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                            • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                            1402 demethylation, PPARg promoter Activation, SREBP-1 Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                              1424 demethylation, PPARg promoter Activation, FAS Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                1608 demethylation, PPARg promoter Activation of specific nuclear receptors, PPAR-gamma activation Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                1659 demethylation, PPARg promoter Increased, FA Influx Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                2988 demethylation, PPARg promoter Activation of PPAR Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                2516 Pericyte dysfunction Endothelial cell dysfunction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                  236 Peptide Oxidation Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                    764 Peptide Oxidation Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                      765 Peptide Oxidation Increase, Cytotoxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                      • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                      922 Peptide Oxidation Mitochondrial dysfunction Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                        923 Peptide Oxidation Release, Cytokine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                          932 Peptide Oxidation Cholestasis, Pathology Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                          • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                          948 Peptide Oxidation Oxidation, Glutathione Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                            980 Peptide Oxidation Decrease, GTPCH-1 Nov 29, 2016 Sep 28, 2017
                                                                                                                                                                                                                            • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                            992 Peptide Oxidation Decrease, AKT/eNOS activity Nov 29, 2016 Oct 16, 2017
                                                                                                                                                                                                                            • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                            1237 Peptide Oxidation Increased activation, Nuclear factor kappa B (NF-kB) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                              1379 Peptide Oxidation Activation, JNK Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                              • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                              1467 Peptide Oxidation Increase, DNA Damage Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                1698 Peptide Oxidation S-Glutathionylation, eNOS Nov 16, 2017 Nov 20, 2017
                                                                                                                                                                                                                                • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                3083 Parkinsonian motor deficits Increase, Mortality Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                1711 p21 (CDKN1A) expression, increase Cell cycle, disrupted Jan 21, 2018 Jul 25, 2018
                                                                                                                                                                                                                                  1282 Oxidization of biomolecules, Lipid bilayer and cellular proteins TRPA1 activation, TRPA1 Receptor Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                    1285 Oxidization of biomolecules, Lipid bilayer and cellular proteins Generation of novel epitopes , Antigen presentation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                      1286 Oxidization of biomolecules, Lipid bilayer and cellular proteins Production of nerve growth factor , Epithelial irritation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                        1727 Oxidative Stress in Brain Lipid Peroxidation Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                        • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                        1730 Oxidative Stress in Brain Unfolded Protein Response Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                        • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                        2655 Oxidative Stress in Brain N/A, Neurodegeneration May 16, 2022 May 16, 2022
                                                                                                                                                                                                                                        • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                        2952 Oxidative Stress in Brain Neuronal network function, Decreased Jun 21, 2023 Jun 21, 2023
                                                                                                                                                                                                                                        • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                        3062 Oxidative Stress in Brain Decreased, Neuronal network function in adult brain Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                        1513 Oxidative Stress Hepatocytotoxicity May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                        1516 Oxidative Stress Liver Cancer May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                        1685 Oxidative Stress Glutamate dyshomeostasis Nov 9, 2017 Feb 6, 2020
                                                                                                                                                                                                                                        • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                        1690 Oxidative Stress Cell injury/death Nov 9, 2017 Feb 7, 2020
                                                                                                                                                                                                                                        • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                        2008 Oxidative Stress Wnt ligand stimulation Dec 3, 2019 Dec 3, 2019
                                                                                                                                                                                                                                          2289 Oxidative Stress Coagulation Mar 25, 2021 Mar 25, 2021
                                                                                                                                                                                                                                            2449 Oxidative Stress CFTR Function, Decreased Jul 30, 2021 Sep 28, 2021
                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                            2450 Oxidative Stress FOXJ1 Protein, Decreased Aug 2, 2021 Sep 28, 2021
                                                                                                                                                                                                                                            • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                            2451 Oxidative Stress CBF, Decreased Aug 2, 2021 Mar 24, 2023
                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                                                                                                                            2505 Oxidative Stress p-Tau Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                            • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                            2674 Oxidative Stress Pulmonary inflammation Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                            • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                            2714 Oxidative Stress Mitochondrial Injury Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                            2716 Oxidative Stress Increase, Cell death Jul 25, 2022 Mar 22, 2023
                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                            2771 Oxidative Stress Altered Signaling Sep 28, 2022 Feb 13, 2024
                                                                                                                                                                                                                                            • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                            • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                            2772 Oxidative Stress Increased pro-inflammatory mediators Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                            • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                            2774 Oxidative Stress Altered, Nitric Oxide Levels Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                            • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                            2776 Oxidative Stress Increase, Endothelial Dysfunction Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                            • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                            2810 Oxidative Stress Increase, Oxidative DNA damage Dec 16, 2022 Mar 8, 2024
                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                            2811 Oxidative Stress Increase, DNA strand breaks Dec 16, 2022 Mar 8, 2024
                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                            • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                            • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                            2812 Oxidative Stress Modified Proteins Dec 16, 2022 Mar 30, 2023
                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                            2818 Oxidative Stress Cataracts Dec 18, 2022 Mar 11, 2024
                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                            2827 Oxidative Stress Mitochondrial dysfunction EMPTY Jan 9, 2023 Jan 9, 2023
                                                                                                                                                                                                                                              2833 Oxidative Stress Tissue resident cell activation Jan 25, 2023 Feb 13, 2024
                                                                                                                                                                                                                                              • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                              2846 Oxidative Stress Altered Bone Cell Homeostasis Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                              • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                              2975 Oxidative Stress Increase, Inflammation Jul 31, 2023 Oct 19, 2023
                                                                                                                                                                                                                                              • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                              3047 Oxidative Stress Accumulation, misfolded proteins Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                              3048 Oxidative Stress Proteasomal dysfunction Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                              3116 Oxidative Stress Increased, LPO Jan 24, 2024 Jun 18, 2024
                                                                                                                                                                                                                                              • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                              • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                                                                                                                                              3129 Oxidative Stress Mitochondrial dysfunction Feb 17, 2024 Feb 17, 2024
                                                                                                                                                                                                                                              • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                              3233 Oxidative Stress Chronic kidney disease Jun 4, 2024 Jun 4, 2024
                                                                                                                                                                                                                                              • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                                                                                                                                              1851 Oxidation/denatuation of membrane proteins Inflammatory events Feb 4, 2019 Jul 9, 2019
                                                                                                                                                                                                                                              • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                              864 Oxidation, Uroporphyrinogen Accumulation, Highly carboxylated porphyrins Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                865 Oxidation, Uroporphyrinogen Inhibition, UROD Nov 29, 2016 May 30, 2018
                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                954 Oxidation, Glutathione S-Glutathionylation, eNOS Nov 29, 2016 Sep 28, 2017
                                                                                                                                                                                                                                                  2459 Oxidation, Glutathione Increased, Reactive oxygen species Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                  • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                  1850 Oxidation of membrane lipids Inflammatory events Feb 4, 2019 Jul 9, 2019
                                                                                                                                                                                                                                                  • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                  1852 Oxidation of DNA Inflammatory events Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                    661 Overwhelmed, Mitochondrial DNA repair mechanisms Accumulation, Damaged mitochondrial DNA Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                    • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                    2404 Overexpression of rasl11b Decrease, Cell proliferation May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                    • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                    361 Overactivation, NMDARs Increased, Intracellular Calcium overload Nov 29, 2016 Sep 10, 2023
                                                                                                                                                                                                                                                    • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                    • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                    • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                    2781 Overactivation, NMDARs Status epilepticus Oct 12, 2022 Sep 3, 2023
                                                                                                                                                                                                                                                    • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                    2806 Overactivation, NMDARs Loss of drebrin Dec 11, 2022 Dec 11, 2022
                                                                                                                                                                                                                                                    • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                    3038 Overactivation, NMDARs Increase, Cell membrane depolarization Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                    3068 Overactivation, NMDARs AchE Inhibition Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                    3069 Overactivation, NMDARs Decreased, Neuronal network function in adult brain Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                    3071 Overactivation, NMDARs Neuroinflammation Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                    605 Overactivation, Neuronotransmitter release Overactivation, muscle contraction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                    • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                    606 Overactivation, muscle contraction Increased, Ataxia, paralysis, or hyperactivity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                    • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                    3040 Opening VGCCs Increased, Intracellular Calcium overload Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                    1565 Opening of GIRK channels hyperpolarisation, neuron Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                    • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                    • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                    1272 Opening of calcium channel, Calcium influx Sensory Airway Irritation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                      1274 Opening of calcium channel, Calcium influx Excitation, Trigeminal nerve excitation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                      • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                      1280 Opening of calcium channel, Calcium influx SP (Substance P) release, Local increase of SP Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                        2363 olfacotry neurons, decrease Olfactory epithelium degeneration Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                        • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                        2366 olfacotry neurons, decrease anosmia Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                        • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                        2364 Olfactory epithelium degeneration anosmia Apr 26, 2021 Apr 26, 2021
                                                                                                                                                                                                                                                        • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                        943 Occurrence, Transdifferentiation of ciliated epithelial cells Goblet cell metaplasia Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                          1133 Occurrence, tophi (urate) deposition Occurrence, renal proximal tubular necrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                          • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                          • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                          1134 Occurrence, renal proximal tubular necrosis Increased, blood potassium concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                          • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                          • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                          • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                          1156 Occurrence, renal proximal tubular necrosis Increased, blood uric acid concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                          • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                          • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                          2647 Occurrence, renal proximal tubular necrosis Occurrence, Kidney toxicity Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                          • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                          1139 Occurrence, renal ischemia Occurrence, renal proximal tubular necrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                            1159 Occurrence, renal ischemia Increased, Oxidative Stress Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                            • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                            990 Goblet cell metaplasia Hypersecretion, Mucus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                              1313 Goblet cell metaplasia Increase, Mucin production Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                2471 Goblet cell metaplasia Chronic, Mucus hypersecretion Aug 26, 2021 Aug 27, 2021
                                                                                                                                                                                                                                                                  2648 Occurrence, Kidney toxicity Increased, Kidney Failure Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                  • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                  989 Goblet cell hyperplasia Hypersecretion, Mucus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                    1312 Goblet cell hyperplasia Increase, Mucin production Nov 29, 2016 Aug 11, 2021
                                                                                                                                                                                                                                                                      2472 Goblet cell hyperplasia Chronic, Mucus hypersecretion Aug 26, 2021 Aug 30, 2021
                                                                                                                                                                                                                                                                        1890 Occurrence, Focal Seizure Increased, glutamate Apr 22, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                        1998 Occurrence, Focal Seizure Overactivation, NMDARs Nov 13, 2019 Nov 13, 2019
                                                                                                                                                                                                                                                                          1861 Occurrence, Epileptic seizure Increased, glutamate Feb 13, 2019 Feb 13, 2019
                                                                                                                                                                                                                                                                            1999 Occurrence, Epileptic seizure Overactivation, NMDARs Nov 13, 2019 Nov 13, 2019
                                                                                                                                                                                                                                                                              817 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Glomerular filtration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              818 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Renal plasma flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              819 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Sodium reabsorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              820 Occurrence, Cytoplasmic vacuolization (Renal tubule) Decreased, Renal ability to dilute urine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              825 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Glomerular filtration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              826 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Renal plasma flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              827 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Sodium reabsorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              828 Occurrence, Cytoplasmic vacuolization (podocyte) Decreased, Renal ability to dilute urine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              857 Occurrence, Cytoplasmic vacuolization (kupffer cell) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                              858 Occurrence, Cytoplasmic vacuolization (kupffer cell) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                              851 Occurrence, Cytoplasmic vacuolization (hepatocyte) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                              852 Occurrence, Cytoplasmic vacuolization (hepatocyte) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                              855 Occurrence, Cytoplasmic vacuolization (Bile duct cell) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                              856 Occurrence, Cytoplasmic vacuolization (Bile duct cell) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                              821 Occurrence, Cystic dilatation (renal tubule) Decreased, Glomerular filtration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              822 Occurrence, Cystic dilatation (renal tubule) Decreased, Renal plasma flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              823 Occurrence, Cystic dilatation (renal tubule) Decreased, Sodium reabsorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              824 Occurrence, Cystic dilatation (renal tubule) Decreased, Renal ability to dilute urine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                              1136 Occurrence, cardiac arrthymia Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                1141 Occurrence, cardiac arrhythmia Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                2854 Occurrence, cardiac arrhythmia Increased,Cardiac dysfunction Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                  853 Occurrence, Ballooning degeneration (hepatocyte) Induction, Microvesicular fat Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                  • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                  854 Occurrence, Ballooning degeneration (hepatocyte) Formation, Mallory body Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                  • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                  630 Occurrence, A paroxysmal depolarizing shift Occurrence, Epileptic seizure Nov 29, 2016 May 22, 2018
                                                                                                                                                                                                                                                                                  • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                  1640 Notochord malformation Reduced, Swimming performance Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                  • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                  884 Not Increased, Circulating Ketone Bodies Increased, Catabolism of Muscle Protein Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                  • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                  1277 Non-neuronal production of TNF, Epithelial irritation Leukocyte infiltration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                    1288 Non-neuronal production of TNF, Epithelial irritation Opening of calcium channel, Calcium influx Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                      1287 Non-neuronal production of IL-8/CXCL1, Epithelial irritation Opening of calcium channel, Calcium influx Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                        2667 Non-coding RNA expression,alteration Activation, inflammation pathway Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                        2668 Non-coding RNA expression,alteration Oxidative Stress Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                        2670 Non-coding RNA expression,alteration Fibroblast proliferation and differentiation Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                        2671 Non-coding RNA expression,alteration Apoptosis Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                        2672 Non-coding RNA expression,alteration Dysfunctional autophagy Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                        3203 Non-coding RNA expression,alteration EMT May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                        2414 inflammasome activity, increased Hyperinflammation Jun 25, 2021 Jun 25, 2021
                                                                                                                                                                                                                                                                                        • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                        1556 NFE2/Nrf2 repression Reduced, FXR activity Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                        • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                        2979 NFE2/Nrf2 repression Increase, Oxidative Stress Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                        2984 NFE2/Nrf2 repression Activation, HIF1α Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                        3035 NFE2/Nrf2 repression Activation, inflammation pathway Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                        2457 Neutrophil activation, Increased Platelet-neutrophil interactions, Increased Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                        • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                        210 Neuronal dysfunction Neuroinflammation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                          2941 Neuronal dysfunction Neurological disorder Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                          • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                          208 Neuroinflammation N/A, Neurodegeneration Nov 29, 2016 Feb 23, 2021
                                                                                                                                                                                                                                                                                          • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                          • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                          759 Neuroinflammation Synaptogenesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                            906 Neuroinflammation Degeneration of dopaminergic neurons of the nigrostriatal pathway Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                            • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                            1687 Neuroinflammation Cell injury/death Nov 9, 2017 Nov 7, 2019
                                                                                                                                                                                                                                                                                            • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                            2288 Neuroinflammation Encephalitis Feb 23, 2021 Feb 23, 2021
                                                                                                                                                                                                                                                                                            • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                                            2500 Neuroinflammation Neuronal network function, Decreased Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                            • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                            2717 Neuroinflammation Increase, Cell death Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                              1803 Reduced neural crest cell migration Reduced collagen production Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                              • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                              2563 Reduced neural crest cell migration Transposition of the great arteries Feb 8, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                              • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                              1789 Necrotic Tissue Liver Injury Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                              • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                              • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                              3148 narcosis Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                              • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                              324 N/A, Unknown Proliferation, Cell proliferation in the absence of cytotoxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                                                                                              751 N/A, Unknown Increased, Kidney Failure Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Kidney toxicity induced by activation of 5HT2C
                                                                                                                                                                                                                                                                                              650 N/A, sedation Decreased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                              242 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Altered regulation, Alpha hemoglobin Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                              243 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Formation, Formation of hemoglobin adducts Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                              244 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Propagation, Oxidative stress Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                              245 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leadin Damaging, Red blood cells; hemolysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                              • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                              207 N/A, Neurodegeneration Neuroinflammation Nov 29, 2016 Jun 13, 2018
