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Key Events

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ID Title Biological organization Creation Date Last Updated AOPs
2157 Abnormal Cardiac Structure and Function Organ Jul 31, 2023 Jul 31, 2023
    1253 MLL chromosomal translocation Cellular Dec 16, 2016 Aug 1, 2022
    • Inhibitor binding to topoisomerase II leading to infant leukaemia
    281 Thyroxine (T4) in serum, Decreased Tissue Nov 29, 2016 Oct 10, 2022
    • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
    • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
    • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, 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
    • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
    • 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
    • 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
    • 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)
    • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the 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 liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
    • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
    1094 , hyperuricemia Nov 29, 2016 Nov 29, 2016
      1027 , Learning and memory, impairment Nov 29, 2016 Nov 29, 2016
        1796 11β-hydroxylase inhibition Molecular Jul 13, 2020 Jul 13, 2020
        • Inhibition of 11β-hydroxylase leading to decresed population trajectory
        1387 7α-hydroxypregnenolone synthesis in the brain, decreased Cellular 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
        382 Aberrant, Dendritic morphology Cellular Nov 29, 2016 Sep 16, 2017
        • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
        2208 Aberrant, synaptic formation and plasticity Organ Jan 25, 2024 Jan 25, 2024
        • Estrogen antagonism leading to increased risk of autism-like behavior
        2166 Abnormal expression of NO Cellular Aug 20, 2023 Aug 20, 2023
        • Demethylation of PPAR promotor leading to vascular disrupting effects
        1995 Abnormal lipid metabolism Cellular Apr 7, 2022 Apr 7, 2022
        • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
        560 Abnormal, Foraging activity and behavior Individual Nov 29, 2016 Jun 7, 2018
        • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
        • 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
        • 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
        • Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure
        • Weather event contributes abnormal foraging leading to colony loss/failure
        • Nosema infection increases energetic demands leading to colony loss/failure
        1952 Abnormal, Glucose homeostasis Organ Nov 18, 2021 Nov 18, 2021
        • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
        183 Abnormal, Morphogenesis Nov 29, 2016 Nov 29, 2016
          2094 Abnormal, neuroblast migration Cellular Jan 19, 2023 Jan 19, 2023
          • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
          1891 abnormal, placental labyrinth vasculature morphology Tissue May 31, 2021 May 31, 2021
          • AhR activation leading to preeclampsia
          1108 Abnormal, Role change within caste Population Nov 29, 2016 Jun 7, 2018
          • 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
          • Nosema infection causes abnormal role change that leads to colony loss/failure
          564 Abnormal, Roll change within caste Population 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
          • 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
          535 Abnormal, Sperm penetration (polyspermy) Cellular Nov 29, 2016 Sep 16, 2017
          • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
          • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
          1684 Abnormalities, Cardiac outflow tract formation Organ Aug 13, 2019 Aug 13, 2019
          • TBX1 inhibition leading to congenital cardiac conotruncal anomalies
          1591 Absorption of photon energy Molecular Feb 3, 2019 Feb 5, 2019
            571 Accelerated, Aging Individual Nov 29, 2016 Dec 3, 2016
            • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
            1605 Accumulation of misfolded proteins Cellular Mar 6, 2019 Mar 6, 2019
            • Inhibition of N-linked glycosylation leads to liver injury
            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
            46 Accumulation, Biological membranes Cellular Nov 29, 2016 Sep 16, 2017
            • Narcosis leading to respiratory failure
            68 Accumulation, Collagen Tissue Nov 29, 2016 May 17, 2023
            • Protein Alkylation leading to Liver Fibrosis
            • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
            • Endocytic lysosomal uptake leading to liver fibrosis
            • Binding to ACE2 leading to lung fibrosis
            • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
            • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
            1942 Accumulation, Cytosolic toxic Tau oligomers Cellular 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
            570 Accumulation, Damaged mitochondrial DNA Cellular Nov 29, 2016 Sep 16, 2017
            • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
            327 Accumulation, Fatty acid Organ Nov 29, 2016 Sep 16, 2017
            • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
            • AhR activation leading to hepatic steatosis
            • NR1I3 (CAR) suppression leading to hepatic steatosis
            • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
            • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
            846 Accumulation, Highly carboxylated porphyrins Organ Nov 29, 2016 May 7, 2018
            • Aryl hydrocarbon receptor activation leading to uroporphyria
            291 Accumulation, Triglyceride Cellular Nov 29, 2016 Mar 26, 2024
            • LXR activation leading to hepatic steatosis
            • AhR activation leading to hepatic steatosis
            • Glucocorticoid Receptor activation leading to hepatic steatosis
            • Pregnane X Receptor (PXR) activation leads to liver steatosis
            • Liver X Receptor (LXR) activation leads to liver steatosis
            • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
            1938 ACE2 increased shedding Molecular Oct 17, 2021 Oct 17, 2021
            • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
            1876 ACE2 shedding effects on viral entry Cellular Apr 28, 2021 Apr 28, 2021
              10 Acetylcholine accumulation in synapses Cellular Nov 29, 2016 Jun 26, 2020
              • Acetylcholinesterase inhibition leading to acute mortality
              • Acetylcholinesterase Inhibition Leading to Neurodegeneration
              • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
              • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
              • Various neuronal effects induced by elavl3, sox10, and mbp
              12 Acetylcholinesterase (AchE) Inhibition Cellular Nov 29, 2016 Apr 29, 2020
              • Acetylcholinesterase inhibition leading to acute mortality
              • Acetylcholinesterase Inhibition Leading to Neurodegeneration
              • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
              • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
              • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
              • Various neuronal effects induced by elavl3, sox10, and mbp
              1724 Acinar cell proliferation Cellular Jan 8, 2020 Jan 8, 2020
              • Trypsin inhibition leading to pancreatic acinar cell tumors
              2229 Acrolein accumulation Cellular Jun 3, 2024 Jun 18, 2024
              • CYP450 upregulation leads to Chronic kidney disease
              1340 Activate, calmodulin Molecular Apr 13, 2017 Apr 13, 2017
              • Network of SSRIs (selective serotonin reuptake inhibitors)
              • SSRI (Selective serotonin reuptake inhibitor) to hypertension
              1359 Activate, GABA-A receptor Molecular Apr 14, 2017 Apr 14, 2017
              • Molecular events lead to epilepsy
              1379 Activate, leukocyte Cellular Apr 17, 2017 Apr 17, 2017
              • Gastric ulcer formation
              1380 Activate, mucosal defense Tissue Apr 17, 2017 Apr 17, 2017
              • Gastric ulcer formation
              1383 Activate, phospholipase Molecular Apr 17, 2017 Apr 17, 2017
              • Gastric ulcer formation
              • Helicobacter pylori to gastric ulcer
              1337 Activate, PLC (Phospholipase C) Molecular Apr 13, 2017 Apr 13, 2017
              • Network of SSRIs (selective serotonin reuptake inhibitors)
              • SSRI (Selective serotonin reuptake inhibitor) to hypertension
              1360 Activate, presynaptic neuron 2 Molecular Apr 14, 2017 Apr 14, 2017
              • Molecular events lead to epilepsy
              2173 Activated AKT/ERK/PI3K pathway Cellular Aug 21, 2023 Aug 21, 2023
              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
              2170 Activated ANG/Tie2 pathway Molecular Aug 21, 2023 Aug 21, 2023
              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
              2171 Activated BMP/TGF-beta pathway Cellular Aug 21, 2023 Aug 21, 2023
              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
              2172 Activated Wnt/Frizzled pathway Cellular Aug 21, 2023 Aug 21, 2023
              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
              1385 Activated, gastric ulcer formation Organ Apr 17, 2017 Jun 2, 2017
              • Gastric ulcer formation
              • NSAID induced PTGS1 inactivation to gastric ulcer
              • NSAID induced PTGS2 inactivation to gastric ulcer
              • Helicobacter pylori to gastric ulcer
              1421 Activated, LXR Molecular Jun 2, 2017 Jun 2, 2017
              • NFE2/Nrf2 repression to steatosis
              1355 Activated, membrane depolarization Cellular Apr 14, 2017 Jun 2, 2017
              • Molecular events lead to epilepsy
              • presynaptic neuron 1 activation to epilepsy
              • presynaptic neuron 2 repression to epilepsy
              1351 Activated, NMDA receptor Molecular Apr 14, 2017 Jun 2, 2017
              • Molecular events lead to epilepsy
              • presynaptic neuron 1 activation to epilepsy
              1349 Activated, presynaptic neuron 1 Molecular Apr 14, 2017 Jun 2, 2017
              • Molecular events lead to epilepsy
              • presynaptic neuron 1 activation to epilepsy
              • Various neuronal effects induced by elavl3, sox10, and mbp
              1352 Activated, voltage-gated sodium channel Molecular Apr 14, 2017 Jun 2, 2017
              • Molecular events lead to epilepsy
              • presynaptic neuron 1 activation to epilepsy
              2169 Activation of Angiogenic cytokines Cellular Aug 20, 2023 Aug 20, 2023
              • Demethylation of PPAR promotor leading to vascular disrupting effects
              2168 Activation of angiopoietin like protein 4 Cellular Aug 20, 2023 Aug 20, 2023
              • Demethylation of PPAR promotor leading to vascular disrupting effects
              2038 Activation of calpain signalling Cellular Jul 25, 2022 Jul 25, 2022
              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
              1448 activation of CCAAT/enhancer-binding protein alpha Molecular Jul 24, 2017 Jul 24, 2017
              • Epigenetic modification of PPARG leading to adipogenesis
              1391 Activation of Cyp2E1 Molecular May 30, 2017 Jun 19, 2021
              • Cyp2E1 Activation Leading to Liver Cancer
              • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
              1815 Activation of ER stress Cellular Nov 2, 2020 Nov 2, 2020
              • Immune mediated hepatitis
              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
              1606 Activation of hepatic stellate cells Cellular Mar 6, 2019 Mar 6, 2019
              • Inhibition of N-linked glycosylation leads to liver injury
              2009 Activation of inflammation pathway Cellular May 31, 2022 May 31, 2022
              • Adverse outcome pathway of PM-induced respiratory toxicity
              • Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway
              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
              2036 Activation of metabotropic glutamate receptor Molecular Jul 25, 2022 Jul 25, 2022
              • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
              2146 Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2 Molecular May 25, 2023 Jul 28, 2023
              • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
              • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
              2167 Activation of MMP-2 MMP-9 Cellular Aug 20, 2023 Aug 20, 2023
              • Demethylation of PPAR promotor leading to vascular disrupting effects
              1238 Activation of oxidative stress pathway Molecular Nov 29, 2016 Jun 19, 2017
                2165 Activation of PPAR Cellular Aug 20, 2023 Aug 20, 2023
                • Demethylation of PPAR promotor leading to vascular disrupting effects
                1507 Activation of PPARγ Molecular Mar 18, 2018 Mar 18, 2018
                  1028 Activation of specific nuclear receptors, PPAR-gamma activation Molecular Nov 29, 2016 Sep 16, 2017
                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                  • Epigenetic modification of PPARG leading to adipogenesis
                  288 Activation of specific nuclear receptors, Transcriptional change Cellular Nov 29, 2016 Sep 16, 2017
                  • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                  1271 Activation of TGF-β signaling Cellular Feb 15, 2017 Feb 15, 2017
                  • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                  1974 Activation of Tumor Protein 53 Cellular Mar 9, 2022 Mar 17, 2022
                  • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                  2163 Activation Sema6A Cellular Aug 20, 2023 Aug 20, 2023
                  • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                  1288 Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene Cellular Feb 15, 2017 Sep 16, 2017
                  • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                  1336 Activation, 5-HT2A (Serotonin 2A) Molecular Apr 13, 2017 Apr 13, 2017
                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                  • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                  9 Activation, 5HT2c Molecular Nov 29, 2016 Sep 16, 2017
                  • Kidney toxicity induced by activation of 5HT2C
                  18 Activation, AhR Molecular Nov 29, 2016 Feb 28, 2024
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                  • AhR activation leading to hepatic steatosis
                  • Aryl hydrocarbon receptor activation leading to uroporphyria
                  • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                  • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                  • AhR activation leading to preeclampsia
                  • Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway
                  • Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway
                  • Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
                  • Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway
                  • Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway
                  • Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway
                  • Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway
                  • Activation of the AhR leading to metastatic breast cancer
                  • 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
                  • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                  • AhR activation leading to liver fibrosis
                  • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                  1299 Activation, AKT Molecular Apr 12, 2017 Apr 12, 2017
                  • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                  484 Activation, AKT2 Molecular Nov 29, 2016 Sep 16, 2017
                  • AKT2 activation leading to hepatic steatosis
                  785 Activation, Androgen receptor Molecular Nov 29, 2016 Dec 3, 2016
                  • Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                  • Androgen receptor activation leading to prostate cancer
                  1309 Activation, aPKC Molecular Apr 13, 2017 Apr 13, 2017
                    1038 Activation, beta-2 adrenergic receptor Molecular Nov 29, 2016 Sep 16, 2017
                    • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                    1575 Activation, Caspase 8 pathway Molecular Jan 7, 2019 Mar 7, 2019
                    • IKK complex inhibition leading to liver injury
                    2188 Activation, caspases Cellular Sep 14, 2023 Sep 14, 2023
                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                    66 Activation, ChREBP Molecular Nov 29, 2016 Sep 16, 2017
                    • LXR activation leading to hepatic steatosis
                    • NR1I3 (CAR) suppression leading to hepatic steatosis
                    715 Activation, Constitutive androstane receptor Molecular Nov 29, 2016 Jun 28, 2018