                                                                                                                                                                                                                                                                                              • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                              • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                              368 N/A, Neurodegeneration Neuronal network function, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                647 N/A, Neurodegeneration Decreased, Neuronal network function in adult brain Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                1069 N/A, Neurodegeneration Impairment, Learning and memory Nov 29, 2016 Apr 11, 2024
                                                                                                                                                                                                                                                                                                • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                                • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                2287 N/A, Neurodegeneration Encephalitis Feb 23, 2021 Feb 23, 2021
                                                                                                                                                                                                                                                                                                • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                3070 N/A, Neurodegeneration Overactivation, NMDARs Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                3075 N/A, Neurodegeneration impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                3081 N/A, Neurodegeneration Increase, seizure Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                182 N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number N/A, Cyanosis occurs Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                2889 N/A, Liver Steatosis Cell injury/death Apr 13, 2023 Apr 13, 2023
                                                                                                                                                                                                                                                                                                  168 N/A, Interferences with SH-/selen-proteins Depletion, GSH Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                    593 N/A, hypoxia Increased, amputations Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                    • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                    996 N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects Alterations, Cellular proliferation / hyperplasia Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                    • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                                                                                                                                                                                                                    136 N/A, Gap Reduction, Ca and HCO3 transport to shell gland Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                    88 N/A, Covalent binding to protein, possibly lysine residue Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways Nov 29, 2016 Sep 24, 2020
                                                                                                                                                                                                                                                                                                      1700 N/A, Covalent binding to protein, possibly lysine residue Activation, Dendritic Cells Dec 7, 2017 Sep 24, 2020
                                                                                                                                                                                                                                                                                                        757 N/A, Ataxia, paralysis, or hyperactivity Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                        • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                        33 N/A, Androgen receptor, Antagonism Altered, Transcription of genes by the AR Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                        • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                        35 N/A, Androgen receptor, Antagonism Alteration, Wnt pathway Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                        • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                        2445 Mucus Viscosity, Increased CBF, Decreased Jul 19, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                          2446 Mucus Viscosity, Increased MCC, Decreased Jul 19, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                            2443 MCC, Decreased Decreased lung function Jul 19, 2021 Mar 24, 2023
                                                                                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                            • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                            1563 Mu Opioid Receptor Agonism Release of G Proteins Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                                                                            • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                                                                            • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                            2448 Motile Cilia Number/Length, Decreased CBF, Decreased Jul 23, 2021 Sep 28, 2021
                                                                                                                                                                                                                                                                                                            • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                            802 modulation, Unknown Increased, HIF-1 alpha transcription Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                            • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                            603 modulation, sodium channel prolonged, Depolarization of neuronal membrane Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                            • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                            1941 Mitochondrial Injury Increased reactive oxygen species (in the mitochondria) Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                              1942 Mitochondrial Injury Impaired, Proteostasis Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                2715 Mitochondrial Injury Increase, Cell death Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                  3049 Mitochondrial Injury Increase, Cyt c release Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                  • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                  2193 Mitochondrial dysfunction EMPTY Apoptotic cell death Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                    2195 Mitochondrial dysfunction EMPTY ER stress Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                      2499 Mitochondrial dysfunction EMPTY Oxidative Stress Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                      • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                      2932 Mitochondrial dysfunction EMPTY Impaired insulin signaling May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                        3043 Mitochondrial dysfunction EMPTY Proteasomal dysfunction Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                          363 Mitochondrial dysfunction Cell injury/death Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                          • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                          • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                          • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                          582 Mitochondrial dysfunction Neuronal network function, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                          660 Mitochondrial dysfunction Overwhelmed, Mitochondrial DNA repair mechanisms Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                          664 Mitochondrial dysfunction impaired, Thoracic shivering Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                            904 Mitochondrial dysfunction Impaired, Proteostasis Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                            • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                            908 Mitochondrial dysfunction Degeneration of dopaminergic neurons of the nigrostriatal pathway Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                            • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                            1152 Mitochondrial dysfunction impaired, Hive thermoregulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                            1154 Mitochondrial dysfunction Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                            1311 Mitochondrial dysfunction Altered, Ca2+-calmodulin activated signal transduction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                            1684 Mitochondrial dysfunction Oxidative Stress Nov 9, 2017 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                            1958 Mitochondrial dysfunction Increased reactive oxygen species (in the mitochondria) Jun 15, 2019 Jun 15, 2019
                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                            2224 Mitochondrial dysfunction Increase, ROS production Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                            • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                            2227 Mitochondrial dysfunction Increase, ROS Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                            • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                            2228 Mitochondrial dysfunction Decrease, ATP pool Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                            • Thermal stress leading to population decline (1)
                                                                                                                                                                                                                                                                                                                            2822 Mitochondrial dysfunction Decrease, Mitochondrial ATP production Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                            • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                            • Renal protein alkylation leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                            3131 Mitochondrial dysfunction Increase, Apoptosis Feb 21, 2024 Feb 21, 2024
                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                            3132 Mitochondrial dysfunction increased,Vascular endothelial dysfunction Feb 21, 2024 Feb 21, 2024
                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                            • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                            3134 Mitochondrial dysfunction Increase, Cytotoxicity (renal tubular cell) Feb 28, 2024 Mar 6, 2024
                                                                                                                                                                                                                                                                                                                            • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                            • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                            3136 Mitochondrial dysfunction Proteasomal dysfunction Feb 29, 2024 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                            3141 Mitochondrial dysfunction Increased, Reactive oxygen species Mar 6, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                            • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                            3146 Mitochondrial dysfunction Apoptosis Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                            • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                            3149 Mitochondrial dysfunction Necrosis Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                            3150 Mitochondrial dysfunction cell injury Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                            3152 Mitochondrial dysfunction Apoptotic cell death Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                            3153 Mitochondrial dysfunction ER stress Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                            3155 Mitochondrial dysfunction Occurrence, Cytoplasmic vacuolization (hepatocyte) Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                            3156 Mitochondrial dysfunction Occurrence, Ballooning degeneration (hepatocyte) Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                            3157 Mitochondrial dysfunction Occurrence, Cytoplasmic vacuolization (kupffer cell) Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                            3158 Mitochondrial dysfunction Occurrence, Cytoplasmic vacuolization (Bile duct cell) Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                            3161 Mitochondrial dysfunction Impaired insulin signaling Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                            3164 Mitochondrial dysfunction Altered expression of NRF2 pathway-dependent genes Mar 14, 2024 Mar 14, 2024
                                                                                                                                                                                                                                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                            3165 Mitochondrial dysfunction Inhibition, Nuclear factor kappa B (NF-kB) Mar 14, 2024 Mar 14, 2024
                                                                                                                                                                                                                                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                            1783 Mitochondrial Complex V inhibition Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                            1786 Mitochondrial Complex V inhibition Increased reactive oxygen species (in the mitochondria) Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                              1782 Mitochondrial Complex IV inhibition Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                              • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                              1785 Mitochondrial Complex IV inhibition Increased reactive oxygen species (in the mitochondria) Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                1780 Mitochondrial Complex I inhibition Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                  1790 Mitochondrial Complex I inhibition Increased reactive oxygen species (in the mitochondria) Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                    402 Metabolism of AFB1, Production of Reactive Electrophiles Formation, Pro-mutagenic DNA Adducts Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                    • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                    808 malformed, Male reproductive tract Decrease, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                    • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                    405 Malformation, Male reproductive tract impaired, Fertility Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                    • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                    2807 Loss of drebrin Dysfunctional synapses Dec 11, 2022 Dec 11, 2022
                                                                                                                                                                                                                                                                                                                                    • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                    1972 Loss of barrier function Blood extravasation into the lungs Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                      1705 Loss of alveolar capillary membrane integrity Activation of Th2 cells Jan 5, 2018 May 16, 2023
                                                                                                                                                                                                                                                                                                                                      • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                      2174 Loss of alveolar capillary membrane integrity Blood extravasation into the lungs Oct 22, 2020 Oct 22, 2020
                                                                                                                                                                                                                                                                                                                                        2258 Loss of alveolar capillary membrane integrity Impaired lung function Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                          2259 Loss of alveolar capillary membrane integrity Substance - LS interaction Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                            2368 Loss of alveolar capillary membrane integrity Inhibition of LS function. Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                            • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                            2369 Loss of alveolar capillary membrane integrity Reduced tidal volume Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                            • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                            2372 Loss of alveolar capillary membrane integrity Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                            • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                            1500 Locomotor activity, decreased Decreased, Reproductive Success May 8, 2017 Jun 26, 2017
                                                                                                                                                                                                                                                                                                                                            • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                            1728 Lipid Peroxidation Protein Adduct Formation Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                            • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                            1731 Lipid Peroxidation General Apoptosis Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                            • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                            1778 Leukocyte recruitment/activation Activation, Stellate cells Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                            • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                            1901 Leukocyte recruitment/activation Increase, Cell Proliferation (Epithelial Cells) May 7, 2019 May 7, 2019
                                                                                                                                                                                                                                                                                                                                              1905 Leukocyte recruitment/activation Increase in RONS May 7, 2019 May 9, 2019
                                                                                                                                                                                                                                                                                                                                              • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                              • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                              2891 Leukocyte recruitment/activation Increased extracellular matrix deposition Apr 13, 2023 Apr 13, 2023
                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                              2152 TGFbeta expression Activation, TGF-beta pathway Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                              • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                              983 Increase, Vascular Resistance Hypertension Nov 29, 2016 Oct 13, 2017
                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                              982 Impaired, Vasodilation Increase, Vascular Resistance Nov 29, 2016 Oct 13, 2017
                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                              958 Depletion, Nitric Oxide Impaired, Vasodilation Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                              988 Decrease, AKT/eNOS activity Depletion, Nitric Oxide Nov 29, 2016 Oct 16, 2017
                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                              956 Uncoupling, eNOS Depletion, Nitric Oxide Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                              3014 Uncoupling, eNOS Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                3023 Uncoupling, eNOS increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                953 Decrease, Tetrahydrobiopterin Uncoupling, eNOS Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                952 Decrease, GTPCH-1 Decrease, Tetrahydrobiopterin Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                955 S-Glutathionylation, eNOS Uncoupling, eNOS Nov 29, 2016 Oct 12, 2017
                                                                                                                                                                                                                                                                                                                                                • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                1774 Irritation induced sneezing Increased Airway Hyper-responsiveness,Cough, Dyspnea Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                  1167 Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                  • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                  393 irregularities, ovarian cycle Decrease, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                    394 irregularities, ovarian cycle impaired, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                    • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                                                                                                                                                                                                                    • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                    2490 Disruption of the intestinal barrier Recruitment of inflammatory cells Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                      2494 Disruption of the intestinal barrier GI disorders Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                        2495 Disruption of the intestinal barrier Hyperinflammation Oct 19, 2021 Feb 8, 2023
                                                                                                                                                                                                                                                                                                                                                          1118 interruption, Ovulation Increased, circulating estrogen levels Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                          • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                          2497 IFN-I response, antagonized SARS-CoV-2 production Oct 24, 2021 Dec 14, 2023
                                                                                                                                                                                                                                                                                                                                                          • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                          • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                          • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                          • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                          • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                          1017 Interference, nuclear localization of NFAT Reduction, NFAT/AP-1 complex formation Nov 29, 2016 Jul 2, 2021
                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                          1836 Interaction of α-diketones with arginine residues Proteasomal dysfunction Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                          • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                          3178 Insulin resistance, increased Metabolically unhealthy Obesity Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                          • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                          3180 Insulin resistance, increased Metabolic syndrome Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                          • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                          329 Insufficiency, Vascular Abnormal, Morphogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                            1036 Insufficiency, Vascular Increased, Developmental Defects Nov 29, 2016 Jan 18, 2022
                                                                                                                                                                                                                                                                                                                                                            • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                            2702 Activation, IP3R Increased, Intracellular Calcium overload Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                            3037 Activation, IP3R Increased, glutamate Sep 8, 2023 Sep 8, 2023
                                                                                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                            1382 Inhibition, Wnt pathway Defect of Embryogenesis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                            • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                                                                                                                                                            335 Inhibition, VegfR2 Reduction, Angiogenesis Nov 29, 2016 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                            • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                            867 Inhibition, UROD Oxidation, Uroporphyrinogen Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                              1070 Inhibition, UROD Accumulation, Highly carboxylated porphyrins Nov 29, 2016 May 30, 2018
                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                              585 Inhibition, sodium channel Decreased, Sodium conductance 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                              • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                              590 Inhibition, sodium channel Increased, Atrioventricular block and bradycardia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                1242 Inhibition, sodium channel Decreased, sodium conductance 2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                716 Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme Increased, Induction of pyruvate dehydrogenase (PDH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                799 Inhibition, Prolyl hydroxylases Increased, HIF-1 heterodimer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                511 Inhibition, PPAR alpha Inhibition, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                836 Inhibition, Phospholipase A Damage, Lipid bilayer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                837 Inhibition, Phospholipase A Disturbance, Lysosomal function Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                3154 Inhibition, Phospholipase A Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                1202 Inhibition, Pendrin TH synthesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Pendrin inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                1131 Inhibition, organic anion transporter 1 (OAT1) Increased, blood uric acid concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                387 Inhibition, Nuclear factor kappa B (NF-kB) Suppression, Inflammatory cytokines Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                1828 Inhibition, Nuclear factor kappa B (NF-kB) Activation, Caspase 8 pathway Jan 7, 2019 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                1871 Inhibition, Nuclear factor kappa B (NF-kB) Impairment of TDAR Mar 12, 2019 Mar 12, 2019
                                                                                                                                                                                                                                                                                                                                                                  1921 Inhibition, Nuclear factor kappa B (NF-kB) Impaired T cell activation May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                    2003 Inhibition, Nuclear factor kappa B (NF-kB) Suppression of T cell activation Nov 17, 2019 Mar 2, 2023
                                                                                                                                                                                                                                                                                                                                                                    • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                    2306 Inhibition, Nuclear factor kappa B (NF-kB) Increased proinflammatory mediators Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                      2644 Inhibition, Nuclear factor kappa B (NF-kB) Increase in inflammation Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                      • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                      213 Inhibition, NMDARs Decreased, Calcium influx Nov 29, 2016 Apr 7, 2018
                                                                                                                                                                                                                                                                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                                                                                                      214 Inhibition, NMDARs Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                        215 Inhibition, NMDARs Neuronal dysfunction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                          3124 Inhibition, NMDARs Aberrant, synaptic formation and plasticity Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                          • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                          3241 Inhibition, NFAT Increased, activation of RAAS Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                            3242 Inhibition, NFAT Inhibition, COX-2 activity Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                            934 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Mitochondrial dysfunction Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                            1809 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Decrease, OXPHOS Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                            1940 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Decrease in mitochondrial oxidative phosphorylation Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                            442 Inhibition, Na+/I- symporter (NIS) Thyroidal Iodide, Decreased Nov 29, 2016 May 29, 2018
                                                                                                                                                                                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                            552 Inhibition, Na+/I- symporter (NIS) TH synthesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                            • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                            1503 Inhibition, Na+/I- symporter (NIS) Impairment, Learning and memory May 10, 2017 Apr 4, 2019
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                            2232 Inhibition, Na+/I- symporter (NIS) T4 in serum, Decreased Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                            • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                            1049 Inhibition, Motor neuron activity Induction, Somatic muscle paralysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              475 Inhibition, Mitochondrial fatty acid beta-oxidation Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                              • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                              538 Inhibition, Mitochondrial fatty acid beta-oxidation Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                              2565 Inhibition, ETC complexes of the respiratory chain Increase, Oxidative Stress Feb 8, 2022 Mar 7, 2022
                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                              2636 Inhibition, ETC complexes of the respiratory chain Decrease, MMP Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                              2821 Inhibition, ETC complexes of the respiratory chain Mitochondrial dysfunction Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                                                                              • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                                                                              1413 Inhibition, LXR Inhibition, PPAR alpha Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                1197 Inhibition, Iodotyrosine deiodinase (IYD) Thyroidal Iodide, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                2476 Inhibition, Iodotyrosine deiodinase (IYD) T4 in serum, Decreased Sep 9, 2021 Sep 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                159 Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307 Induction, Sustained Hepatotoxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                1827 Inhibition, IKK complex Inhibition, Nuclear factor kappa B (NF-kB) Jan 7, 2019 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                804 Inhibition, HMG-CoA reductase Decreased, mevalonate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                519 Inhibition, FoxA2 Down Regulation, CPT1A Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                523 Inhibition, FoxA2 Down Regulation, HMGCS2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                2080 Inhibition, Fin regeneration Reduced, Swimming performance Apr 21, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                1056 Inhibition, Feeding Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                3087 Inhibition, Feeding Increase, Mortality Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                1692 Inhibition of fatty acid beta oxidation Increase, cytosolic fatty acid Nov 13, 2017 Nov 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                597 Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel Decreased, Sodium conductance 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                3121 inhibition, EKR1/2 signaling pathway Aberrant, synaptic formation and plasticity Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                1203 Inhibition, Dual oxidase TH synthesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                1200 Inhibition, Deiodinase 3 Increased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                1026 Inhibition, Deiodinase 2 Decreased, Triiodothyronine (T3) Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                1042 Inhibition, Deiodinase 2 Reduced, Posterior swim bladder inflation Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                1043 Inhibition, Deiodinase 2 Reduced, Anterior swim bladder inflation Nov 29, 2016 Mar 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                  1199 Inhibition, Deiodinase 2 Decreased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                  • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                  1037 Inhibition, Deiodinase 1 Decreased, Triiodothyronine (T3) Nov 29, 2016 Oct 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                  • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                  • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                  1044 Inhibition, Deiodinase 1 Reduced, Posterior swim bladder inflation Nov 29, 2016 Oct 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                  • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                  1045 Inhibition, Deiodinase 1 Reduced, Anterior swim bladder inflation Nov 29, 2016 Mar 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                    1198 Inhibition, Deiodinase 1 Decreased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                    1878 Inhibition of Cyp17A1 activity Reduction, DHEA Apr 10, 2019 Apr 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                    1879 Inhibition of Cyp17A1 activity Reduction, androstenedione Apr 10, 2019 Apr 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                    95 Inhibition, Cyclooxygenase activity Reduction, Prostaglandin E2 concentration Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                    670 Inhibition, Cyclooxygenase activity Reduced, Prostaglandin F2alpha synthesis, ovary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                    681 Inhibition, Cyclooxygenase activity Decreased, Prostaglandin F2alpha synthesis, ovary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                    686 Inhibition, Cyclooxygenase activity Reduced, Prostaglandins, ovary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                    689 Inhibition, Cyclooxygenase activity Reduced, Prostaglandin E2 concentration, hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                    1137 Inhibition, Cyclooxygenase 1 activity Decreased, Prostaglandin F2alpha concentration, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                    3239 Inhibition, COX-2 activity Increased, activation of RAAS Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                    2172 Inhibition, Chitobiase Decrease, Digestion of old cuticle Oct 21, 2020 Oct 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                    • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                    2170 Inhibition, Chitinase Decrease, Digestion of old cuticle Oct 21, 2020 Oct 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                    • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                    1742 Inhibition, CHS-1 Decrease, Cuticular chitin content May 24, 2018 Feb 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                    • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                    • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                    1015 Inhibition, Calcineurin Activity Activation, Suppression of NFAT activation and hindrance of nuclear localization Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                      1254 Inhibition, Calcineurin Activity Suppression, IL-2 and IL-4 production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                        1508 Inhibition, Calcineurin Activity Interference, nuclear localization of NFAT May 19, 2017 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                        3237 Inhibition, Calcineurin Activity Increased, activation of RAAS Jun 6, 2024 Jun 6, 2024
                                                                                                                                                                                                                                                                                                                                                                                          3238 Inhibition, Calcineurin Activity Inhibition, COX-2 activity Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                                            3240 Inhibition, Calcineurin Activity Inhibition, NFAT Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                            61 Inhibition, Ca++ ATPase Increase, Ca++ (intracellular) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                            • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                            927 Inhibition, Bile Salt Export Pump (ABCB11) Bile accumulation, Pathological condition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                            • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                            45 Inhibition, Aromatase Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Nov 30, 2016
                                                                                                                                                                                                                                                                                                                                                                                            • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                            1767 Inhibition, Aromatase Altered regulation, Alpha hemoglobin Sep 13, 2018 Sep 13, 2018
                                                                                                                                                                                                                                                                                                                                                                                              2144 Inhibition, Aromatase Reduction, E2 Synthesis by the undifferentiated gonad Jun 15, 2020 Jul 11, 2022
                                                                                                                                                                                                                                                                                                                                                                                              • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                              2167 Inhibition, Aromatase Increased, Differentiation to Testis Jul 28, 2020 Dec 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                              • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                              2350 Inhibition, Aromatase Increased, Male Biased Sex Ratio Apr 13, 2021 Jan 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                              • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                              2079 Inhibition, Activin signaling Inhibition, Fin regeneration Apr 21, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                              • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                              792 Inhibition, 5α-reductase activity Decrease, Bioactivation of testosterone Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                3226 Inhibition, 5α-reductase activity Decrease, testosterone levels May 24, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                1880 Inhibition, 5α-reductase Decrease, DHT level Apr 18, 2019 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                                                                                                                                                                                                                                                                • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                635 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, serotonin (5-HT) 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                  643 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, serotonin (5-HT) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                  1208 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, cilia movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                    1316 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, muscular waves in foot Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                    1317 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, valve movement Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                    1318 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increase, cilia movement Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                    1319 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) increased mantel display Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                    1337 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Increased, oocyte maturation Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                    775 Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme Increased, Plasma tyrosine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                    • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                    3016 Inhibition VEGF/VEGFR pathway Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                      3025 Inhibition VEGF/VEGFR pathway increased,Vascular endothelial dysfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                      • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                      1891 tyrosinase Reduction of L-Dopaquinone May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                      2974 SULT1E1 inhibition Increased, estrogens Jul 28, 2023 Jul 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                      • SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
                                                                                                                                                                                                                                                                                                                                                                                                      2851 Inhibition of rapid delayed rectifying potassium current Prolongation of Action Potential Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                      • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                      2403 Inhibition of Plxna2 Overexpression of rasl11b May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                      1570 Inhibition of neurotransmitter release Analgesia Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                      1573 Inhibition of neurotransmitter release Anti-depressant Activity Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                      1569 Inhibition of Ca Channels Inhibition of neurotransmitter release Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                      • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                      1864 Inhibition of N-linked glycosylation Accumulation, misfolded proteins Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                      1673 Inhibition, mitochondrial DNA polymerase gamma (Pol gamma) Depletion, mtDNA Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                      1950 MTHFR inhibition Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                        1951 Methionine synthase Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                          1637 Inhibition of lysyl oxidase Reduction of collagen crosslinking Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                          1969 Inhibition of LS function. Alveolar collapse Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                          • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                          2255 Inhibition of LS function. Loss of alveolar capillary membrane integrity Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                            2256 Inhibition of LS function. Reduced tidal volume Jan 8, 2021 Jan 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                              2370 Inhibition of LS function. Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                              • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                              2024 Inhibition of JAK3 STAT5 inhibition Jan 5, 2020 Nov 3, 2021
                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                              2539 Inhibition of Ikr Prolongation of Action Potential Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                2402 Inhibition of Fyna Inhibition of Plxna2 May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                3245 inhibition of E4 (Uracil-DNA Glycosylase) Recruitment of inflammatory cells Jun 10, 2024 Jun 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                1949 CBS inhibition Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                2694 Inhibition CerS Reduced complex sphingolipids Jul 19, 2022 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                2697 Inhibition CerS Increased S1-P Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                1952 betaine-homocysteine methyltransferase inhibition Homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                  2401 ALDH1A (RALDH), inhibition Decreased, atRA concentration May 24, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                  2162 Inhibition of 11β-HSD Decreased, 11KT Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                  2707 Inhibition, GABAAr Increase, Cell membrane depolarization Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                  • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                  1520 Inhibit, serotonin transporter activity Decreased, serotonin transporter activity May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                    3053 IAV production increased IAV budding Oct 3, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                    3030 IAV cell entry immune mechanisms antagonized Aug 23, 2023 Aug 23, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                    3055 IAV budding infection proliferation Oct 3, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                    2978 IAV binds receptor IAV cell entry Aug 11, 2023 Jan 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                    1855 Inflammatory events Eczematous eruption Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                      2916 Inflammatory events Increased, Invasion May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                      2917 Inflammatory events prostatic intraepithelial neoplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                      926 Infiltration, Inflammatory cytokines Inflammation, Liver Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                        916 Infiltration, Inflammatory cells Inflammation, Liver Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          2235 Induction, Upregulation of glucuronyltransferase activity Increase, Biliary excretion TH glucuronide Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                            2428 Induction, Upregulation of glucuronyltransferase activity Increased, T4/T3 catabolism Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                              2478 Induction, Upregulation of glucuronyltransferase activity Increased, Clearance of thyroxine from serum Sep 10, 2021 Sep 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                              • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                              • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                              • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                              • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                              2483 Induction, Upregulation of glucuronyltransferase activity T4 in serum, Decreased Sep 14, 2021 Sep 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                2884 Induction, Upregulation of glucuronyltransferase activity Increase, Glucuronidation of T4 Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                  299 Induction, Sustained Hepatotoxicity Induction, Sustained Cell Proliferation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                  298 Induction, Sustained Cell Proliferation Formation, Liver tumor Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                  1050 Induction, Somatic muscle paralysis Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                  1055 Induction, Somatic muscle paralysis Inhibition, Feeding Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                  3089 Induction, Somatic muscle paralysis Increased, Neuronal synaptic inhibition Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                  261 Induction, Pre-mature molting Decrease, Fecundity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    262 Induction, Pre-mature molting Increase, Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                      263 Induction, Pre-mature molting Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        1059 Induction, pharyngeal muscle paralysis Inhibition, Feeding Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                        1518 Sustained proliferation Liver Cancer May 30, 2017 Oct 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                        859 Induction, Microvesicular fat Formation, Liver fibrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                        1263 Induction, Male reproductive tract Increased, Male offspring Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                        170 Induction, Liver “Dysfunctional” Changes by CGA 330050 Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                        386 Induction, IKB inhibitory protein Inhibition, Nuclear factor kappa B (NF-kB) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                                                                                        1262 Induction, Doublesex1 gene Induction, Male reproductive tract Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                        868 Induction, CYP1A2/CYP1A5 Oxidation, Uroporphyrinogen Nov 29, 2016 May 31, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                        2893 Induction, CYP1A2/CYP1A5 Increase, ROS production Apr 13, 2023 Apr 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          2907 Induction, CYP1A2/CYP1A5 Increase, Oxidative Stress May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                          70 Induction, Chitin degradation and resorption Induction, Pre-mature molting Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            1630 Cell damage sensing Sustained inflammatory cytokine release Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                              1631 Cell damage sensing Increase, ROS production Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                1632 Cell damage sensing Increased, secretion of local growth factors Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                  2538 Induction of hERG trafficking defects Inhibition of Ikr Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                    2021 Induction of GATA3 expression Increase of Th2 cells producing IL-4 Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                    1221 induced, parturition Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                      1961 dysfunction of microcirculation anterior-posterior axis development Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                      2512 dysfunction of microcirculation Increased inflammatory immune responses Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                        2295 Induced, Angiotensin (Ang) II accumulation Impaired gustatory nerve Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                          2322 Induced, Angiotensin (Ang) II accumulation Increased Ang II type 1 receptor (AT1R) Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                            2520 Induced, Angiotensin (Ang) II accumulation Hyperactivation of ACE/Ang-II/AT1R axis Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1324 induced spawning Decreased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1325 induced spawning Increased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1323 Induced parturition Decreased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1326 Induced parturition Increased, Reproductive Success Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                2065 ACE2 enzymatic inhibition Increased AngII Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                2321 ACE2 enzymatic inhibition Induced, Angiotensin (Ang) II accumulation Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2434 ACE2 enzymatic inhibition Increase plasma Ang II Jul 13, 2021 Jul 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1622 Sustained inflammatory cytokine release Increased, secretion of local growth factors Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1633 Sustained inflammatory cytokine release Differentiation of fibroblasts Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2526 Increases in cellular ROS Porcupine-induced Wnt secretion and Wnt signaling activation Oct 31, 2021 Apr 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2982 increased,Vascular endothelial dysfunction Angiogenesis disfunction Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3019 increased,Vascular endothelial dysfunction Impaired Platelet Aggregation Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3027 increased,Vascular endothelial dysfunction Vascular barrier disruption Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3031 increased,Vascular endothelial dysfunction Angiogenesis dysfunction Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2855 Increased,Cardiac dysfunction Increased Mortality Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1175 Increased, water retention in foot Increased, foot detachment Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1223 Increased, water retention in foot Increased, valve movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1224 Increased, water pumping Increased, water retention in foot Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1225 Increased, water pumping premature, Spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1226 Increased, water pumping induced, parturition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                571 Increased, Viral susceptibility impaired, Development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                575 Increased, Viral susceptibility Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1173 Increased, valve movement Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1174 Increased, valve movement Increased, water retention in foot Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1216 Increased, valve movement Increased, water pumping Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1227 Increased, valve movement Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1320 Increased, valve movement induced spawning Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1334 Increased, valve movement Induced parturition Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2579 tumor growth N/A, Breast Cancer Feb 15, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3139 tumor growth Metastasis, Breast Cancer Mar 5, 2024 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1201 Increased, Triiodothyronine (T3) in tissues Altered, Amphibian metamorphosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2243 Increased, Triiodothyronine (T3) in tissues Altered, TH-dependent gene expression Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      486 Increased, Triglyceride formation Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2241 Increased, Thyroxine (T4) in serum Altered, Amphibian metamorphosis Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2242 Increased, Thyroxine (T4) in serum Altered, TH-dependent gene expression Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1066 Increased, Thyroid-stimulating hormone (TSH) Increased, Hypertrophy and proliferation (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2240 Increased, Thyroid-stimulating hormone (TSH) Increased, Thyroxine (T4) in serum Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2424 Increased, Thyroid-stimulating hormone (TSH) Increase, Hypertrophy and proliferation (follicular cell) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2425 Increased, Thyroid-stimulating hormone (TSH) Increase, Thyroid-stimulating hormone (TSH) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1064 Increased, T4/T3 catabolism Decreased, serum T4/T3 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2423 Increased, T4/T3 catabolism T4 in serum, Decreased Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1527 Increased, synaptic release Increased, extracellular serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              296 Increased, Structural malformations Increased, Lethality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2582 Increased, Steroidogenic acute regulatory protein (StAR) Increased, estrogens Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                813 Increased, Serum creatinine Occurrence, Cytoplasmic vacuolization (Renal tubule) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                814 Increased, Serum creatinine Occurrence, Cystic dilatation (renal tubule) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                816 Increased, Serum creatinine Occurrence, Cytoplasmic vacuolization (podocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1524 Increased, serotonin transporter activity Increased, intracellular serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1528 Increased, serotonin transporter activity Decreased, extracellular serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                636 Increased, serotonin (5-HT) 1 Increase, cilia movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  640 Increased, serotonin (5-HT) 1 Increased, muscular waves in foot Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1172 Increased, serotonin (5-HT) 1 Increased, valve movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1186 Increased, serotonin (5-HT) 1 Decreased, gametogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1189 Increased, serotonin (5-HT) 1 Increased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1192 Increased, serotonin (5-HT) 1 increased or inappropriate, mantel display Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            644 Increased, serotonin (5-HT) Decreased, anxiety Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1207 Increased, serotonin (5-HT) Increased, mantel display Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1209 Increased, serotonin (5-HT) Increased, cilia movement Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1212 Increased, serotonin (5-HT) Increased, oocyte maturation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1327 Increased, serotonin (5-HT) Increased, valve movement Jan 17, 2017 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1332 Increased, serotonin (5-HT) Increased, muscular waves in foot Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1333 Increased, serotonin (5-HT) Increase, cilia movement Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1336 Increased, serotonin (5-HT) increased mantel display Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1550 Increased, seizure Increased, epilepsy Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1703 Increased proinflammatory mediators Recruitment of inflammatory cells Jan 5, 2018 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2053 Increased proinflammatory mediators Increased transcription of genes encoding acute phase proteins Mar 1, 2020 Dec 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2061 Increased proinflammatory mediators Increased inflammatory immune responses Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2301 Increased proinflammatory mediators Impaired gustatory nerve Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2307 Increased proinflammatory mediators Accumulation, Collagen Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2651 Increased proinflammatory mediators Activation, Dendritic Cells Apr 28, 2022 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3052 Increased proinflammatory mediators Systemic acute phase response Sep 19, 2023 Dec 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1074 Increased, secretion of local growth factors Increased, proliferation of mesenchymal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1075 Increased, secretion of local growth factors Increased, IGF-1 (mouse) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1129 Increased, secretion of local growth factors Increased, Cell Proliferation (mesothelium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1624 Increased, secretion of local growth factors Differentiation of fibroblasts Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1625 Increased, secretion of local growth factors EMT Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1092 Increased, secretion of LH from anterior pituitary Hyperplasia, ovarian stromal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2581 Increased, secretion of LH from anterior pituitary Increased, Steroidogenic acute regulatory protein (StAR) Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1088 Increased, secretion of GnRH from hypothalamus Increased, secrection of FSH from anterior pituitary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1089 Increased, secretion of GnRH from hypothalamus Increased, secretion of LH from anterior pituitary Nov 29, 2016 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1090 Increased, secrection of FSH from anterior pituitary Hyperplasia, ovarian stromal cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1091 Increased, secrection of FSH from anterior pituitary Hyperplasia, ovarian epithelium Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1308 Increased, Second Messenger Production Increased, Non-genomic signaling Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1215 Increased, Reproductive Success Increased, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1704 Recruitment of inflammatory cells Loss of alveolar capillary membrane integrity Jan 5, 2018 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1964 Recruitment of inflammatory cells Increased, Reactive oxygen species Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2354 Recruitment of inflammatory cells Hyperinflammation Apr 20, 2021 Feb 8, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2491 Recruitment of inflammatory cells Disruption of the intestinal barrier Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2492 Recruitment of inflammatory cells GI disorders Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2543 Recruitment of inflammatory cells Gut dysbiosis Dec 15, 2021 Dec 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2658 Recruitment of inflammatory cells Increase, Cytotoxicity (epithelial cells) May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2761 Recruitment of inflammatory cells Increased proinflammatory mediators Sep 1, 2022 Sep 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2903 Recruitment of inflammatory cells Increase in inflammation May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3246 Recruitment of inflammatory cells Cardiac Heart Failure Jun 10, 2024 Jun 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1162 Increased, Reactive oxygen species Increased, Oxidative Stress Nov 29, 2016 Jul 31, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1696 Increased, Reactive oxygen species increased, oncotic necrosis Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1965 Increased, Reactive oxygen species Increased, DNA damage and mutation Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2009 Increased, Reactive oxygen species Oxidative Stress Dec 3, 2019 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2033 Increased, Reactive oxygen species β-catenin activation Jan 19, 2020 Jan 19, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2320 Increased, Reactive oxygen species Increased activation, Nuclear factor kappa B (NF-kB) Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2324 Increased, Reactive oxygen species Increased extracellular matrix deposition Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2328 Increased, Reactive oxygen species Increased Sodium-sensitive hypertension Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2460 Increased, Reactive oxygen species Increased, LPO Aug 5, 2021 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2549 Increased, Reactive oxygen species D1 protein