                    • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                    398 Activation, Dendritic Cells Cellular Nov 29, 2016 Dec 3, 2020
                    • Covalent Protein binding leading to Skin Sensitisation
                    • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                    2164 Activation, Dll4-Notch pathway Cellular Aug 20, 2023 Aug 20, 2023
                    • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                    941 Activation, EGFR Molecular Nov 29, 2016 Mar 8, 2023
                    • EGFR Activation Leading to Decreased Lung Function
                    913 Activation, Epidermal Growth Factor Receptor Nov 29, 2016 Nov 29, 2016
                      1181 Activation, Estrogen receptor Molecular Nov 29, 2016 Sep 16, 2017
                      • Estrogen receptor activation leading to breast cancer
                      1065 Activation, estrogen receptor alpha Molecular Nov 29, 2016 Dec 3, 2016
                      • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                      • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                      • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                      116 Activation, FAS Molecular Nov 29, 2016 Sep 16, 2017
                      • LXR activation leading to hepatic steatosis
                      1197 Activation, Fibroblasts Cellular Nov 29, 2016 Sep 16, 2017
                      • Estrogen receptor activation leading to breast cancer
                      • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                      1293 Activation, FOXO Cellular Feb 15, 2017 Sep 16, 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
                      1304 Activation, FXR Molecular Apr 12, 2017 Apr 12, 2017
                        122 Activation, Glucocorticoid Receptor Molecular Nov 29, 2016 Jul 7, 2020
                        • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                        • Glucocorticoid Receptor activation leading to hepatic steatosis
                        • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                        760 Activation, Glutamate-gated chloride channel Molecular Nov 29, 2016 Dec 3, 2016
                        • Glutamate-gated chloride channel activation leading to acute mortality
                        1018 Activation, Glutamate-gated chloride channels Molecular Nov 29, 2016 Sep 16, 2017
                        • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                        • Various neuronal effects induced by elavl3, sox10, and mbp
                        1157 Activation, Hepatic nuclear receptor(s) Molecular Nov 29, 2016 Sep 16, 2017
                        • Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
                        1280 Activation, HIF-1 Cellular Feb 15, 2017 Sep 16, 2017
                        • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                        2162 Activation, HIF1α Cellular Aug 20, 2023 Aug 20, 2023
                        • Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                        1303 Activation, HSD17B4 Molecular Apr 12, 2017 Apr 12, 2017
                          151 Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways Molecular Nov 29, 2016 Nov 5, 2020
                            1297 Activation, insulin receptor Molecular Apr 12, 2017 Apr 12, 2017
                              762 Activation, ionotropic GABA Receptor chloride channel Molecular Nov 29, 2016 Sep 16, 2017
                              • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                              1282 Activation, JAK/STAT pathway Cellular Feb 15, 2017 Sep 16, 2017
                              • Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure
                              1292 Activation, JNK Cellular Feb 15, 2017 Sep 16, 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
                              • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                              1205 Activation, Juvenile hormone receptor Molecular Nov 29, 2016 Sep 16, 2017
                              • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                              826 Activation, Keratinocytes Cellular Nov 29, 2016 Sep 16, 2017
                              • Covalent Protein binding leading to Skin Sensitisation
                              1302 Activation, L-FABP Molecular Apr 12, 2017 Apr 13, 2017
                                1468 Activation, Latent Transforming Growth Factor Beta 1 Molecular Aug 16, 2017 Aug 16, 2017
                                • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                165 Activation, Long term AHR receptor driven direct and indirect gene expression changes Cellular Nov 29, 2016 Dec 2, 2016
                                • Sustained AhR Activation leading to Rodent Liver Tumours
                                1314 Activation, LRH-1 Molecular Apr 13, 2017 Apr 13, 2017
                                  167 Activation, LXR Molecular Nov 29, 2016 May 21, 2024
                                  • LXR activation leading to hepatic steatosis
                                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                                  • Liver X Receptor (LXR) activation leads to liver steatosis
                                  483 Activation, LXR alpha Molecular Nov 29, 2016 Sep 16, 2017
                                  • NFE2L2/FXR activation leading to hepatic steatosis
                                  1198 Activation, Macrophages Cellular Nov 29, 2016 Sep 16, 2017
                                  • Estrogen receptor activation leading to breast cancer
                                  • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                  1998 Activation, Microglia Cellular Apr 7, 2022 Apr 7, 2022
                                  • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                  1300 Activation, mTORC1 Molecular Apr 12, 2017 Apr 12, 2017
                                  • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                  1298 Activation, mTORC2 Molecular Apr 12, 2017 Apr 12, 2017
                                    879 Activation, MTTP Cellular Nov 29, 2016 Sep 16, 2017
                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                    1602 Activation, Muscarinic Acetylcholine Receptors Molecular Feb 6, 2019 Apr 17, 2020
                                    • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                    1174 Activation, NADPH Oxidase Molecular Nov 29, 2016 Sep 16, 2017
                                    • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                    559 Activation, Nicotinic acetylcholine receptor Molecular Nov 29, 2016 Jun 7, 2018
                                    • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                    • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                    • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                    • 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 abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                    • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                    • Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
                                    479 Activation, NR1H4 Molecular Nov 29, 2016 Sep 16, 2017
                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                    478 Activation, NRF2 Molecular Nov 29, 2016 Sep 16, 2017
                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                    2030 Activation, PARP1 Molecular Jul 18, 2022 Jul 18, 2022
                                    • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                    1310 Activation, PI3K Molecular Apr 13, 2017 Apr 13, 2017
                                    • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                    227 Activation, PPARα Molecular Nov 29, 2016 Dec 28, 2020
                                    • PPARα activation in utero leading to impaired fertility in males
                                    • PPARα activation leading to impaired fertility in adult male rodents
                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                    • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                    • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                    • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                    234 Activation, PPARα & PPARγ Molecular Nov 29, 2016 Dec 3, 2016
                                      380 Activation, Pre-MIE: Metabolism of AFB1 Molecular Nov 29, 2016 Nov 29, 2016
                                        239 Activation, Pregnane-X receptor, NR1l2 Molecular Nov 29, 2016 May 22, 2024
                                        • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                        • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                        1369 Activation, PTGS-1 (Prostaglandin-endoperoxide synthase 1) Molecular Apr 17, 2017 Apr 17, 2017
                                        • Gastric ulcer formation
                                        1370 Activation, PTGS-2 (Prostaglandin-endoperoxide synthase 2) Molecular Apr 17, 2017 Apr 17, 2017
                                        • Gastric ulcer formation
                                        245 Activation, PXR/SXR Molecular Nov 29, 2016 Sep 16, 2017
                                        • Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol
                                        • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                        258 Activation, SCD-1 Molecular Nov 29, 2016 Sep 16, 2017
                                        • LXR activation leading to hepatic steatosis
                                        480 Activation, SHP Molecular Nov 29, 2016 Sep 16, 2017
                                        • NFE2L2/FXR activation leading to hepatic steatosis
                                        924 Activation, Sp1 Molecular Nov 29, 2016 Aug 20, 2021
                                          457 Activation, SREBF1 Molecular Nov 29, 2016 Sep 16, 2017
                                          • NR1I3 (CAR) suppression leading to hepatic steatosis
                                          • AKT2 activation leading to hepatic steatosis
                                          1301 Activation, SREBP-1 Molecular Apr 12, 2017 Apr 12, 2017
                                            264 Activation, SREBP-1c Molecular Nov 29, 2016 Sep 16, 2017
                                            • LXR activation leading to hepatic steatosis
                                            265 Activation, Stellate cells Cellular Nov 29, 2016 Nov 10, 2019
                                            • Protein Alkylation leading to Liver Fibrosis
                                            • Endocytic lysosomal uptake leading to liver fibrosis
                                            • AhR activation leading to liver fibrosis
                                            978 Activation, Suppression of NFAT activation and hindrance of nuclear localization Molecular Nov 29, 2016 Dec 3, 2016
                                              1283 Activation, TGF-beta pathway Cellular Feb 15, 2017 Sep 16, 2017
                                              • Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure
                                              • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                              1576 Activation, Tissue resident cells (Kuppfer cells) Cellular Jan 7, 2019 Jan 7, 2019
                                              • IKK complex inhibition leading to liver injury
                                              1469 Activation, Transforming Growth Factor beta pathway Molecular Aug 16, 2017 Aug 16, 2017
                                              • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                              272 Activation/Proliferation, T-cells Organ Nov 29, 2016 Nov 5, 2020
                                              • Covalent Protein binding leading to Skin Sensitisation
                                              • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                              1793 Activator protein 1 activation Cellular Jul 9, 2020 Jul 9, 2020
                                              • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                              1679 Acute inhalation toxicity Individual Jul 3, 2019 Jul 3, 2019
                                                1955 Acute Myeloid Leukemia Individual Dec 3, 2021 Dec 3, 2021
                                                • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                1937 ADAM17 expression induction Cellular Oct 17, 2021 Oct 17, 2021
                                                • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                2177 Adhesion disfunction Cellular Aug 21, 2023 Aug 21, 2023
                                                  2025 Affected folate transporter Cellular Jul 14, 2022 Jul 14, 2022
                                                  • Ceramide synthase inhibition leading to neural tube defects
                                                  25 Agonism, Androgen receptor Molecular Nov 29, 2016 Mar 20, 2017
                                                  • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                  • Androgen receptor agonism leading to male-biased sex ratio
                                                  • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                  111 Agonism, Estrogen receptor Molecular Nov 29, 2016 Sep 16, 2017
                                                  • Estrogen receptor agonism leading to reproductive dysfunction
                                                  • ER agonism leading to skewed sex ratios due to altered sexual differentiation in males
                                                  • ER agonism leading to reduced survival due to renal failure
                                                  1984 Agonism, Estrogen Receptor alpha Molecular Apr 5, 2022 Apr 5, 2022
                                                    2201 Agonism, Retinoic acid receptor Molecular Jan 14, 2024 Jan 24, 2024
                                                    • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                    • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                    1586 Airway epithelial injury Cellular Jan 30, 2019 Jan 30, 2019
                                                    • α-diketone-induced bronchiolitis obliterans
                                                    • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                    2086 Airway inflammation Organ Jan 9, 2023 Jan 17, 2023
                                                    • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                    2013 Airway remodeling Organ May 31, 2022 May 31, 2022
                                                    • Adverse outcome pathway of PM-induced respiratory toxicity
                                                    1907 Airway Surface Liquid Height, Decreased Tissue Jul 19, 2021 Sep 9, 2021
                                                    • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                    97 Alkylation, DNA Molecular Nov 29, 2016 Sep 16, 2017
                                                    • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                    • Alkylation of DNA leading to cancer 1
                                                    • Alkylation of DNA leading to cancer 2
                                                    • Alkylation of DNA leading to reduced sperm count
                                                    244 Alkylation, Protein Molecular Nov 29, 2016 Sep 16, 2017
                                                    • Protein Alkylation leading to Liver Fibrosis
                                                    • Renal protein alkylation leading to kidney toxicity
                                                    1210 Alteration, Food-web structures Population Nov 29, 2016 Dec 3, 2016
                                                    • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                    1060 Alteration, lipid metabolism Cellular Nov 29, 2016 Oct 30, 2023
                                                    • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                    • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                    310 Alteration, Wnt pathway Cellular Nov 29, 2016 Sep 16, 2017
                                                    • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                    854 Alterations, Cellular proliferation / hyperplasia Tissue Nov 29, 2016 Sep 16, 2017
                                                    • Sustained AhR Activation leading to Rodent Liver Tumours
                                                    • Androgen receptor activation leading to prostate cancer
                                                    2089 Altered Bone Cell Homeostasis Cellular Jan 11, 2023 Mar 22, 2023
                                                    • Deposition of energy leading to occurrence of bone loss