deactivation Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2550 Increased, Reactive oxygen species Decrease, MMP Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2594 Increased, Reactive oxygen species Accumulation, Collagen Mar 3, 2022 Mar 3, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2660 Increased, Reactive oxygen species Secondary genotoxicity May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2966 Increased, Reactive oxygen species Apoptosis Jul 18, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3092 Increased, Reactive oxygen species Decreased, PPAR-gamma activation Oct 18, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1463 Increased, RDX dose Activate, GABA-A receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1555 Increased, RDX dose Reduced, GABA-A receptor activation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                343 Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1076 Increased, proliferation of mesenchymal cells Increased, Firbrosarcoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1077 Increased, proliferation of mesenchymal cells Increased, liposarcoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1078 Increased, proliferation of mesenchymal cells Increased, hemagiosarcoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1266 Increased, Proliferation (Endothelial cells) Increased, Angiogenesis Nov 29, 2016 Dec 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1122 Increased, prolactin secretion Increased, hyperplasia (mammary gland) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1114 Increased, prolactin exposure Hyperplasia, Mammary gland Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  595 Increased, predation Reduced, survival Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  654 Increased, predation Decreased, survival Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1095 Increased, PPAR-alpha activation Decreased, bile flow Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1096 Increased, PPAR-alpha activation Increased, cholestasis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1097 Increased, PPAR-alpha activation Alteration, lipid metabolism Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  776 Increased, Plasma tyrosine Increase, Cytotoxicity (corneal cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1960 Plasma HCY level dysfunction of microcirculation Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1526 Increased, packaged serotonin Increased, synaptic release Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1128 Increased, Oxidative Stress Increased, secretion of local growth factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1160 Increased, Oxidative Stress Occurrence, renal proximal tubular necrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1300 Increased, Oxidative Stress Increase, DNA Damage Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2385 Increased, Oxidative Stress Increase, Oocyte apoptosis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2618 Increased, Oxidative Stress Increase, Apoptosis Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2933 Increased, Oxidative Stress Impaired insulin signaling May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2936 Increased, Oxidative Stress Mitochondrial dysfunction EMPTY May 26, 2023 May 26, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3160 Increased, Oxidative Stress Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1213 Increased, oocyte maturation Increased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1328 Increased, oocyte maturation induced spawning Jan 17, 2017 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2633 Increased, Oocyte Atresia Impaired, Reproduction Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1697 increased, oncotic necrosis steatohepatitis Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1295 Increased, Non-genomic signaling Increased, ER binding to T.F. to DNA (non-classical pathway) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1302 Increased, Non-genomic signaling Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1053 Increased, Neuronal synaptic inhibition Increased, Inhibitory postsynaptic potential Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3090 Increased, Neuronal synaptic inhibition Inhibition, Feeding Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      641 Increased, muscular waves in foot Increased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      642 Increased, muscular waves in foot Increased, foot detachment Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1228 Increased, muscular waves in foot Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1306 Increased, Motility Increased, Invasion Nov 29, 2016 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1267 Increased, Migration (Endothelial Cells) Increased, Angiogenesis Nov 29, 2016 Dec 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2575 Increased, Migration (Endothelial Cells) Increase, angiogenesis Feb 15, 2022 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1214 Increased, mantel display Increased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1264 Increased, Male offspring Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2147 Increased, Male Biased Sex Ratio Decrease, Population growth rate Jun 15, 2020 Jan 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Androgen receptor agonism leading to male-biased sex ratio
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          745 Increased, Luteinizing hormone (LH) Increase, Hyperplasia (Leydig cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          638 Increased, locomotion Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1177 Increased, locomotion Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1695 Increased, Liver Steatosis Increased, Reactive oxygen species Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3218 Increased, Liver Steatosis Cell injury/death May 14, 2024 May 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1405 Increased, lipogenesis Increase, cytosolic fatty acid Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1599 Increased, LPO Decrease, Coupling of OXPHOS Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2097 Increased, LPO Decrease, Neutral lipids Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2210 Increased, LPO Increase, Apoptosis Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2222 Increased, LPO Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2464 Increased, LPO Increase, Necrosis Aug 11, 2021 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2879 Increased, LPO impaired, Fertility Apr 5, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3117 Increased, LPO Increased, histomorphological alteration of testis Jan 24, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3231 Increased, LPO Acrolein accumulation Jun 4, 2024 Jun 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  794 Increased, Leutinizing hormone (LH) Increase, Hyperplasia (Leydig cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1544 Increased, leukocyte adherence Increased, leukocyte activation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1545 Increased, leukocyte activation Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  508 Increased, LDL uptake Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1117 Increased, latency period Increased, Adenomas/carcinomas (mammary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1120 Increased, lactotroph hyperplasia and hypertrophy Increased, adenomas (pituitary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2627 Increased, Kisspeptin signalling Decreased, Gonadotropins Apr 5, 2022 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2462 Increased, Kidney Failure Increase, Mortality Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2466 Increased, Kidney Failure Increased Mortality Aug 11, 2021 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2576 Increased, Invasion N/A, Breast Cancer Feb 15, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3138 Increased, Invasion Metastasis, Breast Cancer Mar 5, 2024 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1455 Increased, intracellular sodium (Na+) Activated, voltage-gated sodium channel Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1525 Increased, intracellular serotonin Increased, packaged serotonin Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1465 Increased, intracellular chloride (Cl-) Inactive, membrane depolarization Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      362 Increased, Intracellular Calcium overload Mitochondrial dysfunction Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      892 Increased, Intracellular Calcium overload Decreased, Neuronal network function in adult brain Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1860 Increased, Intracellular Calcium overload Occurrence, Epileptic seizure Feb 13, 2019 Feb 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1862 Increased, Intracellular Calcium overload Cell injury/death Feb 19, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2140 Increased, Intracellular Calcium overload Status epilepticus May 21, 2020 May 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2704 Increased, Intracellular Calcium overload Activation, calpain Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2709 Increased, Intracellular Calcium overload Decrease, OXPHOS Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2710 Increased, Intracellular Calcium overload Endoplasmic reticulum stress Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3042 Increased, Intracellular Calcium overload Mitochondrial dysfunction EMPTY Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3091 Increased, Intracellular Calcium overload Loss of drebrin Oct 18, 2023 Oct 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                547 Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts Increased, Induced Mutations in Critical Genes Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1048 Increased, Inhibitory postsynaptic potential Inhibition, Motor neuron activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1054 Increased, Inhibitory postsynaptic potential Induction, Somatic muscle paralysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1058 Increased, Inhibitory postsynaptic potential Induction, pharyngeal muscle paralysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1127 Increased, inflammation Increased, secretion of local growth factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1063 Increased, induction of UDPGT's in liver Increased, T4/T3 catabolism Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    762 Increased, Induction of pyruvate dehydrogenase (PDH) Increase, Oxidative metabolism Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    342 Increased, Induced Mutations in Critical Genes Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      346 Increased, Induced Mutations in Critical Genes Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 30, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      351 Increased, Induced Mutations in Critical Genes Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        549 Increased, Induced Mutations in Critical Genes Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        891 Increased, Induced Mutations in Critical Genes Increase, Site of Contact Nasal Tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1067 Increased, Hypertrophy and proliferation (follicular cell) Increased, Hyperplasia (follicular cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2427 Increased, Hypertrophy and proliferation (follicular cell) Increase, Hyperplasia (follicular cells) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1123 Increased, hyperplasia (mammary gland) Increased, latency period Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1124 Increased, hyperplasia (mammary gland) Increased, Adenomas/carcinomas (mammary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1107 Increased, Hyperplasia (glandular epithelial cells of endometrium) Increased, adenosquamous carcinomas of endometrium Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1068 Increased, Hyperplasia (follicular cells) Increased Apoptosis, Adenomas/carcinomas (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2426 Increased, Hyperplasia (follicular cells) Increase, Adenomas/carcinomas (follicular cell) Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3118 Increased, histomorphological alteration of testis Impaired, Spermatogenesis Jan 24, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1459 Increased, hippocampal hyperdepolarization Increase, seizure Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1549 Increased, hippocampal hyperdepolarization Increased, seizure Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  800 Increased, HIF-1 heterodimer Decreased, Aromatase (Cyp19a1) mRNA Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  803 Increased, HIF-1 alpha transcription Increased, HIF-1 heterodimer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1206 Increased, Hepatic thyroid hormone uptake/transport Increase, Biliary excretion TH glucuronide Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2237 Increased, Hepatic thyroid hormone uptake/transport T4 in serum, Decreased Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2479 Increased, Hepatic thyroid hormone uptake/transport Increased, Clearance of thyroxine from serum Sep 10, 2021 Sep 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1453 Increased, glutamate Activated, NMDA receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1859 Increased, glutamate Overactivation, NMDARs Feb 13, 2019 Sep 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2861 Increased, glutamate Microglia activation Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2868 Increased, glutamate decreased, Bcl-2 Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2869 Increased, glutamate increased, Bax Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1522 Increased, glucocorticoid receptor activity Reduced, BDNF May 31, 2017 May 31, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2919 Increased, gene expression of AR Increase, Gonadotropins concentration in plasma May 22, 2023 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2247 Increased, Free serum thyroxine (T4) Increased, Hepatic thyroid hormone uptake/transport Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2268 Increased, Free serum thyroxine (T4) Increased, Uptake of thyroxine into tissue Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2272 Increased, Free serum thyroxine (T4) Increased, Clearance of thyroxine from serum Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1176 Increased, foot detachment Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1183 Increased, foot detachment Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1707 Increased cellular proliferation and differentiation Increased extracellular matrix deposition Jan 5, 2018 Dec 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2652 Increased cellular proliferation and differentiation Accumulation, Collagen May 4, 2022 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2263 Increased, Fatty acid uptake Increased, Liver Steatosis Jan 15, 2021 Jan 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            504 Increased, FA Influx Accumulation, Triglyceride Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              505 Increased, FA Influx Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1658 Increased, FA Influx Increased, Triglyceride formation Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1521 Increased, extracellular serotonin Decreased, extracellular serotonin May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1529 Increased, extracellular serotonin Decreased, 5-HT3 Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1531 Increased, extracellular serotonin Activation, 5-HT2A Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1708 Increased extracellular matrix deposition Pulmonary fibrosis Jan 16, 2018 Dec 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2325 Increased extracellular matrix deposition N/A, Liver fibrosis Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3104 Increased, Expression of LXR activated genes Synthesis, De Novo Fatty Acid (FA) Dec 7, 2023 Mar 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2583 Increased, estrogens Increased, circulating estrogen levels Feb 26, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  734 Increased, Estrogen receptor (ER) activity Decreased, Progesterone from corpus luteum Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2737 Increased, Estrogen receptor (ER) activity Increase, Vitellogenin mRNA Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3115 Increased, essential element imbalance Increased, Reactive oxygen species Jan 24, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1251 Increased, ER binding to T.F. to DNA (non-classical pathway) Increase, Cell Proliferation (Epithelial Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1297 Increased, ER binding to T.F. to DNA (non-classical pathway) Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1250 Increased, ER binding to DNA (classical pathway) Increase, Cell Proliferation (Epithelial Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1296 Increased, ER binding to DNA (classical pathway) Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3082 Increased, epilepsy Increase, Mortality Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1157 Increased, Energetic demands and therefore metabolic stress Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nosema infection increases energetic demands leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1252 Increased, Ductal Hyperplasia N/A, Breast Cancer Nov 29, 2016 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1366 Increased, DNA Damage-Repair Apoptosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1966 Increased, DNA damage and mutation Increase, Cell Proliferation Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2417 Increased, DNA damage and mutation Genomic instability Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2608 Increased, DNA damage and mutation Inadequate DNA repair Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2728 Increased, DNA damage and mutation Increase chromosomal aberrations Aug 14, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2146 Increased, Differentiation to Testis Increased, Male Biased Sex Ratio Jun 15, 2020 Jan 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Androgen receptor agonism leading to male-biased sex ratio
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1155 Increased, Deformed Wing Virus levels Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Varroa mite infestation increases virus levels leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  484 Increased, De Novo FA synthesis Increased, Triglyceride formation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    512 Increased, De Novo FA synthesis Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1607 Increased, De Novo FA synthesis Increased, Liver Steatosis Jul 18, 2017 Jul 18, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    695 Increased, cyclic adenosine monophosphate Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      696 Increased, cyclic adenosine monophosphate Reduced, Meiotic prophase I/metaphase I transition, oocyte Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      350 Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2270 Increased, Clearance of thyroxine from serum T4 in serum, Decreased Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1113 Increased, circulating estrogen levels Hyperplasia, Mammary gland Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1119 Increased, circulating estrogen levels Increased, lactotroph hyperplasia and hypertrophy Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2584 Increased, circulating estrogen levels Hyperplasia, ovarian stromal cells Feb 26, 2022 Mar 2, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2585 Increased, circulating estrogen levels Hyperplasia, ovarian epithelium Feb 26, 2022 Mar 2, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1210 Increased, cilia movement premature, Spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1329 Increased, cilia movement induced spawning Jan 17, 2017 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              700 Increased, Chromosome misseggregation Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1100 Increased, cholestasis prolonged, elevation of serun CCK Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1047 Increased, Chloride influx Increased, Inhibitory postsynaptic potential Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                758 Increased, Chloride conductance hyperpolarisation, neuron Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1052 Increased, Chloride conductance Increased, Neuronal synaptic inhibition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1099 Increased, Cellular proliferation / hyperplasia of acinar cells Increased, Pancreatic acinar tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1130 Increased, Cell Proliferation (mesothelium) Increased, mesotheliomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                885 Increased, Catabolism of Muscle Protein Decreased, Body Weight Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                703 Increased, cardiac arrthymia Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1132 Increased, blood uric acid concentration Occurrence, tophi (urate) deposition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1158 Increased, blood uric acid concentration Increased, Oxidative Stress Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1135 Increased, blood potassium concentration Occurrence, cardiac arrthymia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1140 Increased, blood potassium concentration Occurrence, cardiac arrhythmia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  706 Increased, Binding of chemicals to 2u (serum) Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2871 increased, Bax Cell injury/death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2874 increased, Bax Increase, Cell death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    432 Increased, Atrioventricular block and bradycardia Increased Mortality Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      591 Increased, Atrioventricular block and bradycardia Respiratory distress/arrest Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      607 Increased, Ataxia, paralysis, or hyperactivity Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      568 Increased, Appetite and hunger Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3235 Increased, afferent artery vasoconstriction Decreased, Glomerular filtration Jun 6, 2024 Jun 6, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1073 Increased, adipogenesis Increased, secretion of local growth factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1706 Activation of Th2 cells Increased cellular proliferation and differentiation Jan 5, 2018 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3236 Increased, activation of RAAS Increased, afferent artery vasoconstriction Jun 6, 2024 Jun 6, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      146 Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        147 Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Up Regulation, TGFbeta1 expression Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          707 Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) Increase, Cytotoxicity (renal tubular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1445 Increased, 5-HT3 Increased, seizure Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2315 Increased viral transcription and replication Increased proinflammatory mediators Apr 9, 2021 Apr 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2316 Increased viral transcription and replication TLR Activation/Dysregulation Apr 9, 2021 Apr 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1592 Systemic cholesterol increased Foam cell formation Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2698 Increased S1-P Histone deacetylase inhibition Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2329 Increased Sodium-sensitive hypertension Chronic kidney disease Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2291 SARS-CoV-2 production Oxidative Stress Mar 25, 2021 Mar 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2351 SARS-CoV-2 production TLR Activation/Dysregulation Apr 16, 2021 Apr 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2358 SARS-CoV-2 production Diminished Protective Response to ROS Apr 20, 2021 Sep 26, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2488 SARS-CoV-2 production Increase, Cell death Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2498 SARS-CoV-2 production Viral infection, proliferated Oct 24, 2021 Mar 31, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2545 SARS-CoV-2 production Sustentacular cells, decrease Jan 5, 2022 Jan 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2546 SARS-CoV-2 production Disruption of the intestinal barrier Jan 5, 2022 Jun 14, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1770 Respiratory irritability Increased Airway Hyper-responsiveness,Cough, Dyspnea Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1788 Increased reactive oxygen species (in the mitochondria) Mitochondrial Injury Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1957 Increased reactive oxygen species (in the mitochondria) Mitochondrial dysfunction Jun 15, 2019 Jun 15, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1719 Increased pro-inflammatory mediators Cell injury/death Feb 1, 2018 Feb 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1764 Increased pro-inflammatory mediators Activation, Stellate cells Aug 2, 2018 Aug 2, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1777 Increased pro-inflammatory mediators Leukocyte recruitment/activation Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1902 Increased pro-inflammatory mediators N/A, Breast Cancer May 7, 2019 May 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1903 Increased pro-inflammatory mediators Increase in RONS May 7, 2019 May 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1908 Increased pro-inflammatory mediators Increase, Cell Proliferation (Epithelial Cells) May 10, 2019 May 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2777 Increased pro-inflammatory mediators Increase, Endothelial Dysfunction Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2902 Increased cytokine expression Increase in inflammation May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1954 plasma homocysteine increases brain Homocysteine level increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1193 increased or inappropriate, mantel display Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1219 increased or inappropriate, mantel display Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1220 increased or inappropriate, mantel display induced, parturition Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1584 Increased NKA Increased Airway Hyper-responsiveness,Cough, Dyspnea Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1585 Increased NKA Leukocyte infiltration Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1773 Increased NKA Respiratory irritability Sep 24, 2018 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2430 MyD88 activation Increased activation, Nuclear factor kappa B (NF-kB) Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                200 Increased Mortality Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  428 Increased Mortality Decreased, Population trajectory Nov 29, 2016 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    756 Increased Mortality Decreased, population 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1191 Increased Mortality Decreased, Population size Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2013 Increased Mortality Decrease, Population growth rate Dec 20, 2019 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2486 Increased Mortality Decline, Population trajectory Oct 8, 2021 Oct 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2816 Modified Proteins Cataracts Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2610 Increase,miRNA levels Decrease,SIRT1(sirtuin 1) levels Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1322 increased mantel display Induced parturition Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2900 increased lipid accumulation Increased fat mass May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2939 Increased LCN2/iron complex Increased intracelluar Iron Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2940 Increased intracelluar Iron Neuronal dysfunction Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2951 Increased intracelluar Iron Oxidative Stress in Brain Jun 21, 2023 Jun 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2029 Increased monitor peptide Increased blood CCK level Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2062 Increased inflammatory immune responses Increase, the risk of acute respiratory failure Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2513 Increased inflammatory immune responses Heart attack Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1953 Homocysteine increases plasma homocysteine increases Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1959 Homocysteine increases Plasma HCY level Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2876 Increased fat mass Recruitment of inflammatory cells Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2901 Increased fat mass Increased cytokine expression May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2031 Increased acinar cell exocrine secretion Acinar cell proliferation Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            51 Increased Cholinergic Signaling Decrease, Population growth rate Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              434 Increased Cholinergic Signaling Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                457 Increased Cholinergic Signaling Respiratory distress/arrest Nov 29, 2016 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2005 Increased Cholinergic Signaling Cardiovascular dysregulation Nov 25, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2011 Increased Cholinergic Signaling Impaired coordination and movement Dec 20, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2410 Increased Cholinergic Signaling Neuronal network function, Decreased Jun 24, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2412 Increased Cholinergic Signaling Cognitive Function, Decreased Jun 24, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1579 Increased CGRP Increased Airway Hyper-responsiveness,Cough, Dyspnea Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1580 Increased CGRP Increase, hypertension Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1586 Increased CGRP Leukocyte infiltration Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1587 Increased CGRP Respiratory irritability Jun 27, 2017 Jun 27, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1955 brain Homocysteine level increases Neuronal dysfunctions induction Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2030 Increased blood CCK level Increased acinar cell exocrine secretion Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1647 Decreased Leydig Cells Reduction, Testosterone synthesis in Leydig cells Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2066 Increased AngII Increase plasma Ang II Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2298 Increased AngII Impaired gustatory nerve Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2300 Increased AngII Increased proinflammatory mediators Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2317 Increased AngII Sodium inhibition, Sweet enhancement Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2327 Increased AngII Increased Ang II type 1 receptor (AT1R) Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2593 Increased AngII Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) Mar 3, 2022 Mar 3, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2323 Increased Ang II type 1 receptor (AT1R) Increased, Reactive oxygen species Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1612 increased adipogenesis obesity Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2899 Increased adipocyte size Increased fat mass May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2898 Increased adipocyte numbers Increased fat mass May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1080 Increased activity, beta-2 adrenergic receptor relaxation, smooth muscle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1238 Increased activation, Nuclear factor kappa B (NF-kB) Increase, Phenotypic enzyme activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2309 Increased activation, Nuclear factor kappa B (NF-kB) Increased proinflammatory mediators Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2431 Increased activation, Nuclear factor kappa B (NF-kB) Release, Cytokine Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2432 Increased activation, Nuclear factor kappa B (NF-kB) Increased pro-inflammatory mediators Jul 8, 2021 Jul 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2612 Increased activation, Nuclear factor kappa B (NF-kB) Antagonism, Estrogen receptor Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2509 Upregulation of ACE2 SARS-CoV-2 cell entry Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2527 increased atRA concentration premature meiosis, male germ cells Nov 10, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2068 Increase,collagen synthesis Induction lung fibrosis Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    336 Increase, Vitellogenin synthesis in liver Increase, Plasma vitellogenin concentrations Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2738 Increase, Vitellogenin mRNA Delay, Ovarian maturation Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1444 Increase, vascular smooth muscle contraction Increase, hypertension Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3018 Increase, Vascular disrupting effects Angiogenesis disfunction Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      795 Increase, Urinary bladder calculi Increase, Cytotoxicity (urothelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1663 Increase, Uncoupling of photophosphorylation Decrease, ATP production Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2528 Increase, TNF Decrease, GLUT4 Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2178 Increase, Tissue/organ damage Decrease, Growth Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        888 Increase, Tissue Degeneration, Necrosis & Atrophy Increase, Respiratory or Squamous Metaplasia Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        741 Increase, Thyroid-stimulating hormone (TSH) Increase, Hypertrophy and proliferation (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2064 Increase, the risk of acute respiratory failure Decreased mortality Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2135 Increase, the risk of acute respiratory failure Increased Mortality May 13, 2020 May 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1489 Increase, surfactant Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1745 Increase, SUR binding Increase, Cell membrane depolarization May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2684 Increase, slincR expression Decrease, sox9 expression Jun 30, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2690 Increase, slincR expression Smaller and morphologically distorted facial cartilage structures Jun 30, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2727 Increase, slincR expression Altered, Cardiovascular development/function Aug 2, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2742 Increase, sex ratio (F/M) Increase, developmental abnormalities Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1460 Increase, seizure Increased, epilepsy Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1930 Increase, SAM depletion Increase, DNA hypomethylation May 30, 2019 May 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              889 Increase, Respiratory or Squamous Metaplasia Increase, Cell Proliferation Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              280 Increase, Renal pathology due to VTG deposition Altered, Larval development Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              797 Increase, Regenerative cell proliferation (urothelial cells) Increase, Hyperplasia (urothelial) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              760 Increase, Regenerative cell proliferation (tubular epithelial cells) Increase, Hyperplasia (renal tubular cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              785 Increase, Regenerative cell proliferation (tubular epithelial cells) Increase, Hyperplasia (tubular epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              727 Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells) Increase, Hyperplasia (terminal bronchiolar cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              789 Increase, Regenerative cell proliferation (hepatocytes) Increase, Preneoplastic foci (hepatocytes) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              782 Increase, Regenerative cell proliferation (forestomach epithelial cells) Increase, Hyperplasia (forestomach epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              779 Increase, Regenerative cell proliferation (corneal cells) Increase, Papillomas/carcinomas (squamous cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              282 Increase, ROS production Decreased, Nitric Oxide Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              283 Increase, ROS production Increased, Oxidative damage Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              912 Increase, ROS production Mitochondrial dysfunction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1602 Increase, ROS production Increase, DNA Damage Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1603 Increase, ROS production Increased, LPO Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1623 Increase, ROS production Increased, secretion of local growth factors Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1754 Increase, ROS production Decrease, Coupling of OXPHOS Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2089 Increase, ROS production Increase, Protein oxidation Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2093 Increase, ROS production Decrease, MMP Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2099 Increase, ROS production Increase,Oxidative DNA damage Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2187 Increase, ROS production Increase, Apoptosis Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2225 Increase, ROS production Increase, Global methylation Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2305 Increase, ROS production Inhibition, Nuclear factor kappa B (NF-kB) Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2308 Increase, ROS production Increased activation, Nuclear factor kappa B (NF-kB) Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2348 Increase, ROS production D1 protein deactivation Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2590 Increase, ROS production Increase, Oxidative DNA damage Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2998 Increase, ROS production Increase, Oxidative Stress Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1466 Increase, ROS Peptide Oxidation Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1595 Increase, ROS Increase, DNA Damage Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1598 Increase, ROS Increased, LPO Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1876 Increase, ROS Increase,Oxidative DNA damage Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2342 Increase, ROS D1 protein deactivation Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2345 Increase, ROS Decrease, MMP Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2826 Increase, ROS Oxidative Stress Jan 9, 2023 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        272 Increase, RBC congestion in liver N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2802 behavioral change leading to possible reduced feeding opportunity Decrease, Growth Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2090 Increase, Protein oxidation Increase, Abnormal osmoregulation Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2223 Increase, Protein oxidation Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          944 Increased goblet cell proliferation Goblet cell hyperplasia Nov 29, 2016 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2339 Increase, Programmed cell death Decrease, Leaf development Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2553 Increase, Programmed cell death Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2835 Increase, Pro-Inflammatory Mediators Abnormal Neural Remodeling Jan 25, 2023 Feb 16, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2839 Increase, Pro-Inflammatory Mediators Impairment, Learning and memory Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              774 Increase, Preneoplastic foci (hepatocytes) Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1744 Increase, Premature molting Increase, Mortality May 24, 2018 Feb 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2634 Increase, predation Decrease, Population growth rate Apr 6, 2022 Apr 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2555 Increase, Pollen abnormal Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1474 Increase, platelet aggregation Inhibit, gastric ulcer formation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              254 Increase, Plasma vitellogenin concentrations Increase, Renal pathology due to VTG deposition Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2409 increase, placental insufficiency increase, Preeclampsia May 31, 2021 May 31, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1230 Increase, Phenotypic enzyme activity Increase, cell proliferation (hepatocytes) Nov 29, 2016 Dec 31, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1231 Increase, Phenotypic enzyme activity Increase, Clonal Expansion of Altered Hepatic Foci Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1241 Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2340 Increase, OEC damage Decrease, Photosystem II efficiency Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2220 Increase, Oxygen consumption Increase, ROS production Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1362 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Increased, DNA Damage-Repair Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1364 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Activation, HIF-1 Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3166 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Mitochondrial dysfunction Mar 14, 2024 Mar 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2897 Increase, Oxidative Stress TH synthesis, Decreased Apr 24, 2023 May 23, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2980 Increase, Oxidative Stress Activation, inflammation pathway Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2993 Increase, Oxidative Stress Abnormal expression of NO Aug 20, 2023 Aug 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2999 Increase, Oxidative Stress Activated ANG/Tie2 pathway Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3000 Increase, Oxidative Stress Activation, Dll4-Notch pathway Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3001 Increase, Oxidative Stress Activated BMP/TGF-beta pathway Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3002 Increase, Oxidative Stress Activated Wnt/Frizzled pathway Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3003 Increase, Oxidative Stress Uncoupling, eNOS Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3004 Increase, Oxidative Stress Activated AKT/ERK/PI3K pathway Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3005 Increase, Oxidative Stress Inhibition VEGF/VEGFR pathway Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3033 Increase, Oxidative Stress Increase, Apoptosis Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3130 Increase, Oxidative Stress Mitochondrial dysfunction Feb 21, 2024 Feb 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    763 Increase, Oxidative metabolism Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1877 Increase,Oxidative DNA damage Increase, Apoptosis Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2190 Increase,Oxidative DNA damage Apoptosis Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2221 Increase,Oxidative DNA damage Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2558 Increase,Oxidative DNA damage Increase, Oocyte apoptosis Feb 4, 2022 Feb 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2559 Increase,Oxidative DNA damage Increase, Ovarian somatic cell apoptosis Feb 4, 2022 Feb 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3095 Increase,Oxidative DNA damage Increase, DSB Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1909 Increase, Oxidative DNA damage Inadequate DNA repair May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1913 Increase, Oxidative DNA damage Increase, DNA strand breaks May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1914 Increase, Oxidative DNA damage Increase, Mutations May 19, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2591 Increase, Oxidative DNA damage Increase, Follicular atresia Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2592 Increase, Oxidative DNA damage Increase, Oocyte apoptosis Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2117 Increase, Ovarian somatic cell apoptosis (F3) Increase, Ovarian follicle breakdown (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2106 Increase, Ovarian somatic cell apoptosis Increase, Ovarian follicle breakdown Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2118 Increase, Ovarian follicle breakdown (F3) Decrease, Oogenesis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2107 Increase, Ovarian follicle breakdown Decrease, Oogenesis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2560 Increase, Ovarian follicle breakdown Decrease, Fecundity Feb 4, 2022 Feb 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1747 Increase, Opening of voltage-dependent calcium channel Decrease, Cuticular chitin content May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2113 Increase, Oocyte apoptosis (F3) Decrease, Oogenesis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2104 Increase, Oocyte apoptosis Decrease, Oogenesis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2386 Increase, Oocyte apoptosis impaired, Fertility May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2400 Increase, Oocyte apoptosis Decrease of egg production and cummulative fecundity May 18, 2021 May 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1344 Increase, E75b expression Increase, Ftz-f1 expression Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              726 Increase, Necrosis (terminal bronchiolar cells) Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1874 Increase, Necrosis Increase, Mortality Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2122 Increase, Necrosis Increase, Ovarian follicle breakdown May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2177 Increase, Necrosis Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2465 Increase, Necrosis Increased, Kidney Failure Aug 11, 2021 Aug 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1443 Increase, myosin light chain phosphorylation Increase, vascular smooth muscle contraction Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    894 Increase, Mutations in Critical Genes Increase, Site of Contact Nasal Tumors Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    202 Increase, Mutations Increase, Heritable mutations in offspring Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    899 Increase, Mutations Increase, Cancer Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alkylation of DNA leading to cancer 2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alkylation of DNA leading to cancer 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1896 Increase, Mutations Increase, Cell Proliferation (Epithelial Cells) May 7, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1978 Increase, Mutations Increase, Cell Proliferation Aug 29, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1984 Increase, Mutations Increase, lung cancer Aug 29, 2019 Jan 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2609 Increase, Mutations Increase,miRNA levels Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1485 Increase, mucous Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1486 Increase, mucosal blood flow Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    991 Increase, Mucin production Hypersecretion, Mucus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1315 Increase, Mucin production Chronic, Mucus hypersecretion Nov 29, 2016 Aug 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2859 Increase, Mucin production Decreased lung function Mar 15, 2023 Mar 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        198 Increase, Mortality Decrease, Fecundity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          199 Increase, Mortality Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1004 Increase, Mortality Decreased, population 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1013 Increase, Mortality Decreased, Population size Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2463 Increase, Mortality Decrease, Population growth rate Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2797 Increase, Mitochondrial swelling Cell injury/death Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2183 Increase, Complex III dysfunction Increase, Cyt c release Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2186 Increase, Complex III dysfunction Increase, ROS production Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1781 Increase, Mitochondrial complex III antagonism Decrease in mitochondrial oxidative phosphorylation Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1784 Increase, Mitochondrial complex III antagonism Increased reactive oxygen species (in the mitochondria) Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1872 Increase, Mitochondrial complex III antagonism Decrease, OXPHOS Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1875 Increase, Mitochondrial complex III antagonism Increase, ROS Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2230 Increase, Mitochondrial complex III antagonism Decrease, ATP pool Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2189 Increase, Complex I dysfunction Increase, ROS production Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2119 Increase, Mitochondrial ATP synthase antagonism Decrease, OXPHOS May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2229 Increase, Mitochondrial ATP synthase antagonism Decrease, ATP pool Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                461 Increase, Luteinizing hormone (LH) Increase proliferation, Leydig cell Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                169 Increase, Liver and splenic hemosiderosis N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1477 Increase, leukocyte adherence Activate, leukocyte Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1441 Increase, intracellular calcium Activate, calmodulin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2954 Increase, intracellular calcium Disruption, neurotransmitter release Jun 27, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2968 Increase, intracellular calcium Apoptosis Jul 18, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3140 Increase, intracellular calcium Mitochondrial dysfunction Mar 6, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1390 Increase, insulin Activation, insulin receptor Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1440 Increase, inositol triphosphate Increase, intracellular calcium Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  778 Increase, Inflammation (corneal cells) Increase, Regenerative cell proliferation (corneal cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  781 Increase, Inflammation Increase, Regenerative cell proliferation (forestomach epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  929 Increase, Inflammation Cholestasis, Pathology Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1722 Increase, Inflammation Expression of Collagen Mar 18, 2018 Mar 18, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1724 Increase, Inflammation EMT Mar 18, 2018 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1839 Increase, Inflammation Fibroproliferative airway lesions Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2573 Increase, Inflammation Increased, Invasion Feb 15, 2022 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2574 Increase, Inflammation Increase, angiogenesis Feb 15, 2022 Dec 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2976 Increase, Inflammation General Apoptosis Jul 31, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1002 Increase, Incomplete ecdysis Increase, Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1190 Increase, Incomplete ecdysis Increased Mortality Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2750 Increase, Incomplete ecdysis Increase, delay in oviposition Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2751 Increase, Incomplete ecdysis Decrease, hatching of egg Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2759 Increase, Incomplete ecdysis Increase, developmental abnormalities Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2018 Increase of IL-23 Th17 cell migration and inflammation induction Dec 27, 2019 Dec 27, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      742 Increase, Hypertrophy and proliferation (follicular cell) Increase, Hyperplasia (follicular cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1581 Increase, hypertension Respiratory irritability Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        798 Increase, Hyperplasia (urothelial) Increase, Adenomas/carcinomas (urothelial) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2085 Increase, Hyperplasia (urothelial) carcinogenicity Apr 21, 2020 Apr 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        786 Increase, Hyperplasia (tubular epithelial cells) Increase, Adenomas/carcinomas (renal tubular) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        728 Increase, Hyperplasia (terminal bronchiolar cells) Increase, Adenomas/carcinomas (bronchioloalveolar) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        761 Increase, Hyperplasia (renal tubular cells) Increase, Adenomas/carcinomas (renal tubular) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        731 Increase, Hyperplasia (Leydig cells) Increase, Leydig cell tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        771 Increase, Hyperplasia (glandular epithelial cells of endometrium) Increase, Endometrial adenocarcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2972 Increase, Hyperplasia (glandular epithelial cells of endometrium) Genomic instability Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        783 Increase, Hyperplasia (forestomach epithelial cells) Increase, Papillomas/carcinomas (squamous cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        743 Increase, Hyperplasia (follicular cells) Increase, Adenomas/carcinomas (follicular cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1994 Increase, hypermethylation of the promotor region of GnRHR Decease, expression of GnRHR Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2920 Increase, Gonadotropins concentration in plasma Derease, testosterone levels May 22, 2023 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3212 Increase, Gonadotropins concentration in plasma Decrease, testosterone levels May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2858 Increase, goblet cell number Increase, Mucin production Mar 15, 2023 Mar 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2794 Increase, Glycolysis Decrease, Glucose pool Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2885 Increase, Glucuronidation of T4 Increased, Clearance of thyroxine from serum Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2226 Increase, Global methylation Increase, Apoptosis Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1234 Increase, Genes involved in fatty acid oxidation Peptide Oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1240 Increase, Genes involved in fatty acid oxidation Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1885 Increase, Gene expression Decrease, Fecundity Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1462 Increase, GABA Activate, GABA-A receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1345 Increase, Ftz-f1 expression Decrease, Circulating ETH Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3097 Increase, Formation of DNA photoproducts Increase, DSB Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1597 Increase, Follicular atresia Decrease, Oogenesis Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2211 Increase, Follicular atresia Decrease, Fecundity Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1417 Increase, Fatty acid β-oxidation Decrease, cytosolic fatty acid Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      132 Increase, FA Influx Accumulation, Triglyceride Nov 29, 2016 Mar 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2330 Excitation of intracellular water Increase in RONS Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        567 Increase, Energetic demands and therefore metabolic stress Increased, Appetite and hunger Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2778 Increase, Endothelial Dysfunction Vascular remodeling Sep 28, 2022 Sep 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2784 Increase, Endothelial Dysfunction Occurrence, Vascular Remodeling Oct 17, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          116 Increase, EcR agonism Induction, Chitin degradation and resorption Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            998 Increase, EcR agonism Decrease, Circulating ETH Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              999 Increase, EcR agonism Decreased, synthesis and secretion of molting fluid proteases Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1007 Increase, EcR agonism Decreased, Synthesis of molting fluid proteases Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1343 Increase, EcR agonism Increase, E75b expression Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  732 Increase, Dopaminergic activity Decreased, Prolactin Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  770 Increase, Dopaminergic activity Increase, Endometrial adenocarcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1911 Increase, DNA strand breaks Inadequate DNA repair May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1931 Increase, DNA strand breaks Increase, Mutations Jun 2, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1939 Increase, DNA strand breaks Increase, Chromosomal aberrations Jun 3, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2074 Increase, DNA strand breaks Increase, Apoptosis Apr 6, 2020 Apr 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2587 Increase, DNA strand breaks Increase, Follicular atresia Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2589 Increase, DNA strand breaks Increase, Oocyte apoptosis Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2841 Increase, DNA strand breaks Abnormal Neural Remodeling Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2856 Increase, DNA strand breaks Altered Signaling Mar 10, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1883 Increase, DNMT inhibition Increase, DNA hypomethylation Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2101 Increase, DNMT inhibition Decrease, Global DNA methylation Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3098 Increase, DNMT inhibition Increase, DSB Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1993 Increase, DNMT expression Increase, hypermethylation of the promotor region of GnRHR Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1884 Increase, DNA hypomethylation Increase, Gene expression Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1887 Increase, DNA hypomethylation Decrease, Transgenerational DNA methylation Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1635 Increase, DSB MLL translocation Aug 2, 2017 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3096 Increase, DSB Increase, Apoptosis Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3099 Increase, DSB Increase, Casp transcription Nov 16, 2023 Nov 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1301 Increase, DNA Damage Altered, Gene Expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1468 Increase, DNA Damage Increase, Apoptosis Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1897 Increase, DNA Damage Increase, Mutations May 7, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1898 Increase, DNA Damage Tissue resident cell activation May 7, 2019 May 10, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1899 Increase, DNA Damage Increase mutations May 7, 2019 May 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2338 Increase, DNA Damage Increase, Programmed cell death Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2381 Increase, DNA Damage Altered, Meiotic chromosome dynamics May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2382 Increase, DNA Damage Increase, Oocyte apoptosis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2595 Increase, DNA Damage Activation of TP53 Mar 9, 2022 Mar 9, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2622 Increase, DNA Damage Decreased spermatogenesis Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2790 Increase, DNA Damage Cell cycle, disrupted Oct 25, 2022 Oct 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1626 Differentiation of fibroblasts Expression of Collagen Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1654 Differentiation of fibroblasts Accumulation, Collagen Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2743 Increase, developmental abnormalities Increase, Mortality Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2746 Increase, Defects in tanning of new cuticle Increase, impairment of cuticle sclerotization Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2747 Increase, Defects in tanning of new cuticle Increase, pigmentation Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2332 D1 protein deactivation Decrease, Photosystem II efficiency Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1736 Increase, D1 protein antagonism Decrease, PSII activity May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  796 Increase, Cytotoxicity (urothelial cells) Increase, Regenerative cell proliferation (urothelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  784 Increase, Cytotoxicity (tubular epithelial cells) Increase, Regenerative cell proliferation (tubular epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  708 Increase, Cytotoxicity (renal tubular cell) Increase, Regenerative cell proliferation (tubular epithelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1676 Increase, Cytotoxicity (renal tubular cell) Occurrence, Kidney toxicity Oct 25, 2017 Mar 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Renal protein alkylation leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  788 Increase, Cytotoxicity (hepatocytes) Increase, Regenerative cell proliferation (hepatocytes) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  780 Increase, Cytotoxicity (epithelial cells) Increase, Inflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2659 Increase, Cytotoxicity (epithelial cells) Increased, Reactive oxygen species May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2664 Increase, Cytotoxicity (epithelial cells) Secondary genotoxicity May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  777 Increase, Cytotoxicity (corneal cells) Increase, Inflammation (corneal cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  767 Increase, Cytotoxicity (club cells) Increase, Necrosis (terminal bronchiolar cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  766 Increase, Cytotoxicity Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  887 Increase, Cytotoxicity Increase, Tissue Degeneration, Necrosis & Atrophy Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1693 Increase, cytosolic fatty acid steatohepatitis Nov 13, 2017 Nov 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1694 Increase, cytosolic fatty acid Increased, Liver Steatosis Nov 14, 2017 Nov 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2764 Increase, Cytosolic Ca Increase, Cell death Sep 13, 2022 Sep 13, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2766 Increase, Cytosolic Ca Cell injury/death Sep 27, 2022 Sep 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2184 Increase, Cyt c release Increase, Apoptosis Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3050 Increase, Cyt c release Caspase activation Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2078 Increase, Cripto-1 expression Inhibition, Activin signaling Apr 21, 2020 Jul 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2082 Increase, Cripto-1 expression Inhibition, Fin regeneration Apr 21, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1351 Increase, COX-2 expression Altered, Cardiovascular development/function Feb 9, 2017 Mar 28, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1450 Increase, cortisone Activation, Glucocorticoid Receptor Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3056 Increase, CNS Neural cell death Decrease, elavl3 Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3057 Increase, CNS Neural cell death Decrease, sox10 Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3058 Increase, CNS Neural cell death Decrease, mbp Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1232 Increase, Clonal Expansion of Altered Hepatic Foci Increase, hepatocellular adenomas and carcinomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        637 Increase, cilia movement Increased, locomotion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          639 Increase, cilia movement Increased, foot detachment Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1178 Increase, cilia movement premature, spawning 1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1187 Increase, cilia movement premature, Spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1217 Increase, cilia movement Increased, water pumping Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1218 Increase, cilia movement Depletion, energy reserves Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1321 Increase, cilia movement induced spawning Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1335 Increase, cilia movement Induced parturition Jan 30, 2017 Jan 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1979 Increase, Chromosomal aberrations Increase, Cell Proliferation Aug 29, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1985 Increase, Chromosomal aberrations Increase, lung cancer Aug 29, 2019 Jan 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    773 Increase, cell proliferation (hepatocytes) Increase, Preneoplastic foci (hepatocytes) Nov 29, 2016 Feb 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1239 Increase, cell proliferation (hepatocytes) Increase, Clonal Expansion of Altered Hepatic Foci Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2254 Increase, cell proliferation (hepatocytes) Increase, hepatocellular adenomas and carcinomas Dec 31, 2020 Dec 31, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1247 Increase, Cell Proliferation (Epithelial Cells) Increased, Ductal Hyperplasia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1907 Increase, Cell Proliferation (Epithelial Cells) Increase, Mutations May 8, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    890 Increase, Cell Proliferation Increased, Induced Mutations in Critical Genes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      893 Increase, Cell Proliferation Increase, Mutations in Critical Genes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      895 Increase, Cell Proliferation Increase, Site of Contact Nasal Tumors Nov 29, 2016 Dec 1, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1967 Increase, Cell Proliferation Lung cancer Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1980 Increase, Cell Proliferation Increase, lung cancer Aug 29, 2019 Jan 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2419 Increase, Cell Proliferation Increased, mesotheliomas Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2819 Increase, Cell Proliferation Cataracts Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1746 Increase, Cell membrane depolarization Increase, Opening of voltage-dependent calcium channel May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2708 Increase, Cell membrane depolarization Increased, Intracellular Calcium overload Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2788 Increase, Cell membrane depolarization Cell injury/death Oct 19, 2022 Oct 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3039 Increase, Cell membrane depolarization Opening VGCCs Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2215 Increase, Cell death Decrease, Growth Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2467 Increase, Cell death Altered, inner ear development Aug 23, 2021 Aug 29, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2489 Increase, Cell death Disruption of the intestinal barrier Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2706 Increase, Cell death Parkinsonian motor deficits Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2718 Increase, Cell death Neuroinflammation Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2760 Increase, Cell death Increased proinflammatory mediators Sep 1, 2022 Sep 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2842 Increase, Cell death Altered Bone Cell Homeostasis Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2863 Increase, Cell death Hippocampal Physiology, Altered Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2112 Increase, Casp transcription (F3) Increase, Oocyte apoptosis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2116 Increase, Casp transcription (F3) Increase, Ovarian somatic cell apoptosis (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2103 Increase, Casp transcription Increase, Oocyte apoptosis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2105 Increase, Casp transcription Increase, Ovarian somatic cell apoptosis Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3175 Increase, Cardiac remodelling Decrease LV function Apr 3, 2024 Apr 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                60 Increase, Ca++ (intracellular) Disruption, Mitochondrial electron transport chain Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2845 Bone Remodeling Bone Loss Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2741 Increase, Body volume of female adults Increase, developmental abnormalities Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2092 Increase, Body fluid overload Increase, Mortality Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2236 Increase, Biliary excretion TH glucuronide T4 in serum, Decreased Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1484 Increase, bicarbonate Activate, mucosal defense Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1469 