                                                    2204 Altered brain morphology Organ Jan 14, 2024 Jan 14, 2024
                                                    • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                    1560 Altered differentiation Cellular Dec 20, 2018 Mar 17, 2022
                                                    • Histone deacetylase inhibition leads to neural tube defects
                                                    2202 Altered expression of cell cycle genes Molecular Jan 14, 2024 Mar 7, 2024
                                                    • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                    • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                    2022 Altered function of the brain Organ Jul 6, 2022 Jul 6, 2022
                                                    • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                    1214 Altered gene expression specific to CAR activation, Hepatocytes Cellular Nov 29, 2016 Dec 19, 2018
                                                    • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                    17 Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway Molecular Nov 29, 2016 Aug 19, 2021
                                                    • Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway
                                                    • Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway
                                                    1921 Altered gene expression, NF-kB dependent Interleukin-6 pathway Molecular Aug 19, 2021 Aug 19, 2021
                                                    • Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway
                                                    • Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
                                                    1917 Altered gene expression, NRF2 dependent antioxidant pathway Molecular Aug 17, 2021 Aug 19, 2021
                                                    • PPARG activation leading to intrahepatic cholestasis
                                                    • Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway
                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                    1923 Altered gene expression, P53 dependent apoptosis pathway Molecular Aug 19, 2021 Aug 19, 2021
                                                    • Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway
                                                    1920 Altered gene expression, TGF-β dependent fibrosis pathway Molecular Aug 19, 2021 Aug 19, 2021
                                                    • Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway
                                                    2221 Altered Liver X receptor activity Molecular Apr 12, 2024 Apr 12, 2024
                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                    2005 Altered neurotransmission in development Cellular May 16, 2022 May 18, 2022
                                                    • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                    2222 Altered peroxisome proliferator–activated receptor alpha activity Molecular Apr 12, 2024 Apr 12, 2024
                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                    21 Altered regulation, Alpha hemoglobin Cellular Nov 29, 2016 Sep 16, 2017
                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                    2066 Altered Signaling Pathways Molecular Sep 28, 2022 Feb 13, 2024
                                                    • Deposition of energy leads to vascular remodeling
                                                    • Deposition of energy leading to occurrence of bone loss
                                                    • Deposition of Energy Leading to Learning and Memory Impairment
                                                    698 Altered, Action Potential Cellular Nov 29, 2016 Mar 31, 2022
                                                    • Altered ion channel activity leading impaired heart function
                                                    1101 Altered, Amphibian metamorphosis Organ Nov 29, 2016 Sep 2, 2020
                                                    • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                    • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                    • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                    • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                    • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                    • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                    • Pendrin inhibition leading to altered amphibian metamorphosis
                                                    • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                    • 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
                                                    1243 Altered, Ca2+-calmodulin activated signal transduction Cellular Nov 29, 2016 Jun 7, 2018
                                                    • 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 abnormal foraging and leads to colony death/failure 1
                                                    • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                    317 Altered, Cardiovascular development/function Organ Nov 29, 2016 Sep 16, 2017
                                                    • 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
                                                    2115 Altered, cholesterol metabolism Molecular Feb 22, 2023 Feb 22, 2023
                                                    • Unknown MIE altering cholesterol metabolism leading to decreased cognition
                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                    723 Altered, Chromosome number Cellular Nov 29, 2016 May 27, 2019
                                                    • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                    536 Altered, Chromosome number (polyploid) zygote Cellular Nov 29, 2016 Sep 16, 2017
                                                    • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                    • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                    1211 Altered, food-web structures Population Nov 29, 2016 Dec 3, 2016
                                                      534 Altered, Formation of cortical envelope Cellular Nov 29, 2016 Sep 16, 2017
                                                      • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                      • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                      1239 Altered, Gene Expression Molecular Nov 29, 2016 Mar 6, 2019
                                                      • Estrogen receptor activation leading to breast cancer
                                                      • Histone deacetylase inhibition leads to neural tube defects
                                                      1930 altered, inner ear development Organ Aug 23, 2021 Aug 24, 2021
                                                      • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                      339 Altered, Larval development Individual Nov 29, 2016 Dec 3, 2016
                                                      • Estrogen receptor agonism leading to reproductive dysfunction
                                                      752 Altered, Meiotic chromosome dynamics Cellular Nov 29, 2016 May 27, 2019
                                                      • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                      • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                      • Deposition of ionising energy leads to population decline via pollen abnormal
                                                      186 Altered, Neuroanatomy Organ Nov 29, 2016 Sep 16, 2017
                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                      192 Altered, Neurophysiology Organ Nov 29, 2016 Sep 16, 2017
                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                      2067 Altered, Nitric Oxide Levels Cellular Sep 28, 2022 Apr 13, 2023
                                                      • Deposition of energy leads to vascular remodeling
                                                      1640 Altered, Photoreceptor patterning Cellular 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
                                                      1240 Altered, Protein Production Cellular Nov 29, 2016 Sep 16, 2017
                                                      • Estrogen receptor activation leading to breast cancer
                                                      363 Altered, Reproductive behaviour Individual Nov 29, 2016 Dec 3, 2016
                                                      • Estrogen receptor agonism leading to reproductive dysfunction
                                                      1877 Altered, retinal layer structure Tissue May 11, 2021 Jul 8, 2022
                                                      • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                      1829 Altered, Thyroid hormone-dependent gene expression Molecular Dec 9, 2020 Dec 9, 2020
                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                      • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                      • AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
                                                      • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                      286 Altered, Transcription of genes by the androgen receptor Tissue Nov 29, 2016 Apr 5, 2024
                                                      • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                      • 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
                                                      • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                      • Androgen receptor activation leading to prostate cancer
                                                      1643 Altered, Visual function Organ May 22, 2019 Jul 8, 2022
                                                      • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                      • 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
                                                      2108 Altered, white brain matter Tissue Feb 21, 2023 Feb 21, 2023
                                                      • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                      • Unknown MIE altering cholesterol metabolism leading to decreased cognition
                                                      • Increased reactive oxygen species production leading to decreased cognitive function
                                                      • Inhibition of voltage-gated sodium channels leading to decreased cognition
                                                      • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                      1673 Alveolar collapse Cellular Jul 3, 2019 Oct 27, 2021
                                                      • Lung surfactant function inhibition leading to decreased lung function
                                                      1674 Alveolar reopening Tissue Jul 3, 2019 Jul 3, 2019
                                                        1428 Analgesia Individual 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
                                                        1127 Anemia, Impaired oxygen and nutrient delivery to tissue, impaired carbon dioxide and waste product removal Nov 29, 2016 Nov 29, 2016
                                                          2160 Angiogenesis disfunction Organ Aug 19, 2023 Aug 19, 2023
                                                            2181 Angiogenesis dysfunction Organ 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
                                                            1935 Angiotensin (1-7) levels diminished Molecular Oct 15, 2021 Oct 15, 2021
                                                            • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                            1936 Angiotensin II degradation reduced Molecular Oct 17, 2021 Oct 17, 2021
                                                            • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                            1688 anogenital distance (AGD), decreased Tissue Aug 30, 2019 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
                                                            • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                            1685 Anomalies, Congenital cardiac conotruncal Individual Aug 13, 2019 Aug 13, 2019
                                                            • TBX1 inhibition leading to congenital cardiac conotruncal anomalies
                                                            1073 anovulation, Nov 29, 2016 Nov 29, 2016
                                                              26 Antagonism, Androgen receptor Molecular Nov 29, 2016 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 decreased fertility in females
                                                              • Androgen receptor antagonism leading to testicular cancer
                                                              • Androgen receptor (AR) antagonism leading to hypospadias in male offspring
                                                              • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                              112 Antagonism, Estrogen receptor Molecular Nov 29, 2016 Sep 16, 2017
                                                              • Estrogen receptor antagonism leading to reproductive dysfunction
                                                              • DNA damage and mutations leading to Metastatic Breast Cancer
                                                              • Estrogen antagonism leading to increased risk of autism-like behavior
                                                              2220 Antagonism, Glucocorticoid hormone receptor Molecular Apr 12, 2024 Apr 12, 2024
                                                              • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                              638 Antagonism, Histamine Receptor (H2) Molecular Nov 29, 2016 Sep 16, 2017
                                                              • Histamine (H2) receptor antagonism leading to reduced survival
                                                              2027 Antagonism, Smoothened receptor Molecular Jul 15, 2022 Jul 28, 2022
                                                              • Antagonism of Smoothened receptor leading to orofacial clefting
                                                              1656 Antagonism, Thyroid Receptor Molecular Jun 8, 2019 Jan 11, 2021
                                                              • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                              • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                              • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                              1691 Antagonism,LH receptor Molecular Oct 3, 2019 Oct 3, 2019
                                                              • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                              1432 Anti-depressant Activity Individual 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
                                                              1169 Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin Molecular Nov 29, 2016 Dec 3, 2016
                                                              • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                              1148 Anticoagulant rodenticide interferes with gamma-carboxyglutamate formation, Inhibition of protein synthesis in bone Nov 29, 2016 Nov 29, 2016
                                                                1262 Apoptosis Cellular Feb 7, 2017 Feb 28, 2024
                                                                • AOP from chemical insult to cell death
                                                                • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                • Histone deacetylase inhibition leading to testicular atrophy
                                                                • Inhibition of N-linked glycosylation leads to liver injury
                                                                • Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway
                                                                • Activation of the AhR leading to metastatic breast cancer
                                                                • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                • AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
                                                                • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                525 Apoptosis of adult Leydig cells, Decreased testosterone by adult Leydig cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                • Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