Increase, Apoptosis Decrease, Oogenesis Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1596 Increase, Apoptosis Increase, Follicular atresia Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1741 Increase, Apoptosis Decrease, Growth May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1751 Increase, Apoptosis Increase, Mortality Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2075 Increase, Apoptosis Reduce, Sperm count Apr 6, 2020 Apr 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2185 Increase, Apoptosis Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2461 Increase, Apoptosis Increased, Kidney Failure Aug 5, 2021 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2602 Increase, Apoptosis Microcephaly Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2619 Increase, Apoptosis Decreased spermatogenesis Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2645 Increase, Apoptosis Occurrence, renal proximal tubular necrosis Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2725 Increase, Apoptosis Decrease, outgrowth Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2948 Increase, Apoptosis Inhibition of neurotransmitter release Jun 20, 2023 Jun 20, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3034 Increase, Apoptosis increased,Vascular endothelial dysfunction Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1473 Increase, angiogenesis Inhibit, gastric ulcer formation Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2578 Increase, angiogenesis N/A, Breast Cancer Feb 15, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3137 Increase, angiogenesis Metastasis, Breast Cancer Mar 5, 2024 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2910 Increase, Androgen receptor Alterations, Cellular proliferation / hyperplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1487 Increase, ammonium (NH4+) Decrease, surfactant Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2736 Increase, Alcohol dehydrogenase Increased, Estrogen receptor (ER) activity Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2091 Increase, Abnormal osmoregulation Increase, Body fluid overload Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2181 Increase, Abnormal osmoregulation Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2836 Abnormal Neural Remodeling Impairment, Learning and memory Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2749 Increase, pigmentation Increase, Incomplete ecdysis Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2748 Increase, impairment of cuticle sclerotization Increase, Incomplete ecdysis Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    398 Increase proliferation, Leydig cell Hyperplasia, Leydig cell Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2067 Increase plasma Ang II Increase,collagen synthesis Mar 17, 2020 Mar 17, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2138 Increase plasma Ang II Accumulation, Collagen May 15, 2020 May 15, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2435 Increase plasma Ang II Increased Ang II type 1 receptor (AT1R) Jul 13, 2021 Jul 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2799 methemocyanin formation (decrease overall oxygen binding capacity) Decrease overall oxygen binding capacity (methemocyanin formation) Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2800 methemocyanin formation (decrease overall oxygen binding capacity) Hemocyanin Bohr effect decrease Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2022 Increase of Th2 cells producing IL-4 Increase of autoantibody production Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2023 Increase of autoantibody production Exacerbation of SLE Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1795 Increase mutations Increase cell proliferation Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1800 Increase mutations Increase, lung cancer Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1900 Increase mutations Increase, Cell Proliferation (Epithelial Cells) May 7, 2019 May 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1904 Increase in RONS Increase, DNA Damage May 7, 2019 May 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1906 Increase in RONS Tissue resident cell activation May 7, 2019 May 9, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2331 Increase in RONS D1 protein deactivation Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2337 Increase in RONS Decrease, MMP Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2617 Increase in RONS Increased, Oxidative Stress Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2798 Increase in RONS methemocyanin formation (decrease overall oxygen binding capacity) Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2199 Increase in inflammation hepatitis Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2646 Increase in inflammation Occurrence, renal proximal tubular necrosis Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3177 Increase in inflammation Insulin resistance, increased Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1796 Increase chromosomal aberrations Increase cell proliferation Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1801 Increase chromosomal aberrations Increase, lung cancer Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2729 Increase chromosomal aberrations Increase,miRNA levels Aug 14, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1797 Increase cell proliferation Increase, lung cancer Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1793 DNA repair Increase mutations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1794 DNA repair Increase chromosomal aberrations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            164 Inadequate DNA repair Increase, Mutations Nov 29, 2016 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alkylation of DNA leading to cancer 2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alkylation of DNA leading to cancer 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Bulky DNA adducts leading to mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1910 Inadequate DNA repair Increase, DNA strand breaks May 19, 2019 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1912 Inadequate DNA repair Increase, Chromosomal aberrations May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2817 Inadequate DNA repair Cataracts Dec 18, 2022 Mar 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1353 Inactivation of PPARγ Activation of TGF-β signaling Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2156 Inactivation of PPARγ Activation, TGF-beta pathway Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1446 Inactivated, 5-HTR Reduce expression, BDNF Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1511 Inactivated, 5-HTR Reduced, BDNF May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            564 Impairment, Learning and memory Abnormal, Roll change within caste Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            583 Impairment, Learning and memory Abnormal, Foraging activity and behavior Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1644 Impairment, Learning and memory Decreased, locomotion Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2872 Impairment, Learning and memory decreased, IQ Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            125 Impairment, Endothelial network Insufficiency, Vascular Nov 29, 2016 Jan 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            976 Impairment, Endothelial network Altered, Cardiovascular development/function Nov 29, 2016 Jun 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3173 Impaired, urethral tube closure Hypospadias Mar 20, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            665 impaired, Thoracic shivering impaired, Hive thermoregulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2164 Impaired, Spermatogenesis Decrease, Fertility Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2274 Impaired, Spermatogenesis impaired, Fertility Jan 29, 2021 Aug 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2692 Impaired, Spermatogenesis Viable offspring, decreased Jul 18, 2022 Jul 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2937 Impaired, Spermatogenesis Decreased, Viable Offspring Jun 2, 2023 Sep 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  905 Impaired, Proteostasis Degeneration of dopaminergic neurons of the nigrostriatal pathway Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1943 Impaired, Proteostasis Cell injury/death Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2632 Impaired, Oocyte maturation and ovulation Increased, Oocyte Atresia Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3079 impaired, Learning and memory Parkinsonian motor deficits Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  563 impaired, Larval development Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  701 impaired, ion channels Altered, Action Potential Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  574 impaired, Hive thermoregulation Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1153 impaired, Hive thermoregulation Weakened, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2292 impaired, Fertility Decrease, Population growth rate Mar 26, 2021 Mar 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2387 impaired, Fertility Decrease of egg production and cummulative fecundity May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  572 impaired, Development Decrease, Number of worker bees Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1821 Impaired T cell activation Suppression, Suppression of T-cell dependent antibody response (TDAR) Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1822 Impaired T cell activation Impairment of TDAR Dec 25, 2018 Jun 1, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1922 Impaired T cell activation Impaired Ab production May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3029 Impaired Platelet Aggregation Increase, Vascular disrupting effects Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1976 Impaired oxygenation of the blood Acute inhalation toxicity Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1990 Impaired ovulation Decrease of egg production and cummulative fecundity Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2515 Altered mechanotransduction properties of pericytes Pericyte dysfunction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3179 Impaired insulin signaling Insulin resistance, increased Apr 9, 2024 Apr 9, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1938 Impaired inguinoscrotal phase Malformation, cryptorchidism Jun 3, 2019 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2000 Impaired IL-1R1 signaling Suppression of T cell activation Nov 17, 2019 Nov 17, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2002 Impaired IL-1R1 signaling Inhibition, Nuclear factor kappa B (NF-kB) Nov 17, 2019 Sep 29, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1815 Impaired IL-1 signaling Suppressed AP-1 Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1816 Impaired IL-1 signaling Suppressed NF-kB Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1825 Impaired IL-1 signaling Suppressed MyD88 Jan 6, 2019 Mar 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1920 Impaired IL-1 signaling Inhibition, Nuclear factor kappa B (NF-kB) May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2296 Impaired gustatory nerve taste impairment Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2012 Impaired coordination and movement Increased Mortality Dec 20, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2015 Impaired coordination and movement Decrease, Population growth rate Dec 20, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1835 Impaired axonial transport Sensory axonal peripheral neuropathy Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2506 Impaired axonial transport Dysfunctional synapses Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1820 Impaired antigen presentation Impaired T cell activation Dec 25, 2018 Dec 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1923 Impaired Ab production Impairment of TDAR May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1278 Leukocyte infiltration Respiratory irritability Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1290 Leukocyte infiltration Sensitization, Immune system Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3054 immune mechanisms antagonized IAV production increased Oct 3, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2196 Immune cell activation IFNγ signaling Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2318 Sodium inhibition, Sweet enhancement Impaired gustatory nerve Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2197 IFNγ signaling Increase in inflammation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3191 Hypomyelination Altered, white brain matter Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1083 Hypertrophy/hyperplasia, smooth muscle Promotion, mesovarian leiomyomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              755 hyperpolarisation, neuron N/A, Ataxia, paralysis, or hyperactivity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1566 hyperpolarisation, neuron Analgesia Jun 8, 2017 Jun 8, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1572 hyperpolarisation, neuron Anti-depressant Activity Jun 23, 2017 Jun 23, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1094 Hyperplasia, ovarian stromal cells Promotion, ovarian granular cell tumors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1093 Hyperplasia, ovarian epithelium Promotion, ovarian adenomas Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1115 Hyperplasia, Mammary gland Increased, latency period Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1116 Hyperplasia, Mammary gland Increased, Adenomas/carcinomas (mammary) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              462 Hyperplasia, Leydig cell impaired, Fertility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              158 Hyperplasia, Hyperplasia Promotion, Hepatocelluar carcinoma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2762 Hyperinflammation Increase, the risk of acute respiratory failure Sep 1, 2022 Sep 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2326 Hyperactivation of ACE/Ang-II/AT1R axis Increased AngII Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2521 Hyperactivation of ACE/Ang-II/AT1R axis Heart failure Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1709 Histone deacetylase inhibition Histone acetylation, increase Jan 21, 2018 Aug 5, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1714 Histone deacetylase inhibition p21 (CDKN1A) expression, increase Jan 21, 2018 Jul 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1715 Histone deacetylase inhibition Cell cycle, disrupted Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1716 Histone deacetylase inhibition Apoptosis Jan 21, 2018 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1717 Histone deacetylase inhibition Testicular atrophy Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1802 Histone deacetylase inhibition Reduced neural crest cell migration Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1805 Histone deacetylase inhibition Reduced collagen production Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2010 Histone deacetylase inhibition Spermatocyte depletion Dec 11, 2019 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2699 Histone deacetylase inhibition Neural tube defects Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1710 Histone acetylation, increase p21 (CDKN1A) expression, increase Jan 21, 2018 Jul 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1806 Histone acetylation, increase Altered, Gene Expression Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1997 Histone acetylation, increase Cell cycle, disrupted Nov 11, 2019 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3244 Histone acetylation, increase inhibition of E4 (Uracil-DNA Glycosylase) Jun 10, 2024 Jun 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3247 Histone acetylation, increase Recruitment of inflammatory cells Jun 10, 2024 Jun 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      748 Hippocampal Physiology, Altered Cognitive Function, Decreased Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2484 Hippocampal Physiology, Altered Loss, Cochlear function Sep 14, 2021 Sep 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2864 Hippocampal Physiology, Altered Impairment, Learning and memory Apr 3, 2023 Apr 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      747 Hippocampal gene expression, Altered Hippocampal anatomy, Altered Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2886 Hippocampal gene expression, Altered Hippocampal Physiology, Altered Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      749 Hippocampal anatomy, Altered Hippocampal Physiology, Altered Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2850 hERG channel blockade Inhibition of rapid delayed rectifying potassium current Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2535 hERG channel biogenesis interference Direct hERG channel blockage Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2536 hERG channel biogenesis interference Induction of hERG trafficking defects Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1514 Hepatocytotoxicity Sustained proliferation May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1517 Hepatocytotoxicity Liver Cancer May 30, 2017 May 1, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1166 Hemostasis, Depletion from blood of fully functional carboxylated clotting factors Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1546 Helicobacter pylori infection Increase, ammonium (NH4+) Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2508 Heart failure Upregulation of ACE2 Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2514 Heart failure Altered mechanotransduction properties of pericytes Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2825 Heart failure Increase, Mortality Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2533 Gut dysbiosis Disruption of the intestinal barrier Dec 2, 2021 Dec 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2544 Gut dysbiosis Recruitment of inflammatory cells Dec 15, 2021 Dec 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1926 GSK3beta inactivation β-catenin activation May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2485 GSK3beta inactivation Repression of Gbx2 expression Oct 3, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3142 Reduced granulosa cell proliferation irregularities, ovarian cycle Mar 7, 2024 Mar 7, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1374 Glutathione synthesis Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1378 Glutathione homeostasis Hepatotoxicity Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1686 Glutamate dyshomeostasis Cell injury/death Nov 9, 2017 Feb 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1691 Glutamate dyshomeostasis Neuronal network function, Decreased Nov 9, 2017 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1645 GR Agonist, Activation Decreased Leydig Cells Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1646 GR Agonist, Activation Repressed expression of steroidogenic enzymes Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2418 Genomic instability Increase, Cell Proliferation Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2973 Genomic instability endometrioid adenocarcinoma Type I Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        684 Generation, Amplified excitatory postsynaptic potential (EPSP) Occurrence, A paroxysmal depolarizing shift Nov 29, 2016 May 15, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1289 Generation of novel epitopes , Antigen presentation Sensitization, Immune system Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1733 General Apoptosis Neurodegeneration Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2977 General Apoptosis Increase, Cancer Jul 31, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1962 Frustrated phagocytosis Release, Cytokine Jul 3, 2019 Aug 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2415 Frustrated phagocytosis Increased proinflammatory mediators Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2416 Frustrated phagocytosis Increased, Reactive oxygen species Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1925 Frizzled activation GSK3beta inactivation May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2447 FOXJ1 Protein, Decreased Motile Cilia Number/Length, Decreased Jul 23, 2021 Aug 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2437 foxi1 expression, increased six1b expression, increased Jul 14, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1062 Formation, The binding of FK506 with FKBP12 Inhibition, Calcineurin Activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              344 Formation, Pro-mutagenic DNA Adducts Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                345 Formation, Pro-mutagenic DNA Adducts Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                352 Formation, Pro-mutagenic DNA Adducts Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  548 Formation, Pro-mutagenic DNA Adducts Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  551 Formation, Pro-mutagenic DNA Adducts Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  860 Formation, Mallory body Formation, Liver fibrosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1854 Protein photo-adducts Inflammatory events Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1591 HDL-SAA formation Systemic cholesterol increased Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1593 HDL-SAA formation Foam cell formation Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1853 DNA photo-adducts Inflammatory events Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1594 Foam cell formation Atherosclerosis Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1841 Fibroproliferative airway lesions Bronchiolitis obliterans Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2678 Fibroblast proliferation and differentiation Airway remodeling Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2352 Hypofibrinolysis Bradykinin, activated Apr 20, 2021 Apr 20, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2356 Hypofibrinolysis Increased proinflammatory mediators Apr 20, 2021 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            266 Feminisation or incomplete development, Primary and accessory male sex organs N/A, Impairment of reproductive capacity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1749 Fatty Acid Beta Oxidation, Decreased Decreased, Ketogenesis (production of ketone bodies) Jun 11, 2018 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1169 Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1165 Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo Hemostasis, Depletion from blood of fully functional carboxylated clotting factors Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2686 Smaller and morphologically distorted facial cartilage structures Increase, Early Life Stage Mortality Jun 30, 2022 Apr 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2439 eya1 expression, inhibited Increase, Cell death Jul 14, 2021 Aug 22, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2971 Expression of factors ruling proliferation, modified Increase, Hyperplasia (glandular epithelial cells of endometrium) Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1357 Expression of Collagen Collagen Deposition Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1273 Sensory Airway Irritation Cough, Dyspnea, Sneezing, Acute respiratory effect Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2880 ERa inactivation Increased adipocyte size Apr 6, 2023 Apr 6, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2881 ERa inactivation Increased adipocyte numbers Apr 6, 2023 Apr 6, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2906 ERa inactivation increased lipid accumulation May 4, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2929 ERa inactivation Decreased, Mitochondrial fatty acid beta-oxidation May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2930 ERa inactivation Increased, Reactive oxygen species May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1627 EMT Expression of Collagen Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1655 EMT Accumulation, Collagen Aug 16, 2017 Aug 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1725 EMT Lung fibrosis Mar 18, 2018 Mar 18, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1779 EMT Collagen Deposition Nov 20, 2018 Nov 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1840 EMT Fibroproliferative airway lesions Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2154 EMT Pulmonary fibrosis Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2614 EMT Metastasis, Breast Cancer Mar 22, 2022 Sep 26, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3200 EMT Resistant gastric cancer Apr 23, 2024 Apr 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3204 EMT Airway remodeling May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2970 Epigenetic modification process Expression of factors ruling proliferation, modified Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3170 Epididymal agenesis Impaired, Spermatogenesis Mar 20, 2024 Apr 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2453 Endothelial cell dysfunction Release, Cytokine Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2511 Endothelial cell dysfunction dysfunction of microcirculation Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2711 Endoplasmic reticulum stress Unfolded Protein Response Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1775 Endocytosis Disruption, Lysosome Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2680 Emphysema Chronic obstructive pulmonary disease Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1856 Eczematous eruption Scaling, Lichenification Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2493 ACE2 dysregulation Recruitment of inflammatory cells Oct 19, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2532 ACE2 dysregulation Gut dysbiosis Dec 2, 2021 Dec 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2831 ACE2 dysregulation (Micro)vascular dysfunction Jan 23, 2023 Feb 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3223 Dysregulation of transcriptional expression within PPAR signaling network Decreased, Mitochondrial fatty acid beta-oxidation May 14, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3224 Dysregulation of transcriptional expression within PPAR signaling network Disrupted Lipid Storage May 14, 2024 May 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2006 Cardiovascular dysregulation Respiratory distress/arrest Nov 25, 2019 Dec 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2502 Dysfunctional autophagy Accumulation, Toxic Tau oligomers Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2676 Dysfunctional autophagy Emphysema Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2136 Downregulation of ACE2 Increase plasma Ang II May 15, 2020 May 15, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2137 Downregulation of ACE2 Increased AngII May 15, 2020 May 15, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2517 Downregulation of ACE2 Ang (1-7) levels reduced Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              446 Down Regulation, K-Cl co-transporter 2 (KCC2) Delay, Developmental GABA shift Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                524 Down Regulation, HMGCS2 Decreased, Ketogenesis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1373 Down Regulation, GSS and GSTs gene Glutathione synthesis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1376 Down Regulation, GSS and GSTs gene Glutathione homeostasis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                520 Down Regulation, CPT1A Decreased, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1497 Dopamine release in the brain, decreased Locomotor activity, decreased May 2, 2017 May 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1502 Dopamine release in the brain, decreased Sexual behavior, decreased May 9, 2017 May 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                843 Disturbance, Lysosomal function Occurrence, Cytoplasmic vacuolization (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                844 Disturbance, Lysosomal function Occurrence, Ballooning degeneration (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                845 Disturbance, Lysosomal function Occurrence, Cytoplasmic vacuolization (Bile duct cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                846 Disturbance, Lysosomal function Occurrence, Cytoplasmic vacuolization (kupffer cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1678 Disturbance, Lysosomal function Disruption, Lysosome Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1834 Disturbance in microtubule dynamic instability Impaired axonial transport Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1842 Distribution of chemicals Absorption of photon energy Feb 4, 2019 Feb 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1762 Disruption, Sarcomere assembly Decrease, Cardiac contractility Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2562 Disruption, Progenitor cells of second heart field Reduced neural crest cell migration Feb 8, 2022 Feb 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2955 Disruption, neurotransmitter release Impairment, Learning and memory Jun 27, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3080 Disruption, neurotransmitter release impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  188 Disruption, Mitochondrial electron transport chain Decrease, Mitochondrial ATP production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  189 Disruption, Mitochondrial electron transport chain Increase, ROS production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  715 Disruption, Microtubule dynamics Disorganization, Meiotic Spindle Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  911 Disruption, Lysosome Increase, ROS production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    921 Disruption, Lysosome Peptide Oxidation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      993 Disruption, Lysosome Mitochondrial dysfunction Nov 29, 2016 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1679 Disruption, Lysosome Increase, Cytotoxicity (renal tubular cell) Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1761 Disruption, Intracellular calcium mobilization Disruption, Sarcomere assembly Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2615 Altered kinetics of sodium channel Altered, Action Potential Mar 25, 2022 Mar 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2625 Altered kinetics of sodium channel Disruption in action potential generation Mar 31, 2022 Mar 31, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3221 Disrupted PPAR isoform nuclear signaling Dysregulation of transcriptional expression within PPAR signaling network May 14, 2024 May 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3222 Disrupted PPAR isoform nuclear signaling Decreased, Mitochondrial fatty acid beta-oxidation May 14, 2024 May 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2481 Oocyte meiosis, disrupted Ovarian follicle pool, reduced Sep 13, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3210 Disrupted Lipid Storage Accumulation, Fatty acid May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3211 Disrupted Lipid Storage Accumulation, Triglyceride May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2246 Displacement, Serum thyroxine (T4) from transthyretin Increased, Free serum thyroxine (T4) Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2249 Displacement, Serum thyroxine (T4) from carrier protein Increased, Free serum thyroxine (T4) Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          737 Disorganization, Meiotic Spindle Altered, Meiotic chromosome dynamics Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3145 Direct mitochondrial inhibition Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2537 Direct hERG channel blockage Inhibition of Ikr Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2359 Diminished Protective Response to ROS Coagulation Apr 20, 2021 Jan 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2413 Diminished Protective Response to ROS inflammasome activity, increased Jun 25, 2021 Jun 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            973 dimerization, AHR/ARNT reduced dimerization, ARNT/HIF1-alpha Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1350 dimerization, AHR/ARNT Increase, COX-2 expression Feb 9, 2017 May 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1996 dimerization, AHR/ARNT Increase, DNMT expression Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2682 dimerization, AHR/ARNT Decrease, sox9 expression Jun 30, 2022 Jun 30, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2683 dimerization, AHR/ARNT Increase, slincR expression Jun 30, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1356 Differentiation of Myofibroblast Production of α-smooth muscle actin Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                659 Desensitization, Nicotinic acetylcholine receptor Neuronal network function, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1309 Desensitization, Nicotinic acetylcholine receptor Altered, Ca2+-calmodulin activated signal transduction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2921 Derease, testosterone levels Reduction, Plasma 17beta-estradiol concentrations May 22, 2023 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2925 Derease, testosterone levels Reduction, the ratio of E2/11-KT in plasma May 22, 2023 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1798 Ionizing Energy Increase mutations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1799 Ionizing Energy Increase chromosomal aberrations Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2379 Ionizing Energy Increased, Reactive oxygen species May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2380 Ionizing Energy Increase, DNA Damage May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2390 Ionizing Energy Increased, Oxidative Stress May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2392 Ionizing Energy Altered, Meiotic chromosome dynamics May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2393 Ionizing Energy Decreased spermatogenesis May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2394 Ionizing Energy impaired, Fertility May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2395 Ionizing Energy Decrease of egg production and cummulative fecundity May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2396 Ionizing Energy Decreased, Population size May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2397 Ionizing Energy Increase, Oocyte apoptosis May 14, 2021 May 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1977 Energy Deposition Increase, DNA strand breaks Aug 26, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1981 Energy Deposition Increase, Mutations Aug 29, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1982 Energy Deposition Increase, Chromosomal aberrations Aug 29, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1983 Energy Deposition Increase, lung cancer Aug 29, 2019 Jul 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2548 Energy Deposition Increased, Reactive oxygen species Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2552 Energy Deposition Increase, DNA Damage Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2557 Energy Deposition Increase, ROS production Feb 4, 2022 Feb 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2604 Energy Deposition Microcephaly Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2616 Energy Deposition Increase in RONS Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2769 Energy Deposition Oxidative Stress Sep 28, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2770 Energy Deposition Vascular remodeling Sep 28, 2022 Sep 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2779 Energy Deposition Altered, Nitric Oxide Levels Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2780 Energy Deposition Increase, Endothelial Dysfunction Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2785 Energy Deposition Occurrence, Vascular Remodeling Oct 17, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2809 Energy Deposition Modified Proteins Dec 16, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2813 Energy Deposition Increase, Oxidative DNA damage Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2814 Energy Deposition Increase, Cell Proliferation Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2815 Energy Deposition Cataracts Dec 18, 2022 Mar 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2832 Energy Deposition Tissue resident cell activation Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2837 Energy Deposition Abnormal Neural Remodeling Jan 25, 2023 Feb 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2838 Energy Deposition Impairment, Learning and memory Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2847 Energy Deposition Altered Bone Cell Homeostasis Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2848 Energy Deposition Bone Remodeling Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2849 Energy Deposition Bone Loss Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3133 Depletion, mtDNA Mitochondrial dysfunction Feb 28, 2024 Feb 28, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2878 Depletion, GSH Increased, Reactive oxygen species Apr 5, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1181 Depletion, energy reserves Delayed, Sexual maturity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1185 Depletion, energy reserves Increase, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1182 Delayed, Sexual maturity Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2739 Delay, Ovarian maturation Increase, Body volume of female adults Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2740 Delay, Ovarian maturation Increase, sex ratio (F/M) Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              447 Delay, Developmental GABA shift Synaptogenesis, Decreased Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                907 Degeneration of dopaminergic neurons of the nigrostriatal pathway Neuroinflammation Nov 29, 2016 Oct 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                910 Degeneration of dopaminergic neurons of the nigrostriatal pathway Parkinsonian motor deficits Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3077 Degeneration of dopaminergic neurons of the nigrostriatal pathway impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1383 Defect of Embryogenesis Reproductive failure Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2938 Decreased, Viable Offspring Decrease, Population growth rate Jun 2, 2023 Sep 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                334 Decreased, VegfR2 Inhibition, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  768 Decreased, Uptake of inorganic iodide Decrease, Serum thyroid hormone (T4/T3) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2421 Decreased, Uptake of inorganic iodide TH synthesis, Decreased Jul 7, 2021 Jul 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1164 Decreased, Triiodothyronine (T3) in tissues Altered, Amphibian metamorphosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2238 Decreased, Triiodothyronine (T3) in tissues Increased, Thyroid-stimulating hormone (TSH) Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2239 Decreased, Triiodothyronine (T3) in tissues Altered, TH-dependent gene expression Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1027 Decreased, Triiodothyronine (T3) Reduced, Posterior swim bladder inflation Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1035 Decreased, Triiodothyronine (T3) Reduced, Anterior swim bladder inflation Nov 29, 2016 Oct 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2373 Decreased, Triiodothyronine (T3) Altered, retinal layer structure May 11, 2021 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2376 Decreased, Triiodothyronine (T3) Decreased, Eye size May 11, 2021 Jun 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2378 Decreased, Triiodothyronine (T3) Altered, Photoreceptor patterning May 11, 2021 Oct 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1142 Decreased, Thyroxine (T4) in tissues Altered, Amphibian metamorphosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1163 Decreased, Thyroxine (T4) in tissues Decreased, Triiodothyronine (T3) in tissues Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          730 Decreased, Testosterone binding to androgen receptor (hypothalamus) Increase, Hyperplasia (Leydig cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            744 Decreased, Testosterone binding to androgen receptor (hypothalamus) Increased, Luteinizing hormone (LH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1009 Decreased, Synthesis of molting fluid proteases Decrease, Digestion of old cuticle Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1001 Decreased, synthesis and secretion of molting fluid proteases Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1434 Decreased, synaptic release Decreased, extracellular serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                831 Decreased, Sodium reabsorption Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1243 Decreased, sodium conductance 2 Decreased, Ionotropic GABA receptor chloride channel conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1244 Decreased, sodium conductance 2 Decreased, GABA release Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  586 Decreased, Sodium conductance 1 Reduced, swimming speed Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  594 Decreased, Sodium conductance 1 Increased, Atrioventricular block and bradycardia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  646 Decreased, sheltering Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1065 Decreased, serum T4/T3 Increased, Thyroid-stimulating hormone (TSH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1426 Decreased, serotonin transporter activity Increased, intracellular sodium (Na+) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1427 Decreased, serotonin transporter activity Increased, intracellular chloride (Cl-) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1428 Decreased, serotonin transporter activity Decreased, extracellular Na+ Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1429 Decreased, serotonin transporter activity Decreased, extracellular chloride (Cl-) Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1430 Decreased, serotonin transporter activity Increased, extracellular serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1431 Decreased, serotonin transporter activity Decreased, intracellular serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2635 Decreased, Reproductive Success Decrease, Population growth rate Apr 6, 2022 Apr 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    830 Decreased, Renal plasma flow Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    832 Decreased, Renal ability to dilute urine Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    682 Decreased, Prostaglandin F2alpha synthesis, ovary Reduced, Prostaglandin F2alpha concentration, plasma Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1138 Decreased, Prostaglandin F2alpha concentration, plasma Occurrence, renal ischemia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    733 Decreased, Prolactin Increased, Estrogen receptor (ER) activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    772 Decreased, Progesterone from corpus luteum Increase, Hyperplasia (glandular epithelial cells of endometrium) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    878 Decreased, PPARalpha transactivation of gene expression Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Nov 29, 2016 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      879 Decreased, PPARalpha transactivation of gene expression Decreased, Mitochondrial Fatty Acid Beta Oxidation Nov 29, 2016 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        880 Decreased, PPARalpha transactivation of gene expression Decreased, Ketogenesis (production of ketone bodies) Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1748 Decreased, PPARalpha transactivation of gene expression Fatty Acid Beta Oxidation, Decreased Jun 11, 2018 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        260 Decreased, PPAR-gamma activation Decreased, HSD17B10 expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3093 Decreased, PPAR-gamma activation Alteration, lipid metabolism Oct 18, 2023 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        259 Decreased, PPAR-beta activation Decreased, HSD17B10 expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        257 Decreased, PPAR-alpha activation Decreased, HSD17B10 expression Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2042 Decreased, PPAR-alpha activation Increased, Liver Steatosis Feb 22, 2020 Feb 22, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1491 Decreased, Population trajectory Increased Mortality Apr 18, 2017 Apr 18, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            881 Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Decreased, Mitochondrial Fatty Acid Beta Oxidation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              503 Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1433 Decreased, packaged serotonin Decreased, synaptic release Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2803 Decrease overall oxygen binding capacity (methemocyanin formation) Increase, hemocyanin mRNA Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1084 Decreased, Ovarian E2 Increased, secretion of GnRH from hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1085 Decreased, Ovarian E2 Decrease, E2 blood concentrations at hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                212 Decreased, Nitric Oxide Decreased, Long-term potentiation (LTP) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1448 Decreased, neuroplasticity Increased, agitation Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1449 Decreased, neuroplasticity Increased, depression Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                634 Decreased, Neuronal network function in adult brain Impairment, Learning and memory Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2656 Decreased, Neuronal network function in adult brain Sensory axonal peripheral neuropathy May 16, 2022 May 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3072 Decreased, Neuronal network function in adult brain Neurological disorder Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3073 Decreased, Neuronal network function in adult brain Neuroinflammation Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3074 Decreased, Neuronal network function in adult brain Degeneration of dopaminergic neurons of the nigrostriatal pathway Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3076 Decreased, Neuronal network function in adult brain impaired, Learning and memory Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1538 Decreased, mucous Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1535 Decreased, mucosal blood flow Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  190 Decreased, Mitochondrial fatty acid beta-oxidation Accumulation, Fatty acid Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  617 Decreased, Mitochondrial fatty acid beta-oxidation Increased, Liver Steatosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2931 Decreased, Mitochondrial fatty acid beta-oxidation Mitochondrial dysfunction EMPTY May 25, 2023 May 25, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3159 Decreased, Mitochondrial fatty acid beta-oxidation Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3209 Decreased, Mitochondrial fatty acid beta-oxidation Disrupted Lipid Storage May 8, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      882 Decreased, Mitochondrial Fatty Acid Beta Oxidation Decreased, Ketogenesis (production of ketone bodies) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2040 Decreased, Mitochondrial Fatty Acid Beta Oxidation Increased, Liver Steatosis Feb 22, 2020 Feb 22, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2264 Decreased, Mitochondrial Fatty Acid Beta Oxidation Accumulation, Triglyceride Jan 15, 2021 Jan 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          805 Decreased, mevalonate Decreased, cholesterol Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2631 Decreased, Maturation Inducing Steroids Surge by Granulosa cells Impaired, Oocyte maturation and ovulation Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          389 Decreased, Lymphocytes Increased, Disease susceptibility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            390 Decreased, Lymphocytes Suppression, Immune system Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            651 Decreased, locomotion Increased, predation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1109 Decreased, LH Surge from anterior pituitary interruption, Ovulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1110 Decreased, LH Surge from anterior pituitary prolonged, estrus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            883 Decreased, Ketogenesis (production of ketone bodies) Not Increased, Circulating Ketone Bodies Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1660 Decreased, Ketogenesis Accumulation, Fatty acid Aug 31, 2017 Aug 31, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1432 Decreased, intracellular serotonin Decreased, packaged serotonin Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1554 Decreased, intracellular chloride Activated, membrane depolarization Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2867 decreased, IQ increased, Economic Burden Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3174 Decreased, INSL3 Impaired inguinoscrotal phase Mar 20, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            577 Decreased, Hydrogen peroxide production Reduced, Antiseptic incorporated in food Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            154 Decreased, HSD17B10 expression Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2629 Decreased, Gonadotropins Decreased , Androgen and Progestin Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1108 Decreased, GnRH pulsatility/release in hypothalamus Decreased, LH Surge from anterior pituitary Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            576 Decreased, Glucose oxidase enzyme activity Decreased, Hydrogen peroxide production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            829 Decreased, Glomerular filtration Occurrence, Kidney toxicity Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3234 Decreased, Glomerular filtration Increased, Kidney Failure Jun 6, 2024 Jun 6, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1188 Decreased, gametogenesis Decreased, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1245 Decreased, GABA release Decreased, Chloride conductance Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1552 Decreased, GABA Reduced, GABA-A receptor activation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2377 Decreased, Eye size Altered, Visual function May 11, 2021 Jan 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2406 Decreased, Eye size Increased Mortality May 28, 2021 May 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1435 Decreased, extracellular serotonin Increased, 5-HT3 Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1436 Decreased, extracellular serotonin Inactivated, 5-HTR Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1437 Decreased, extracellular serotonin Activation, 5-HT2A Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1519 Decreased, extracellular serotonin Decreased, synaptic release May 30, 2017 May 30, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1121 Decreased, Dopaminergic activity Increased, prolactin secretion Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    537 Decreased, DHB4/HSD17B4 Inhibition, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2072 Decreased, cholesterol Decreased, 11KT Mar 23, 2020 May 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3201 Decreased, cholesterol Decrease, testosterone levels Apr 25, 2024 Apr 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3167 Decreased COUP-TFII in Leydig cells Decreased steroidogenesis, Decreased Activity of Steroidogenic Enzymes Mar 20, 2024 Apr 16, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    62 Decreased, Calcium influx Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      347 Decreased, Calcium influx BDNF, Reduced Nov 29, 2016 Jun 13, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1101 Decreased, bile flow Increased, cholestasis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1540 Decreased, bicarbonate Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2870 decreased, Bcl-2 Cell injury/death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2873 decreased, Bcl-2 Increase, Cell death Apr 4, 2023 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        801 Decreased, Aromatase (Cyp19a1) mRNA Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1248 Decreased, Apoptosis (Epithelial Cells) Increased, Ductal Hyperplasia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2914 Decreased, Apoptosis (Epithelial Cells) Alterations, Cellular proliferation / hyperplasia May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        645 Decreased, anxiety Decreased, sheltering Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1542 Decreased, angiogenesis Activated, gastric ulcer formation Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        729 Decreased, Androgen receptor activity Decreased, Testosterone binding to androgen receptor (hypothalamus) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2630 Decreased , Androgen and Progestin Decreased, Maturation Inducing Steroids Surge by Granulosa cells Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2477 Decreased, atRA concentration Oocyte meiosis, disrupted Sep 10, 2021 Feb 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2561 Decreased, atRA concentration Disruption, Progenitor cells of second heart field Feb 8, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1530 Decreased, 5-HT3 Increased, seizure Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        9 Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity Decreased, Mitochondrial fatty acid beta-oxidation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2076 Decreased, 11KT Impaired, Spermatogenesis Apr 16, 2020 Apr 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2165 Decreased, 11KT Decrease, Fertility Jul 21, 2020 Jul 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2166 Decreased, 11KT Decreased spermatogenesis Jul 21, 2020 Jul 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3168 Decreased steroidogenesis, Decreased Activity of Steroidogenic Enzymes Decrease, testosterone levels Mar 20, 2024 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3171 Decreased steroidogenesis, Decreased Activity of Steroidogenic Enzymes Decrease, DHT level Mar 20, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2161 Decreased spermatogenesis impaired, Fertility Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2388 Decreased spermatogenesis Decrease of egg production and cummulative fecundity May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2620 Decreased spermatogenesis Decrease, Fecundity Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2623 Decreased spermatogenesis Decrease, Reproduction Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2624 Decreased spermatogenesis Decrease, Population growth rate Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1650 Decreased sperm quantity or quality in the adult, Decreased fertility impaired, Fertility Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2611 Decrease,SIRT1(sirtuin 1) levels Increased activation, Nuclear factor kappa B (NF-kB) Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1615 decreased reward decreased DNA methylation of tyrosine hydroxylase Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1616 decreased reward decreased methylation of dopamine transporter promoter Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1617 decreased reward decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1916 retinoic acid plasma retionic acid May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1812 Decreased proximal tubular vectorial transport Chemical induced Fanconi syndrome Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1766 Protection against oxidative stress, decreased Oxidative Stress Sep 13, 2018 Feb 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3111 Decreased proliferation of cortical NPCs Altered brain morphology Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3125 Decreased proliferation of cortical NPCs RAR agonism Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3126 Decreased proliferation of cortical NPCs Reduced cortical thickness Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1917 plasma retionic acid Altered, Photoreceptor patterning May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2278 Decreased plasma Cortisol level decreased oocyte maturation Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2293 decreased oocyte maturation impaired, Fertility Mar 26, 2021 Mar 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1811 Decreased Na/K ATPase activity Decreased proximal tubular vectorial transport Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2787 Decreased Na/K ATPase activity Increase, Cell membrane depolarization Oct 19, 2022 Oct 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1619 decreased methylation of dopamine transporter promoter obesity Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1621 decreased methylation of dopamine transporter promoter decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1814 Decreased IL-1 production Impaired IL-1 signaling Dec 25, 2018 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1824 Decreased IL-1 production Suppressed MyD88 Jan 6, 2019 Jan 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2700 decrease folate Neural tube defects Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1614 decreased dopamine decreased reward Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1618 decreased DNA methylation of tyrosine hydroxylase obesity Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1620 decreased DNA methylation of tyrosine hydroxylase decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2744 Decrease, Tyrosine Decrease, dopa decarboxylase Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                399 Decrease, Translocator protein (TSPO) Reduction, Testosterone synthesis in Leydig cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  437 Decrease, Translocator protein (TSPO) Reduction, Cholesterol transport in mitochondria Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1888 Decrease, Transgenerational DNA methylation Increase, Gene expression Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2129 decrease, transcription of genes by AR AGD, decreased May 11, 2020 May 11, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1934 Decrease, testosterone level Decrease, DHT level Jun 3, 2019 Jun 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1936 Decrease, testosterone level Decrease, AR activation Jun 3, 2019 Jun 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2126 Decrease, testosterone levels Decrease, DHT level May 11, 2020 Oct 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2131 Decrease, testosterone levels Decrease, AR activation May 11, 2020 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3169 Decrease, testosterone levels Epididymal agenesis Mar 20, 2024 Apr 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3202 Decrease, testosterone levels malformed, Male reproductive tract Apr 25, 2024 Apr 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3205 Decrease, testosterone levels Malformation, Male reproductive tract May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3206 Decrease, testosterone levels Increase, Luteinizing hormone (LH) May 1, 2024 May 1, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3213 Decrease, testosterone levels Reduction, Plasma 17beta-estradiol concentrations May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3214 Decrease, testosterone levels Reduction, the ratio of E2/11-KT in plasma May 8, 2024 May 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3225 Decrease, testosterone levels Decreased sperm quantity or quality in the adult, Decreased fertility May 24, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3227 Decrease, testosterone levels Increased, Leutinizing hormone (LH) May 24, 2024 May 24, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1547 Decrease, surfactant Reduced, mucosal defense Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        436 Decrease, Steroidogenic acute regulatory protein (STAR) Reduction, Cholesterol transport in mitochondria Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2685 Decrease, sox9 expression Smaller and morphologically distorted facial cartilage structures Jun 30, 2022 Oct 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2691 Decrease, sox9 expression Altered, Cardiovascular development/function Jun 30, 2022 Oct 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3060 Decrease, sox10 N/A, Neurodegeneration Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2732 Decrease, SHH second messenger production Decrease, Cell proliferation Aug 23, 2022 Nov 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2733 Decrease, SHH second messenger production Increase, Apoptosis Aug 23, 2022 Aug 23, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2957 Decrease, SHH second messenger production Apoptosis Jun 29, 2023 Jun 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2735 Decrease, SMO relocation Decrease, GLI1/2 translocation Aug 23, 2022 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          769 Decrease, Serum thyroid hormone (T4/T3) Increase, Thyroid-stimulating hormone (TSH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2336 Decrease, Reproduction Decrease, Population growth rate Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2556 Decrease, Reproduction Decreased, Population trajectory Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2756 Decrease, Prevent chitin degradation by chitinases Weak, Procuticle protection Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2180 Decrease, ATPase activity Increase, Abnormal osmoregulation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2333 Decrease, Photosystem II efficiency Decrease, Photosynthesis Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1737 Decrease, PSII activity Decrease, Photosynthesis May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1740 Decrease, PSII activity Increase, ROS May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1667 Decrease, Photosynthesis Decrease, Glycolysis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2334 Decrease, Photosynthesis Decrease, ATP production Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2343 Decrease, Photosynthesis Decrease, ATP synthase activity Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2726 Decrease, outgrowth OFC Jul 28, 2022 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1669 Decrease, OXPHOS Decrease, Mitochondrial ATP production Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1810 Decrease, OXPHOS Decreased Na/K ATPase activity Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2095 Decrease, OXPHOS Decrease, ATP pool Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2346 Decrease, OXPHOS Decrease, ATP synthase activity Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2713 Decrease, OXPHOS Oxidative Stress Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        544 Decrease, Ovulation Reduction, Cumulative fecundity and spawning Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          687 Decrease, Ovulation Reduced, Reproductive Success Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1471 Decrease, Ovulation Decrease, Fertility Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1753 Decrease, Ovulation Decrease, Fecundity Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2114 Decrease, Oogenesis (F3) Decrease, Fecundity (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1470 Decrease, Oogenesis Decrease, Ovulation Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1752 Decrease, Oogenesis Decrease, Fecundity Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Thermal stress leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2586 Decrease, Oogenesis Decrease, Reproduction Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2588 Decrease, Oogenesis Reduction, Cumulative fecundity and spawning Mar 1, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  559 Decrease, Number of worker bees Death/Failure, Colony Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  573 Decrease, Number of worker bees impaired, Hive thermoregulation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2758 Decrease, New cuticle secretion Increase, Incomplete ecdysis Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2098 Decrease, Neutral lipids Decrease, ATP pool Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2094 Decrease, MMP Decrease, OXPHOS Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2347 Decrease, MMP Increase, Programmed cell death Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3163 Decrease, MMP Mitochondrial dysfunction Mar 14, 2024 Mar 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1601 Decrease, Mitochondrial ATP production Decrease, Oogenesis Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1670 Decrease, Mitochondrial ATP production Decrease, Leaf cell mitosis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1682 Decrease, Mitochondrial ATP production Increase, Cytotoxicity (renal tubular cell) Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Renal protein alkylation leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1739 Decrease, Mitochondrial ATP production Decrease, Growth May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1750 Decrease, Mitochondrial ATP production Increase, Apoptosis Jun 12, 2018 Jun 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1873 Decrease, Mitochondrial ATP production Increase, Necrosis Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2551 Decrease, Mitochondrial ATP production Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2823 Decrease, Mitochondrial ATP production Decrease, Cardiac contractility Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3061 Decrease, mbp N/A, Neurodegeneration Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1666 Decrease, Light harvest capacity Decrease, Photosynthesis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1672 Decrease, Leaf development Increase, Growth hormone Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2283 Decrease, Leaf development Decrease, Growth Feb 16, 2021 Feb 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2335 Decrease, Leaf development Decrease, Reproduction Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1671 Decrease, Leaf cell mitosis Decrease, Leaf development Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2753 Decrease, knickkopf gene Decrease, Chitin laminar organization Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2754 Decrease, knickkopf gene Decrease, Prevent chitin degradation by chitinases Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              886 Decrease, Intracellular pH Increase, Cytotoxicity Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              791 Decrease, Incorporation of active iodide into iodotyrosines Decrease, Serum thyroid hormone (T4/T3) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                649 Decrease, histaminergic neuron excitation N/A, sedation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1643 Decrease, histaminergic neuron excitation Impairment, Learning and memory Aug 11, 2017 Aug 11, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2111 Decrease, Heritable DNA methylation (F3) Increase, Casp transcription (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2169 Decrease, Growth Decrease, Population growth rate Oct 8, 2020 Oct 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2804 Decrease, Growth Decreased, Reproductive Success Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1668 Decrease, Glycolysis Decrease, OXPHOS Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1738 Decrease, Glycolysis Decrease, Mitochondrial ATP production May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2529 Decrease, GLUT4 Decrease, Glucose uptake Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2530 Decrease, Glucose uptake Abnormal, Glucose homeostasis Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2795 Decrease, Glucose pool Decrease, Cell proliferation Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2102 Decrease, Global DNA methylation Increase, Casp transcription Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2110 Decrease, Global DNA methylation Decrease, Heritable DNA methylation (F3) Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2721 Decrease, GLI1/2 translocation Decrease, GLI1/2 target gene expression Jul 28, 2022 Jun 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2722 Decrease, GLI1/2 target gene expression Decrease, Cell proliferation Jul 28, 2022 Nov 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2723 Decrease, GLI1/2 target gene expression Increase, Apoptosis Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2731 Decrease, GLI1/2 target gene expression Decrease, SHH second messenger production Aug 23, 2022 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2805 Decrease, GLI1/2 target gene expression Decrease, outgrowth Nov 17, 2022 Nov 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2882 Decrease, GLI1/2 target gene expression Apoptosis Apr 6, 2023 May 1, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1472 Decrease, Fertility Decrease, Population growth rate Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2115 Decrease, Fecundity (F3) Decrease, Population growth rate Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            135 Decrease, Fecundity Decline, Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1886 Decrease, Fecundity Decrease, Population growth rate Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Thermal stress leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2621 Decrease, Fecundity Decrease, Reproduction Mar 28, 2022 Mar 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2208 Decrease, FAO Decrease, ATP pool Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1995 Decease, expression of GnRHR Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1349 Decrease, Excitatory postsynaptic potential Decrease, Abdominal muscle contraction Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3059 Decrease, elavl3 N/A, Neurodegeneration Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1348 Decrease, Ecdysis motoneuron bursts Decrease, Excitatory postsynaptic potential Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1087 Decrease, E2 blood concentrations at hypothalamus Increased, secretion of GnRH from hypothalamus Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2745 Decrease, dopa decarboxylase Increase, Defects in