                                                                2184 Apoptosis of vascular smooth muscle cells Cellular Sep 4, 2023 Sep 4, 2023
                                                                  1817 Apoptotic cell death Cellular Nov 2, 2020 Nov 2, 2020
                                                                  • Immune mediated hepatitis
                                                                  • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                                                  1443 Atherosclerosis Individual Jun 29, 2017 Dec 18, 2023
                                                                  • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                  2209 autism-like behavior Individual Jan 25, 2024 Jan 25, 2024
                                                                  • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                  1814 benzoquinone imine and acylglucuronide metabolites Molecular Nov 2, 2020 Nov 2, 2020
                                                                  • Immune mediated hepatitis
                                                                  1755 beta-catenin activation Cellular Mar 23, 2020 Nov 25, 2022
                                                                  • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                  214 Bile accumulation, Pathological condition Cellular Nov 29, 2016 Sep 16, 2017
                                                                  • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                  857 Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain Molecular Nov 29, 2016 Nov 29, 2016
                                                                    667 Binding at picrotoxin site, iGABAR chloride channel Molecular Nov 29, 2016 Apr 29, 2019
                                                                    • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                    2218 Binding of (ant)agonist to liver X receptor Molecular Apr 12, 2024 Apr 12, 2024
                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                    2219 Binding of (ant)agonist to peroxisome proliferator–activated receptor alpha Molecular Apr 12, 2024 Apr 12, 2024
                                                                    • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                    1851 Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) Molecular Mar 30, 2021 Mar 30, 2021
                                                                    • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                    • Binding to ACE2 leading to lung fibrosis
                                                                    875 Binding of agonist, Ionotropic glutamate receptors Molecular Nov 29, 2016 Sep 16, 2017
                                                                    • 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
                                                                    387 Binding of agonist, NMDARs Molecular Nov 29, 2016 Nov 29, 2016
                                                                      2217 Binding of antagonist to glucocorticoid hormone receptor Molecular Apr 12, 2024 Apr 12, 2024
                                                                      • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                      2216 Binding of antagonist to thyroid hormone receptor Molecular Apr 12, 2024 Apr 12, 2024
                                                                      • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                      201 Binding of antagonist, NMDA receptors Molecular 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
                                                                      998 Binding of antagonist, PPAR alpha Molecular Nov 29, 2016 Sep 16, 2017
                                                                      • Antagonist binding to PPARα leading to body-weight loss
                                                                      2234 Binding of C6R-Derived Protein K7 Molecular Jun 10, 2024 Jun 19, 2024
                                                                      • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                      1199 Binding of FK506 to FKBP12, Nov 29, 2016 Nov 29, 2016
                                                                        1200 Binding of FK506 to FKBP12, Formation Nov 29, 2016 Nov 29, 2016
                                                                          1653 Binding of inhibitor to mitochondrial complex III Molecular Jun 7, 2019 Jun 7, 2019
                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                          1654 Binding of inhibitor to mitochondrial complex IV Molecular Jun 7, 2019 Jun 7, 2019
                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                          1655 Binding of inhibitor to mitochondrial complex V Molecular Jun 7, 2019 Jun 7, 2019
                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                          888 Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) Molecular Nov 29, 2016 Mar 28, 2018
                                                                          • 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
                                                                          1580 Binding of microtubule stabilizing agents (MSA) to microtubules Molecular Jan 29, 2019 Jan 29, 2019
                                                                          • Microtubule interacting drugs lead to peripheral neuropathy
                                                                          1486 Binding of substrate, endocytic receptor Molecular Oct 25, 2017 Oct 25, 2017
                                                                          • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                          1485 Binding of substrate, endocytotic receptor Molecular Oct 25, 2017 Oct 25, 2017
                                                                            1252 Binding to (interferes with) topoisomerase II enzyme Molecular Dec 16, 2016 Aug 1, 2022
                                                                            • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                            1739 Binding to ACE2 Molecular Mar 2, 2020 Aug 30, 2023
                                                                            • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                            • 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
                                                                            • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                            • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                            • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                            • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
                                                                            • SARS-CoV-2 infection leading to hyperinflammation
                                                                            • SARS-CoV-2 infection leading to pyroptosis
                                                                            • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                            • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                                            • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                            • Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
                                                                            • 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)
                                                                            1710 Binding to estrogen receptor (ER)-α in immune cells Molecular Dec 29, 2019 Aug 14, 2020
                                                                            • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                            1956 Binding to hERG channel Molecular Dec 13, 2021 Dec 13, 2021
                                                                              1353 Binding to voltage-gated sodium channel Molecular Apr 14, 2017 Nov 10, 2023
                                                                              • Molecular events lead to epilepsy
                                                                              • presynaptic neuron 1 activation to epilepsy
                                                                              • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                              • Inhibition of voltage-gated sodium channels leading to decreased cognition
                                                                              977 Binding, Binding of calcineurin with FK506-FKBP complexes Nov 29, 2016 Nov 29, 2016
                                                                                2109 Binding, extracellular matrix protein laminin Molecular Feb 21, 2023 Feb 21, 2023
                                                                                • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                1201 Binding, Immunophilins Molecular Nov 29, 2016 Oct 17, 2017
                                                                                  261 Binding, SH-/selen-proteins Molecular Nov 29, 2016 Sep 16, 2017
                                                                                    1487 Binding, Thiol/seleno-proteins involved in protection against oxidative stress Molecular Nov 9, 2017 Jul 15, 2022
                                                                                    • 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 electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                    1831 Binding, Thyroid binding globulin in serum Molecular Dec 9, 2020 Dec 9, 2020
                                                                                    • Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
                                                                                    957 Binding, Transthyretin in serum Molecular Nov 29, 2016 Sep 16, 2017
                                                                                    • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                    • Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
                                                                                    718 Binding, Tubulin Molecular Nov 29, 2016 Apr 20, 2021
                                                                                    • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                    301 Binding, VEGF-A Nov 29, 2016 Nov 29, 2016
                                                                                      1716 Blockade of STAT5 phosphorylation Cellular Jan 5, 2020 Feb 15, 2021
                                                                                      • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                      1529 Blockade, L-Type Calcium Channels Molecular Jun 19, 2018 Nov 1, 2018
                                                                                      • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                      1570 Blocking of IL-1R Molecular Dec 24, 2018 Jun 1, 2019
                                                                                        1874 blood brain barrier disruption Cellular Apr 27, 2021 Apr 27, 2021
                                                                                        • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
                                                                                        1676 Blood extravasation into the lungs Organ Jul 3, 2019 Jul 3, 2019
                                                                                          1132 Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal Cellular Nov 29, 2016 Dec 3, 2016
                                                                                          • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                          1867 Bradykinin system, hyperactivated Molecular Apr 20, 2021 Jan 24, 2022
                                                                                          • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                          2093 Brain thyroid hormone (T4/T3) decreased Organ Jan 19, 2023 Jan 19, 2023
                                                                                          • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                                                          1588 Bronchiolitis obliterans Individual Jan 30, 2019 Jan 30, 2019
                                                                                          • α-diketone-induced bronchiolitis obliterans
                                                                                          1879 Bulky DNA adducts, increase Molecular May 17, 2021 May 17, 2021
                                                                                          • Bulky DNA adducts leading to mutations
                                                                                          1149 Calcium cannot bind to the hydroxyapatite matrix of bone, Osteocalcin and other bone proteins (periostin, MGP and periostin like factor) not formed Nov 29, 2016 Nov 29, 2016
                                                                                            2236 Cardiac Heart Failure Organ Jun 10, 2024 Jun 10, 2024
                                                                                            • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                            2001 Cardiac hypertrophy Organ Apr 22, 2022 Apr 22, 2022
                                                                                              2190 Cardiomyocyte differentiation inhibition Cellular Sep 16, 2023 Sep 16, 2023
                                                                                                1505 Cell cycle, disrupted Cellular Jan 21, 2018 Jun 30, 2021
                                                                                                • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                • AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
                                                                                                • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                55 Cell injury/death Cellular Nov 29, 2016 Jul 15, 2022
                                                                                                • 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 induces impairment of learning and memory abilities
                                                                                                • Protein Alkylation leading to Liver Fibrosis
                                                                                                • 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
                                                                                                • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                • 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
                                                                                                • IKK complex inhibition leading to liver injury
                                                                                                • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                • Mitochondrial complex inhibition leading to liver injury
                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                • 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
                                                                                                • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                • AhR activation leading to liver fibrosis
                                                                                                • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                2103 Cellular dysfunction (human placenta trophoblast cells) Cellular Feb 7, 2023 Feb 7, 2023
                                                                                                  429 Cellular Proliferation and Clonal Expansion of Mutant Cells (Pre-neoplastic Foci), Alteration of cellular growth homeostasis Nov 29, 2016 Nov 29, 2016
                                                                                                    1875 Cerebrovascular disease (stroke) Organ Apr 27, 2021 Mar 30, 2022
                                                                                                    • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
                                                                                                    853 Changes/Inhibition, Cellular Homeostasis and Apoptosis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                    • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                    1564 Chemical induced Fanconi syndrome Individual Dec 20, 2018 Dec 20, 2018
                                                                                                    • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                    357 Cholestasis, Pathology Individual Nov 29, 2016 Dec 3, 2016
                                                                                                    • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                    1454 chronic high fat diet Individual Jul 24, 2017 Jul 24, 2017
                                                                                                    • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                    1603 Chronic kidney disease Organ Feb 18, 2019 Jun 16, 2024
                                                                                                    • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                                    • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                    • CYP450 upregulation leads to Chronic kidney disease
                                                                                                    1894 chronic low grade systemic inflammation Individual Jun 24, 2021 Jun 24, 2021
                                                                                                      2008 Chronic obstructive pulmonary disease Individual May 31, 2022 May 31, 2022
                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                      1753 Chronic reactive oxygen species Molecular Mar 23, 2020 Nov 9, 2021
                                                                                                      • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                      1251 Chronic, Mucus hypersecretion Tissue Nov 29, 2016 Aug 25, 2021
                                                                                                        1908 Cilia Beat Frequency, Decreased Cellular Jul 19, 2021 Sep 10, 2021
                                                                                                        • 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
                                                                                                        491 Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Organ Nov 29, 2016 Sep 16, 2017
                                                                                                        • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                        1845 Coagulation Organ Mar 25, 2021 Aug 30, 2023
                                                                                                        • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                        402 Cognitive Function, Decreased Individual Nov 29, 2016 Aug 9, 2018
                                                                                                        • 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
                                                                                                        • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                        • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                        • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                        • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                                                                        • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                                        • Unknown MIE altering cholesterol metabolism leading to decreased cognition
                                                                                                        • Increased reactive oxygen species production leading to decreased cognitive function
                                                                                                        • Inhibition of voltage-gated sodium channels leading to decreased cognition
                                                                                                        • 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
                                                                                                        2075 Cognitive, sensed as hypoxic/low oxygen environment Organ Nov 16, 2022 Nov 16, 2022
                                                                                                        • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                        1275 Collagen Deposition Tissue Feb 15, 2017 Feb 15, 2017
                                                                                                        • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                        1558 Collagen production, reduced Tissue Dec 20, 2018 Dec 20, 2018
                                                                                                        • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                        1997 Colon epithelial injury Organ Apr 7, 2022 Apr 7, 2022
                                                                                                          2101 Conformational changes of thyroid receptor Molecular Feb 7, 2023 Feb 7, 2023
                                                                                                            2131 Conjugation, GSH Cellular Apr 5, 2023 Sep 14, 2023
                                                                                                            • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                            1832 Coordinated gene expression changes by PPARα activation Molecular Dec 19, 2020 Dec 19, 2020
                                                                                                              1835 Cortisol and 11β-(OH) testosterone decreased Cellular Feb 9, 2021 Feb 9, 2021
                                                                                                              • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                              1221 Cough, Dyspnea, Sneezing, Acute respiratory effect Nov 29, 2016 Nov 29, 2016
                                                                                                                396 Covalent Binding, Protein Molecular Nov 29, 2016 Nov 5, 2020
                                                                                                                • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                1508 CYP2E1 Activation Molecular Mar 26, 2018 Apr 9, 2018
                                                                                                                • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                2228 CYP450 Upregulation Molecular Jun 3, 2024 Jun 11, 2024
                                                                                                                • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                1386 CYP7B activity, inhibition Molecular 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
                                                                                                                1906 Cystic Fibrosis Transmembrane Regulator Function, Decreased Molecular Jul 19, 2021 Aug 3, 2021
                                                                                                                • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                2102 Cytotoxicity (human trophoblast cells) Cellular Feb 7, 2023 Feb 7, 2023
                                                                                                                  829 Damage, Lipid bilayer Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                  • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                  250 Damaging, Red blood cells; hemolysis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                  • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                  563 Death/Failure, Colony Population Nov 29, 2016 Jun 7, 2018
                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                  • Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure
                                                                                                                  • 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
                                                                                                                  • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                  • 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 abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                  • Increased metabolic stress contributes to abnormal foraging 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
                                                                                                                  2200 decline, neural progenitor cells Organ Jan 10, 2024 Jan 10, 2024
                                                                                                                  • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                  361 Decline, Population Population Nov 29, 2016 Dec 3, 2016
                                                                                                                  • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                  679 Decline, Population trajectory Population Nov 29, 2016 Dec 3, 2016
                                                                                                                  • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                  1258 Decompartmentalization Cellular Feb 7, 2017 Sep 16, 2017
                                                                                                                  • AOP from chemical insult to cell death
                                                                                                                  1890 Decrease (loss of) fetal male germ cells Cellular May 29, 2021 Nov 11, 2021
                                                                                                                  • Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
                                                                                                                  1545 Decrease in mitochondrial oxidative phosphorylation Cellular Dec 19, 2018 Dec 19, 2018
                                                                                                                  • Mitochondrial complex inhibition leading to liver injury
                                                                                                                  2215 Decrease Left Ventricular function Organ Apr 3, 2024 Apr 3, 2024
                                                                                                                  • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                  • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                  1696 Decrease of egg production and cummulative fecundity Individual Oct 3, 2019 Oct 3, 2019
                                                                                                                  • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                  851 Decrease of GABAergic interneurons Cellular Nov 29, 2016 Apr 4, 2019
                                                                                                                  • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                  386 Decrease of neuronal network function Organ Nov 29, 2016 May 28, 2018
                                                                                                                  • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                  • Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                  • 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
                                                                                                                  • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                                  • 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
                                                                                                                  • Excessive iron accumulation leading to neurological disorders
                                                                                                                  • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                  • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                  385 Decrease of synaptogenesis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                  • 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
                                                                                                                  425 Decrease of Thyroidal iodide Cellular Nov 29, 2016 Apr 4, 2019
                                                                                                                  • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                  • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                  • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                  • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                  2057 Decrease, hatching of egg Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                  • Doda decarboxylase leading to mortality
                                                                                                                  2058 Decrease, 20-hydroxyecdysone Molecular Aug 28, 2022 Aug 28, 2022
                                                                                                                  • Knickkopf leading to mortality
                                                                                                                  993 Decrease, Abdominal muscle contraction Tissue Nov 29, 2016 May 24, 2018
                                                                                                                  • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                  1834 Decrease, Acyl-CoA dehydrogenases Molecular Jan 15, 2021 Jan 15, 2021
                                                                                                                  • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                  1771 Decrease, Adenosine triphosphate pool Cellular Apr 30, 2020 Jun 14, 2021
                                                                                                                  • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                  • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
                                                                                                                  • Thermal stress leading to population decline (1)
                                                                                                                  • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                  • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                  • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                  • Mitochondrial complex III antagonism leading to growth inhibition (2)
                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                  1614 Decrease, androgen receptor activation Tissue Apr 10, 2019 Apr 5, 2024
                                                                                                                  • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                  • 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
                                                                                                                  • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                  • Androgen receptor antagonism leading to testicular cancer
                                                                                                                  • Androgen receptor (AR) antagonism leading to hypospadias in male offspring
                                                                                                                  • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                  914 Decrease, Apoptosis of ciliated epithelial cells Cellular Nov 29, 2016 Aug 17, 2021
                                                                                                                    35 Decrease, Aromatase (Cyp19a1) Cellular Nov 29, 2016 Nov 29, 2016
                                                                                                                      1966 Decrease, Asexual reproduction Individual Jan 17, 2022 Jan 17, 2022
                                                                                                                        1472 Decrease, ATP production Cellular Oct 10, 2017 Apr 11, 2021
                                                                                                                        • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                        • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                        • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                        1808 Decrease, ATP synthase activity Molecular Nov 2, 2020 Nov 2, 2020
                                                                                                                          792 Decrease, Bioactivation of testosterone Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                            1534 Decrease, Blood pressure Individual Jun 19, 2018 Jun 19, 2018
                                                                                                                              1531 Decrease, Calcium binding to Troponin C Cellular Jun 19, 2018 Jun 19, 2018
                                                                                                                              • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                              1530 Decrease, Calcium currents Cellular Jun 19, 2018 Jun 19, 2018
                                                                                                                              • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                              1532 Decrease, Cardiac contractility Organ Jun 19, 2018 Jun 19, 2018
                                                                                                                              • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                              • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                              • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                              1533 Decrease, Cardiac ejection fraction Organ Jun 19, 2018 Jun 19, 2018
                                                                                                                              • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                              1821 Decrease, Cell proliferation Cellular 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)
                                                                                                                              • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                              • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                              • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                              • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                              • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                                                                              2060 Decrease, Chitin laminar organization Tissue Aug 28, 2022 Aug 28, 2022
                                                                                                                              • Knickkopf leading to mortality
                                                                                                                              1473 Decrease, Chlorophyll synthesis Cellular Oct 10, 2017 Oct 10, 2017
                                                                                                                              • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                              1266 Decrease, Circulating crustacean cardioactive peptide Tissue Feb 9, 2017 May 24, 2018
                                                                                                                              • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                              988 Decrease, Circulating ecdysis triggering hormone Tissue Nov 29, 2016 May 24, 2018
                                                                                                                              • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                              1446 Decrease, Coupling of oxidative phosphorylation Molecular Jun 29, 2017 May 28, 2021
                                                                                                                              • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                              • 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 increased cytosolic calcium
                                                                                                                              • 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
                                                                                                                              1523 Decrease, Cuticular chitin content Tissue 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
                                                                                                                              1313 Decrease, cytosolic fatty acid Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                996 Decrease, Digestion of old cuticle Organ Nov 29, 2016 Oct 21, 2020
                                                                                                                                • Chitinase inhibition leading to mortality
                                                                                                                                • Chitobiase inhibition leading to mortality
                                                                                                                                1613 Decrease, dihydrotestosterone (DHT) level Tissue Apr 10, 2019 Apr 5, 2024
                                                                                                                                • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                • 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                2052 Decrease, dopa decarboxylase Cellular Aug 28, 2022 Aug 28, 2022
                                                                                                                                • Doda decarboxylase leading to mortality
                                                                                                                                1056 Decrease, E2 blood concentrations at hypothalamus Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                1267 Decrease, Ecdysis motoneuron bursts Tissue Feb 9, 2017 May 24, 2018
                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                2196 Decrease, elavl3 Molecular Oct 17, 2023 Oct 17, 2023
                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                1268 Decrease, Excitatory postsynaptic potential Tissue Feb 9, 2017 May 24, 2018
                                                                                                                                • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                1699 Decrease, expression of gonadotropin releasing hormone receptor Molecular Oct 30, 2019 Oct 30, 2019
                                                                                                                                • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                1824 Decrease, Fatty acid β-oxidation Cellular Nov 25, 2020 Nov 25, 2020
                                                                                                                                  328 Decrease, Fecundity Individual Nov 29, 2016 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)
                                                                                                                                  • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                  • 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
                                                                                                                                  1781 Decrease, Fecundity (F3) Individual Apr 30, 2020 Apr 30, 2020
                                                                                                                                  • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                  • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                  330 Decrease, Fertility Individual Nov 29, 2016 Jun 29, 2017
                                                                                                                                  • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                  2040 Decrease, GLI1/2 target gene expression Cellular Jul 25, 2022 Mar 22, 2023
                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                  • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                  • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                                                                                  2028 Decrease, GLI1/2 translocation to nucleus Molecular Jul 15, 2022 Oct 28, 2022
                                                                                                                                  • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                  • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                                                                                  1773 Decrease, Global DNA methylation Molecular 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)
                                                                                                                                  2071 Decrease, Glucose pool Cellular Nov 1, 2022 Nov 1, 2022
                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                  1951 Decrease, Glucose uptake Cellular Nov 18, 2021 Nov 18, 2021
                                                                                                                                  • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                  1949 Decrease, GLUT4 Cellular Nov 18, 2021 Nov 18, 2021
                                                                                                                                  • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                  1476 Decrease, Glycolysis Cellular Oct 10, 2017 Oct 10, 2017
                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                  1521 Decrease, Growth Individual May 24, 2018 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 ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                  • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                  • Mitochondrial complex III antagonism leading to growth inhibition (2)
                                                                                                                                  • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                  • 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 glucose depletion
                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                  • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                  1778 Decrease, Heritable DNA methylation (F3) Molecular Apr 30, 2020 Apr 30, 2020
                                                                                                                                  • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                  • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                  633 Decrease, histaminergic neuron excitation Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                  • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                  788 Decrease, Incorporation of active iodide into iodotyrosines Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                    867 Decrease, Intracellular pH Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                    • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                    2059 Decrease, knickkopf gene Cellular Aug 28, 2022 Aug 28, 2022
                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                    1478 Decrease, Leaf cell mitosis Tissue Oct 10, 2017 Oct 10, 2017
                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                    1479 Decrease, Leaf development Organ Oct 10, 2017 Oct 10, 2017
                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                    • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                    1377 Decrease, leukocyte adherence Tissue Apr 17, 2017 Apr 17, 2017
                                                                                                                                    • Gastric ulcer formation
                                                                                                                                    1474 Decrease, Light harvest capacity Cellular Oct 10, 2017 Oct 10, 2017
                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                    1250 Decrease, Lung function Individual Nov 29, 2016 Sep 8, 2021
                                                                                                                                    • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                    • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                    • Oxidative stress Leading to Decreased Lung Function
                                                                                                                                    • Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway
                                                                                                                                    • Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway
                                                                                                                                    • Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
                                                                                                                                    • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                    2198 Decrease, mbp Molecular Oct 17, 2023 Oct 17, 2023
                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                    40 Decrease, Mitochondrial ATP production Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                    • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                    • Renal protein alkylation leading to kidney toxicity
                                                                                                                                    • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                    • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                    1770 Decrease, Mitochondrial membrane potential Cellular 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
                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                    1772 Decrease, Neutral lipids Tissue Apr 30, 2020 Apr 30, 2020
                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                    2063 Decrease, New cuticle secretion Organ Aug 28, 2022 Aug 28, 2022
                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                    572 Decrease, Number of worker bees Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                    • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                    • 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
                                                                                                                                    • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                    1366 Decrease, Oogenesis Organ Apr 15, 2017 Apr 30, 2020
                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                    • Thermal stress leading to population decline (3)
                                                                                                                                    • Thermal stress leading to population decline (2)
                                                                                                                                    • Thermal stress leading to population decline (1)
                                                                                                                                    • 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
                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                    1782 Decrease, Oogenesis (F3) Organ Apr 30, 2020 Apr 30, 2020
                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                    • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                    488 Decrease, Ovulation Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                    1477 Decrease, Oxidative phosphorylation Cellular Oct 10, 2017 Dec 20, 2018
                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                    • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                    • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                    2041 Decrease, palatal shelf outgrowth Tissue Jul 27, 2022 May 16, 2023
                                                                                                                                    • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                    • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                    • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                                                                                    1475 Decrease, Photosynthesis Cellular Oct 10, 2017 Oct 10, 2017
                                                                                                                                    • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                    • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                    • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                    1517 Decrease, Photosystem II activity Molecular May 24, 2018 Oct 7, 2020
                                                                                                                                      1862 Decrease, Photosystem II efficiency Cellular 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
                                                                                                                                      1810 Decrease, Plasma membrane ATPase activity Cellular Nov 2, 2020 Nov 2, 2020
                                                                                                                                        360 Decrease, Population growth rate Population Nov 29, 2016 Jan 3, 2023
                                                                                                                                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                        • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                        • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                        • Estrogen receptor antagonism leading to reproductive dysfunction
                                                                                                                                        • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                        • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                        • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                        • 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
                                                                                                                                        • 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
                                                                                                                                        • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                        • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                        • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                        • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                        • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                        • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                        • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                        • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                        • Inhibition of 5α-reductase leading to impaired fecundity in female fish
                                                                                                                                        • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                        • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                        • Thermal stress leading to population decline (3)
                                                                                                                                        • Thermal stress leading to population decline (2)
                                                                                                                                        • Thermal stress leading to population decline (1)
                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
                                                                                                                                        • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                        • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                        • Androgen receptor agonism leading to male-biased sex ratio
                                                                                                                                        • 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
                                                                                                                                        • 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
                                                                                                                                        • 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
                                                                                                                                        • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                        • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                        • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                        • 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
                                                                                                                                        • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                        2061 Decrease, Prevent chitin degradation by chitinases Tissue Aug 28, 2022 Aug 28, 2022
                                                                                                                                        • Knickkopf leading to mortality
                                                                                                                                        1863 Decrease, Reproduction Individual 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
                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                        • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                        • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                        • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                        771 Decrease, Serum thyroid hormone (T4/T3) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                        • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                                                                                                        2044 Decrease, Smoothend relocation and activation Cellular Aug 23, 2022 Oct 27, 2022
                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                        2043 Decrease, Sonic Hedgehog second messenger production Cellular Aug 12, 2022 Mar 22, 2023
                                                                                                                                        • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                        • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                        • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                                                                                        2197 Decrease, sox10 Molecular Oct 17, 2023 Oct 17, 2023
                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                        2020 Decrease, sox9 expression Molecular Jun 28, 2022 Aug 11, 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
                                                                                                                                        266 Decrease, Steroidogenic acute regulatory protein (STAR) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                        • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                        1382 Decrease, surfactant Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                        • Gastric ulcer formation
                                                                                                                                        • Helicobacter pylori to gastric ulcer
                                                                                                                                        1690 Decrease, testosterone levels Tissue Aug 30, 2019 May 24, 2024
                                                                                                                                        • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                        • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                        • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                        • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                        • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                        • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                        • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                        • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                        1612 Decrease, testosterone synthesis/level Cellular Apr 10, 2019 Apr 10, 2019
                                                                                                                                          1687 decrease, transcription of genes by AR Cellular Aug 30, 2019 Aug 30, 2019
                                                                                                                                          • Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                          • Androgen receptor antagonism leading to testicular cancer
                                                                                                                                          1622 Decrease, Transgenerational DNA methylation Molecular Apr 22, 2019 Apr 22, 2019
                                                                                                                                            289 Decrease, Translocator protein (TSPO) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                            • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                            2051 Decrease, Tyrosine Molecular Aug 28, 2022 Aug 28, 2022
                                                                                                                                            • Doda decarboxylase leading to mortality
                                                                                                                                            642 Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                            • Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
                                                                                                                                            646 Decreased Cholesterol, Decreased sperm quantity and/or quality in the adult testis Organ Nov 29, 2016 Dec 3, 2016
                                                                                                                                            • Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
                                                                                                                                            645 Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                            • Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
                                                                                                                                            644 Decreased Cholesterol, Decreased Transport of Cholesterol to the Inner Mitochondrial Membrane Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                            • Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
                                                                                                                                            643 Decreased Cholesterol, Decreased Uptake of Lipoproteins Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                            • Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
                                                                                                                                            1452 decreased DNA methylation of tyrosine hydroxylase Cellular Jul 24, 2017 Jul 24, 2017
                                                                                                                                            • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                            1450 decreased dopamine Molecular Jul 24, 2017 Jul 24, 2017
                                                                                                                                            • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                            2176 Decreased endothelial cell proliferation Cellular Aug 21, 2023 Aug 21, 2023
                                                                                                                                              543 Decreased fertility in the adult, Decreased sperm quantity and/or quality in the adult testis Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                              • Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
                                                                                                                                              972 Decreased fertility, Reduced number of oocytes ovulated Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                              • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                              2026 decreased folate uptake Cellular Jul 14, 2022 Jul 14, 2022
                                                                                                                                              • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                              969 Decreased GnRH Release, Decreased Kisspeptin stimulation of GnRH neurons Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                              • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                              1571 Decreased IL-1 production Cellular Dec 24, 2018 Jun 24, 2019
                                                                                                                                                968 Decreased Kisspeptin release from neurons in AVPV, Decreased hypothalamic estrogen reduces kisspeptinergic neuron response Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                970 Decreased LH release from Anterior Pituitary, Decreased GnRH stimulation of Anterior Pituitary Gonadotrophs Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                1453 decreased methylation of dopamine transporter promoter Cellular Jul 24, 2017 Jul 24, 2017
                                                                                                                                                • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                1751 Decreased mortality Individual Mar 17, 2020 Mar 17, 2020
                                                                                                                                                  1562 Decreased Na/K ATPase activity Cellular Dec 20, 2018 Dec 20, 2018
                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                  • Na+ /K+ -ATPase inhibition leading to hypertension
                                                                                                                                                  1837 decreased oocyte maturation Organ Feb 9, 2021 Feb 9, 2021
                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                  1836 Decreased plasma Cortisol level Tissue Feb 9, 2021 Feb 9, 2021
                                                                                                                                                  • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                  1642 Decreased plasma RA level Tissue May 22, 2019 May 22, 2019
                                                                                                                                                  • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                  967 Decreased positive estrogenic feedback on hypothalamus, Reduced estradiol in circulation decreases estrogen concentration at hypothalamus Organ Nov 29, 2016 Dec 3, 2016
                                                                                                                                                  • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                  2203 Decreased proliferation of cortical neural progenitor cells Cellular Jan 14, 2024 Jan 29, 2024
                                                                                                                                                  • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                  • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                  1538 Decreased protection against oxidative stress Cellular Sep 13, 2018 Jul 15, 2022
                                                                                                                                                  • 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 electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                                                                                  1563 Decreased proximal tubular vectorial transport Tissue Dec 20, 2018 Dec 20, 2018
                                                                                                                                                  • Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
                                                                                                                                                  1641 Decreased retinoic acid (RA) synthesis Cellular May 22, 2019 May 22, 2019
                                                                                                                                                  • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                  1451 decreased reward Individual Jul 24, 2017 Jul 24, 2017
                                                                                                                                                  • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                  1981 Decreased SIRT1 expression Cellular Mar 22, 2022 Mar 24, 2022
                                                                                                                                                  • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                  2140 Decreased spawning and cumulative fecundity, decreased gonadosomatic index Individual May 16, 2023 May 16, 2023
                                                                                                                                                    505 Decreased sperm quantity / quality in the adult, Decreased fertility Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
                                                                                                                                                    520 Decreased sperm quantity or quality in the adult, Decreased fertility Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
                                                                                                                                                    • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                    • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                    1798 Decreased spermatogenesis Organ Jul 13, 2020 Feb 9, 2021
                                                                                                                                                    • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                    • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                    649 Decreased steroidogenesis, Alterations in the Leydig Cell Cytoskeleton Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
                                                                                                                                                    647 Decreased steroidogenesis, Decreased Activity of Steroidogenic Enzymes in Adult Leydig cells Cellular Nov 29, 2016 Apr 16, 2024
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
                                                                                                                                                    • 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
                                                                                                                                                    648 Decreased steroidogenesis, Increased Apoptosis of Adult Leydig Cells Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
                                                                                                                                                    640 Decreased steroidogenesis, Proteomic alterations in the adult Leydig cell Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
                                                                                                                                                    660 decreased testosterone by fetal Leydig cells, Dysgenesis of fetal Leydig cells Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
                                                                                                                                                    659 Decreased testosterone by the fetal Leydig cells, Activation by other estradiol agonists Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
                                                                                                                                                    654 Decreased testosterone by the fetal Leydig cells, Activation by other glucocorticoid receptor agonists Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
                                                                                                                                                    661 Decreased testosterone by the fetal Leydig cells, Alterations in the fetal testis proteome Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
                                                                                                                                                    541 Decreased testosterone by the fetal Leydig cells, Decreased COUP-TFII stem Leydig cells Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
                                                                                                                                                    657 Decreased testosterone by the fetal Leydig cells, Dysgenesis of fetal Leydig cells Organ Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
                                                                                                                                                    540 Decreased testosterone by the fetal Leydig cells, Dysgensis of fetal Leydig cells Organ Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
                                                                                                                                                    662 Decreased testosterone by the fetal Leydig cells, Hypermethylation in the fetal testis Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
                                                                                                                                                    653 Decreased testosterone by the fetal Leydig cells, Increased corticosterone Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
                                                                                                                                                    655 Decreased testosterone by the fetal Leydig cells, Increased COUP-TFII in fetal Leydig cells Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
                                                                                                                                                    658 Decreased testosterone by the fetal Leydig cells, Increased estradiol Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
                                                                                                                                                    1756 Decreased, plasma 11-ketotestosterone level Tissue Mar 23, 2020 May 24, 2022
                                                                                                                                                    • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                    • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                    • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                    8 Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                    1401 Decreased, 5-HT3 Tissue Jun 1, 2017 Jun 1, 2017
                                                                                                                                                    • Serotonin transporter activation to seizure
                                                                                                                                                    1881 Decreased, all-trans retinoic acid (atRA) concentration Tissue May 24, 2021 Feb 13, 2023
                                                                                                                                                    • 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
                                                                                                                                                    1987 Decreased, Androgen and Progestin Cellular Apr 5, 2022 Jun 6, 2022
                                                                                                                                                    • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                    742 Decreased, Androgen receptor activity Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                    1409 Decreased, angiogenesis Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                    • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                    627 Decreased, anxiety Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                    1183 Decreased, Apoptosis (Epithelial Cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                    • Androgen receptor activation leading to prostate cancer
                                                                                                                                                    800 Decreased, Aromatase (Cyp19a1) mRNA Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                    • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                    2123 decreased, Bcl-2 expression Molecular Apr 4, 2023 Sep 7, 2023
                                                                                                                                                    • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                    1407 Decreased, bicarbonate Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                    • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                    1058 Decreased, bile flow Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                    848 Decreased, Binding of NE to NE receptors on GnRH neurons Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                    • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                    315 Decreased, Body length Nov 29, 2016 Nov 29, 2016
                                                                                                                                                      864 Decreased, Body Weight Individual Nov 29, 2016 Apr 30, 2019
                                                                                                                                                      • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                      52 Decreased, Calcium influx Cellular 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
                                                                                                                                                      656 Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) Cellular Nov 29, 2016 Apr 16, 2024
                                                                                                                                                      • Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
                                                                                                                                                      • Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
                                                                                                                                                      • Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
                                                                                                                                                      • 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
                                                                                                                                                      1178 Decreased, Chloride conductance Nov 29, 2016 Nov 29, 2016
                                                                                                                                                        807 Decreased, cholesterol Tissue Nov 29, 2016 May 24, 2022
                                                                                                                                                        • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                        • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                        533 Decreased, Cortical granule release/distribution upon fertilization Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                        • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                        • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                        527 Decreased, Decreased fecundity Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                        • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                        • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                        482 Decreased, DHB4/HSD17B4 Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                        • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                        1083 Decreased, Dopaminergic activity Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                        • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                        1319 Decreased, extracellular chloride (Cl-) Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                        1347 Decreased, extracellular serotonin Molecular Apr 14, 2017 May 31, 2017
                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                        • Mental stress to depression
                                                                                                                                                        • Mental stress to agitation
                                                                                                                                                        • Serotonin transporter activation to seizure
                                                                                                                                                        • Serotonin transporter activation to depression
                                                                                                                                                        • Serotonin transporter activation to agitation
                                                                                                                                                        • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                        1318 Decreased, extracellular sodium (Na+) Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                        • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                        1878 Decreased, Eye size Organ May 11, 2021 Jun 24, 2021
                                                                                                                                                        • Thyroperoxidase inhibition leading to altered visual function via decreased eye size
                                                                                                                                                        • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                        1414 Decreased, GABA Cellular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                        • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                        1179 Decreased, GABA release Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                        • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                        1145 Decreased, gametogenesis Nov 29, 2016 Nov 29, 2016
                                                                                                                                                          819 Decreased, Glomerular filtration Tissue Nov 29, 2016 Jun 19, 2024
                                                                                                                                                          • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                          • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                          578 Decreased, Glucose oxidase enzyme activity Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                          529 Decreased, GnRH cfos activity Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                          • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                          530 Decreased, GnRH pulsatility/release Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                          • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                          1071 Decreased, GnRH pulsatility/release in hypothalamus Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • 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.
                                                                                                                                                          1986 Decreased, Gonadotropins Molecular Apr 5, 2022 Apr 5, 2022
                                                                                                                                                          • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                          140 Decreased, HSD17B10 expression Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                          579