tanning of new cuticle Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1881 Decrease, DHT level Reduction, Plasma 17beta-estradiol concentrations Apr 18, 2019 Apr 18, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1935 Decrease, DHT level Decrease, AR activation Jun 3, 2019 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                3172 Decrease, DHT level Impaired, urethral tube closure Mar 20, 2024 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1011 Decrease, Digestion of old cuticle Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2171 Decrease, Digestion of old cuticle Increase, Premature molting Oct 21, 2020 Oct 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1743 Decrease, Cuticular chitin content Increase, Premature molting May 24, 2018 Feb 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1600 Decrease, Coupling of OXPHOS Decrease, Mitochondrial ATP production Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2175 Decrease, Coupling of OXPHOS Decrease, ATP synthase activity Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2182 Decrease, Coupling of OXPHOS Increase, Complex III dysfunction Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2188 Decrease, Coupling of OXPHOS Increase, Complex I dysfunction Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2203 Decrease, Coupling of OXPHOS Decrease, ATP pool Nov 12, 2020 Jul 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2219 Decrease, Coupling of OXPHOS Increase, Oxygen consumption Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2763 Decrease, Coupling of OXPHOS Increase, Cytosolic Ca Sep 13, 2022 Sep 13, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2793 Decrease, Coupling of OXPHOS Increase, Glycolysis Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2796 Decrease, Coupling of OXPHOS Increase, Mitochondrial swelling Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1000 Decrease, Circulating ETH Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1008 Decrease, Circulating ETH Decrease, Abdominal muscle contraction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1346 Decrease, Circulating ETH Decrease, Circulating CCAP Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1347 Decrease, Circulating CCAP Decrease, Ecdysis motoneuron bursts Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1665 Decrease, Chlorophyll synthesis Decrease, Light harvest capacity Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2755 Decrease, Chitin laminar organization Weak, Procuticle protection Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2205 Decrease, Cell proliferation Decrease, Growth Nov 12, 2020 Jul 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2405 Decrease, Cell proliferation Decreased, Eye size May 28, 2021 Aug 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2724 Decrease, Cell proliferation Decrease, outgrowth Jul 28, 2022 May 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1759 Decrease, Cardiac ejection fraction Heart failure Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1758 Decrease, Cardiac contractility Decrease, Cardiac ejection fraction Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2824 Decrease, Cardiac contractility Heart failure Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3176 Decrease, Cardiac contractility Decrease LV function Apr 3, 2024 Apr 3, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1756 Decrease, Calcium currents Decrease, Calcium binding to Troponin C Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1760 Decrease, Calcium currents Disruption, Intracellular calcium mobilization Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1757 Decrease, Calcium binding to Troponin C Decrease, Cardiac contractility Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  793 Decrease, Bioactivation of testosterone Increased, Leutinizing hormone (LH) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2176 Decrease, ATP synthase activity Decrease, ATP pool Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2344 Decrease, ATP synthase activity Decrease, Leaf development Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1664 Decrease, ATP production Decrease, Chlorophyll synthesis Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2341 Decrease, ATP production Decrease, Leaf development Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2547 Decrease, ATP production Decrease, Reproduction Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        43 Decrease, Aromatase (Cyp19a1) Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          961 Decreased ciliated cell apoptosis Occurrence, Transdifferentiation of ciliated epithelial cells Nov 29, 2016 Aug 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2470 Decreased ciliated cell apoptosis Goblet cell metaplasia Aug 25, 2021 Aug 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1937 Decrease, AR activation Impaired inguinoscrotal phase Jun 3, 2019 Jun 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2124 Decrease, AR activation Altered, Transcription of genes by the AR May 11, 2020 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2128 Decrease, AR activation decrease, transcription of genes by AR May 11, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2820 Decrease, AR activation AGD, decreased Dec 22, 2022 Dec 22, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2828 Decrease, AR activation Hypospadias Jan 11, 2023 Jan 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor (AR) antagonism leading to hypospadias in male offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2096 Decrease, ATP pool Increase, Mortality Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2120 Decrease, ATP pool Increase, Oocyte apoptosis May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2121 Decrease, ATP pool Increase, Necrosis May 8, 2020 May 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2179 Decrease, ATP pool Decrease, ATPase activity Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2204 Decrease, ATP pool Decrease, Cell proliferation Nov 12, 2020 Dec 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2209 Decrease, ATP pool Decrease, Oogenesis Nov 25, 2020 Nov 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Thermal stress leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2214 Decrease, ATP pool Increase, Cell death Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2216 Decrease, ATP pool Increase, Fatty acid β-oxidation Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2768 Decrease, ATP pool Cell injury/death Sep 27, 2022 Sep 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2786 Decrease, ATP pool Decreased Na/K ATPase activity Oct 19, 2022 Oct 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2267 Decrease, ACAD Decreased, Mitochondrial Fatty Acid Beta Oxidation Jan 15, 2021 Jan 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1010 Decrease, Abdominal muscle contraction Increase, Incomplete ecdysis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2752 Decrease, 20-hydroxyecdysone Decrease, knickkopf gene Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      443 Thyroidal Iodide, Decreased T4 in serum, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        872 Thyroidal Iodide, Decreased TH synthesis, Decreased Nov 29, 2016 Jun 4, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        358 Synaptogenesis, Decreased Neuronal network function, Decreased Nov 29, 2016 May 25, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        656 Synaptogenesis, Decreased Neuroinflammation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          359 Neuronal network function, Decreased Impairment, Learning and memory Nov 29, 2016 Jul 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2411 Neuronal network function, Decreased Cognitive Function, Decreased Jun 24, 2021 Aug 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2501 Neuronal network function, Decreased Memory Loss Oct 26, 2021 Oct 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2953 Neuronal network function, Decreased Neurological disorder Jun 21, 2023 Jun 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3123 Neuronal network function, Decreased autism-like behavior Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          871 GABAergic interneurons, Decreased Synaptogenesis, Decreased Nov 29, 2016 Jan 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1991 Decrease of egg production and cummulative fecundity Decline, Population trajectory Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2389 Decrease of egg production and cummulative fecundity Decreased, Population size May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1787 Decrease in mitochondrial oxidative phosphorylation Mitochondrial Injury Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1956 Decrease in mitochondrial oxidative phosphorylation Mitochondrial dysfunction Jun 15, 2019 Jun 15, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3147 Decompartmentalization Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1265 Decline, Population Alteration, Food-web structures Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3108 decline, neural progenitor cells Microcephaly Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            277 Damaging, Red blood cells; hemolysis Increase, Liver and splenic hemosiderosis Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            278 Damaging, Red blood cells; hemolysis N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            279 Damaging, Red blood cells; hemolysis Increase, RBC congestion in liver Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            839 Damage, Lipid bilayer Occurrence, Cytoplasmic vacuolization (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            840 Damage, Lipid bilayer Occurrence, Ballooning degeneration (hepatocyte) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            841 Damage, Lipid bilayer Occurrence, Cytoplasmic vacuolization (Bile duct cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            842 Damage, Lipid bilayer Occurrence, Cytoplasmic vacuolization (kupffer cell) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2440 CFTR Function, Decreased ASL Height, Decreased Jul 19, 2021 Sep 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1493 CYP7B activity, inhibition 7α-hydroxypregnenolone synthesis in the brain, decreased May 2, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1494 CYP7B activity, inhibition Locomotor activity, decreased May 2, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3230 CYP450 Upregulation Oxidative Stress Jun 4, 2024 Jun 4, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1726 CYP2E1 Activation Oxidative Stress in Brain Apr 4, 2018 Apr 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            376 Covalent Binding, Protein Response, Keratinocytes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              377 Covalent Binding, Protein Activation, Dendritic Cells Nov 29, 2016 Nov 5, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              833 Covalent Binding, Protein Activation, Keratinocytes Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2202 Covalent Binding, Protein Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways Nov 5, 2020 Feb 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2649 Covalent Binding, Protein Increased proinflammatory mediators Apr 28, 2022 Sep 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2650 Covalent Binding, Protein Increase, Allergic Respiratory Hypersensitivity Response Apr 28, 2022 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2276 Cortisol and 11β-(OH) testosterone decreased Decreased plasma Cortisol level Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2277 Cortisol and 11β-(OH) testosterone decreased Decreased, 11KT Feb 9, 2021 Feb 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2877 Conjugation, GSH Depletion, GSH Apr 5, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1804 Reduced collagen production Smaller and morphologically distorted facial cartilage structures Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1359 Collagen Deposition Lung fibrosis Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1628 Collagen Deposition Accumulation, Collagen Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2801 Hemocyanin Bohr effect decrease behavioral change leading to possible reduced feeding opportunity Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2290 Coagulation Thrombosis and DIC Mar 25, 2021 Feb 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2313 Coagulation Oxidative Stress Apr 8, 2021 Apr 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2360 Coagulation Diminished Protective Response to ROS Apr 20, 2021 Oct 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    550 Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Tumorigenesis, Hepatocellular carcinoma Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2442 CBF, Decreased MCC, Decreased Jul 19, 2021 Mar 24, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1314 Chronic, Mucus hypersecretion Decreased lung function Nov 29, 2016 Aug 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2069 Chronic ROS Porcupine-induced Wnt secretion and Wnt signaling activation Mar 23, 2020 May 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1613 chronic high fat diet decreased dopamine Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      995 Changes/Inhibition, Cellular Homeostasis and Apoptosis N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects Nov 29, 2016 Dec 2, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      67 Cell injury/death Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        68 Cell injury/death Activation, Stellate cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        355 Cell injury/death Synaptogenesis, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        364 Cell injury/death N/A, Neurodegeneration Nov 29, 2016 Sep 10, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        365 Cell injury/death Neuroinflammation Nov 29, 2016 Jul 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        924 Cell injury/death Release, Cytokine Nov 29, 2016 Nov 9, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1688 Cell injury/death Neuronal network function, Decreased Nov 9, 2017 Feb 5, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1718 Cell injury/death Tissue resident cell activation Feb 1, 2018 Aug 2, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1776 Cell injury/death Increased pro-inflammatory mediators Nov 12, 2018 Nov 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1830 Cell injury/death Necrotic Tissue Jan 7, 2019 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1831 Cell injury/death Activation, Tissue resident cells (Kuppfer cells) Jan 7, 2019 Jan 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1863 Cell injury/death Neurodegeneration Feb 19, 2019 Feb 19, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2767 Cell injury/death Decrease, Growth Sep 27, 2022 Sep 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2875 Cell injury/death Hippocampal Physiology, Altered Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2890 Cell injury/death Leukocyte recruitment/activation Apr 13, 2023 Apr 13, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3197 Cell injury/death Disruption of the intestinal barrier Apr 17, 2024 Apr 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3198 Cell injury/death Mitochondrial dysfunction Apr 17, 2024 Apr 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1712 Cell cycle, disrupted Apoptosis Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2791 Cell cycle, disrupted Altered, Meiotic chromosome dynamics Oct 25, 2022 Oct 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1195 Calcium cannot bind to the hydroxyapatite matrix of bone, Osteocalcin and other bone protei Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Imp Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2398 Bulky DNA adducts, increase Inadequate DNA repair May 17, 2021 May 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Bulky DNA adducts leading to mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2399 Bulky DNA adducts, increase Increase, Mutations May 17, 2021 Sep 14, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Bulky DNA adducts leading to mutations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2353 Bradykinin, activated Increased proinflammatory mediators Apr 20, 2021 Jan 14, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2355 Bradykinin, activated Hypofibrinolysis Apr 20, 2021 Jan 24, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2357 Bradykinin, activated Hyperinflammation Apr 20, 2021 Oct 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1170 Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1973 Blood extravasation into the lungs Acute inhalation toxicity Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1813 Blocking of IL-1R Impaired IL-1 signaling Dec 24, 2018 Jun 25, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1755 Blockade, L-Type Calcium Channels Decrease, Calcium currents Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2025 STAT5 inhibition Suppression of STAT5 binding to cytokine gene promoters Jan 5, 2020 Nov 3, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    330 Binding, VEGF-A Decreased, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      331 Binding, VEGF-A Inhibition, VegfR2 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        714 Binding, Tubulin Disruption, Microtubule dynamics Nov 29, 2016 May 27, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        724 Binding, Tubulin Altered, Chromosome number Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2245 Binding, Transthyretin in serum Displacement, Serum thyroxine (T4) from transthyretin Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2248 Binding, Transthyretin in serum Displacement, Serum thyroxine (T4) from carrier protein Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2269 Binding, Transthyretin in serum Increased, Clearance of thyroxine from serum Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2271 Binding, Transthyretin in serum Increased, Free serum thyroxine (T4) Jan 26, 2021 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2250 Binding, Thyroid binding globulin in serum Displacement, Serum thyroxine (T4) from carrier protein Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1683 Binding, SH/SeH proteins involved in protection against oxidative stress Mitochondrial dysfunction Nov 9, 2017 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1689 Binding, SH/SeH proteins involved in protection against oxidative stress Oxidative Stress Nov 9, 2017 Feb 7, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1765 Binding, SH/SeH proteins involved in protection against oxidative stress Protection against oxidative stress, decreased Sep 13, 2018 Feb 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                287 Binding, SH-/selen-proteins N/A, Interferences with SH-/selen-proteins Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1253 Binding, Immunophilins Inhibition, Calcineurin Activity Nov 29, 2016 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2605 Binding to VGSC Altered kinetics of sodium channel Mar 21, 2022 Mar 31, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2534 Binding to hERG channel Direct hERG channel blockage Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2020 Binding to estrogen receptor (ER)-α Induction of GATA3 expression Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2056 Binding to ACE2 SARS-CoV-2 cell entry Mar 2, 2020 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2286 Binding to ACE2 Neuroinflammation Feb 23, 2021 Feb 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2294 Binding to ACE2 Induced, Angiotensin (Ang) II accumulation Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2297 Binding to ACE2 Increased AngII Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2299 Binding to ACE2 ACE2 enzymatic inhibition Mar 28, 2021 Mar 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2311 Binding to ACE2 ACE2 dysregulation Mar 31, 2021 Feb 7, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2312 Binding to ACE2 Downregulation of ACE2 Mar 31, 2021 Nov 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2452 Binding to ACE2 Endothelial cell dysfunction Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2522 Binding to ACE2 ADAM17 induction Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1330 Binding, topoisomerase II MLL translocation Jan 20, 2017 Apr 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1634 Binding, topoisomerase II Increase, DSB Aug 2, 2017 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1677 Binding of substrate, endocytic receptor Disturbance, Lysosomal function Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1833 Binding of MSAs to microtubules Disturbance in microtubule dynamic instability Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  933 Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) Inhibition, NADH-ubiquinone oxidoreductase (complex I) Nov 29, 2016 Aug 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1946 Binding of inhibitor, mitochondrial complex V Mitochondrial Complex V inhibition Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1945 Binding of inhibitor, mitochondrial complex IV Mitochondrial Complex IV inhibition Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1944 Binding of inhibitor, mitochondrial complex III Increase, Mitochondrial complex III antagonism Jun 7, 2019 Jun 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3243 Binding of C6R-Derived Protein K7 Histone acetylation, increase Jun 10, 2024 Jun 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1023 Binding of antagonist, PPAR alpha stabilization, PPAR alpha co-repressor Nov 29, 2016 Jun 11, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  228 Binding of antagonist, NMDA receptors Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    229 Binding of antagonist, NMDA receptors Inhibition, NMDARs Nov 29, 2016 Jun 13, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3181 Binding of antagonist to thyroid hormone receptor TR Antagnoism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3182 Binding of antagonist to glucocorticoid hormone receptor GR antagonism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    360 Binding of agonist, NMDARs Overactivation, NMDARs Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      919 Binding of agonist, Ionotropic glutamate receptors Overactivation, NMDARs Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2304 Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) Increase, ROS production Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2319 Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) Increased, Reactive oxygen species Apr 10, 2021 Apr 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        3184 Binding of (ant)agonist to PPAR alpha Binding of antagonist to thyroid hormone receptor Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3185 Binding of (ant)agonist to PPAR alpha PPAR alpha activity, altered Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3188 Binding of (ant)agonist to PPAR alpha Cholesterol metabolism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3195 Binding of (ant)agonist to PPAR alpha Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3183 Binding of (ant)agonist to liver X receptor LXR activity, altered Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3187 Binding of (ant)agonist to liver X receptor Cholesterol metabolism Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          666 Binding at picrotoxin site, iGABAR chloride channel Reduction, Ionotropic GABA receptor chloride channel conductance Nov 29, 2016 Apr 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          877 Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain Decreased, PPARalpha transactivation of gene expression Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            248 Bile accumulation, Pathological condition Activation of specific nuclear receptors, Transcriptional change Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            928 Bile accumulation, Pathological condition Release, Cytokine Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            930 Bile accumulation, Pathological condition Production, Reactive oxygen species Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3199 beta-catenin activation EMT Apr 23, 2024 Apr 23, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2192 Reactive Metabolite Mitochondrial dysfunction EMPTY Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2194 Reactive Metabolite Immune cell activation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3151 Reactive Metabolite Mitochondrial dysfunction Mar 13, 2024 Mar 13, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2198 Apoptotic cell death Increase in inflammation Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1368 Apoptosis Reproductive failure Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1713 Apoptosis Testicular atrophy Jan 21, 2018 Jan 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1735 Apoptosis Spermatocyte depletion May 22, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1867 Apoptosis Activation, hepatic stellate cells Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1869 Apoptosis Liver Injury Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2191 Apoptosis Increase, Tissue/organ damage Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2577 Apoptosis tumor growth Feb 15, 2022 Mar 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2675 Apoptosis Emphysema Jun 17, 2022 Jun 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2792 Apoptosis Decrease, outgrowth Oct 27, 2022 Apr 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2967 Apoptosis N/A, Neurodegeneration Jul 18, 2023 Apr 11, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3106 Apoptosis decline, neural progenitor cells Jan 10, 2024 Jan 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1194 Anticoagulant rodenticide interferes with gamma-carboxyglutamate formation, Inhibition of p Calcium cannot bind to the hydroxyapatite matrix of bone, Osteocalcin and other bone protei Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1986 Antagonism,LH receptor Reduction, Progesterone synthesis Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1947 TR Antagnoism Hippocampal gene expression, Altered Jun 8, 2019 Jun 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1948 TR Antagnoism Cognitive Function, Decreased Jun 8, 2019 Jun 8, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3186 TR Antagnoism Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3193 TR Antagnoism Hypomyelination Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2720 Antagonism Smoothened Decrease, GLI1/2 translocation Jul 28, 2022 Jul 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2734 Antagonism Smoothened Decrease, SMO relocation Aug 23, 2022 May 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2894 Antagonism Smoothened OFC Apr 14, 2023 May 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1061 Antagonism, Histamine Receptor (H2) Decrease, histaminergic neuron excitation Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      129 Antagonism, Estrogen receptor Reduction, Vitellogenin synthesis in liver Nov 29, 2016 Nov 30, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2613 Antagonism, Estrogen receptor EMT Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3120 Antagonism, Estrogen receptor inhibition, EKR1/2 signaling pathway Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2123 Antagonism, Androgen receptor AGD, decreased May 11, 2020 Aug 7, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2130 Antagonism, Androgen receptor Decrease, AR activation May 11, 2020 Apr 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to hypospadias in male offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2133 Antagonism, Androgen receptor nipple retention, increased May 11, 2020 Jan 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2201 Antagonism, Androgen receptor Altered, Transcription of genes by the AR Nov 2, 2020 Feb 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2519 Degradation of Ang-II reduced Induced, Angiotensin (Ang) II accumulation Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2518 Ang (1-7) levels reduced Degradation of Ang-II reduced Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            3032 Angiogenesis dysfunction Increase, Vascular disrupting effects Aug 28, 2023 Aug 28, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2983 Angiogenesis disfunction Increase, Vascular disrupting effects Aug 19, 2023 Aug 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1971 Alveolar reopening Loss of barrier function Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2173 Alveolar reopening Loss of alveolar capillary membrane integrity Oct 22, 2020 Oct 22, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1970 Alveolar collapse Alveolar reopening Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1974 Alveolar collapse Reduced tidal volume Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2284 Alveolar collapse Loss of alveolar capillary membrane integrity Feb 16, 2021 Feb 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2285 Alveolar collapse Impaired lung function Feb 16, 2021 Feb 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2371 Alveolar collapse Decreased lung function Apr 27, 2021 Apr 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3192 Altered, white brain matter Impairment, Learning and memory Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1919 Altered, Visual function Decline, Population May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2143 Altered, Visual function Decrease, Population growth rate May 25, 2020 May 25, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2375 Altered, Visual function Increased Mortality May 11, 2021 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        316 Altered, Transcription of genes by the AR Feminisation or incomplete development, Primary and accessory male sex organs Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        317 Altered, Transcription of genes by the AR Alteration, Wnt pathway Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2127 Altered, Transcription of genes by the AR AGD, decreased May 11, 2020 May 11, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2132 Altered, Transcription of genes by the AR nipple retention, increased May 11, 2020 May 11, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2273 Altered, Transcription of genes by the AR Reduced granulosa cell proliferation Jan 28, 2021 Apr 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2909 Altered, Transcription of genes by the AR Increase, Androgen receptor May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2244 Altered, TH-dependent gene expression Altered, Amphibian metamorphosis Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2374 Altered, retinal layer structure Altered, Visual function May 11, 2021 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1299 Altered, Protein Production Increased, Oxidative Stress Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1303 Altered, Protein Production Increased, Proliferation (Endothelial cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1304 Altered, Protein Production Decreased, Apoptosis (Epithelial Cells) Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1305 Altered, Protein Production Increased, Motility Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1918 Altered, Photoreceptor patterning Altered, Visual function May 22, 2019 Jun 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2789 Altered, Nitric Oxide Levels Increase, Endothelial Dysfunction Oct 20, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        384 Altered, Neurophysiology Cognitive Function, Decreased Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        203 Altered, Neuroanatomy Altered, Neurophysiology Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        738 Altered, Meiotic chromosome dynamics Altered, Chromosome number Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2383 Altered, Meiotic chromosome dynamics Increase, Oocyte apoptosis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2384 Altered, Meiotic chromosome dynamics Decreased spermatogenesis May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2391 Altered, Meiotic chromosome dynamics Ionizing Energy May 12, 2021 May 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2554 Altered, Meiotic chromosome dynamics Increase, Pollen abnormal Jan 21, 2022 Jan 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2468 Altered, inner ear development Reduced, Hearing Aug 23, 2021 Aug 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1298 Altered, Gene Expression Altered, Protein Production Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1807 Altered, Gene Expression Altered differentiation Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          723 Altered, Chromosome number Increase, Aneuploid offspring Nov 29, 2016 Dec 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3189 Cholesterol metabolism Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          3196 Cholesterol metabolism LXR activity, altered Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          977 Altered, Cardiovascular development/function Increase, Pericardial edema Nov 29, 2016 Jun 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1352 Altered, Cardiovascular development/function Increase, Mortality Feb 9, 2017 Feb 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1567 Altered, Cardiovascular development/function Increase, Early Life Stage Mortality Jun 9, 2017 Mar 23, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1310 Altered, Ca2+-calmodulin activated signal transduction Impairment, Learning and memory Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              702 Altered, Action Potential Increased, cardiac arrthymia Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2773 Altered Signaling Altered, Nitric Oxide Levels Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2775 Altered Signaling Increase, Endothelial Dysfunction Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2840 Altered Signaling Abnormal Neural Remodeling Jan 25, 2023 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2843 Altered Signaling Altered Bone Cell Homeostasis Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              3194 LXR activity, altered Reduced number of oligodendrocytes Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2641 Altered expression of NRF2 pathway-dependent genes ER stress Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2642 Altered expression of NRF2 pathway-dependent genes Increased, Oxidative Stress Apr 8, 2022 Apr 8, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              16 Altered expression of AHR/ARNT pathway-dependent genes Altered, Cardiovascular development/function Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                17 Altered expression of AHR/ARNT pathway-dependent genes Up Regulation, CYP1A1 Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1269 Altered expression of hepatic CAR-dependent genes Increase, cell proliferation (hepatocytes) Nov 29, 2016 Dec 21, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  3110 Altered expression of cell cycle genes Decreased proliferation of cortical NPCs Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1808 Altered differentiation Neural tube defects Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2603 Altered differentiation Microcephaly Mar 17, 2022 Mar 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    3112 Altered brain morphology Impairment, Learning and memory Jan 14, 2024 Jan 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory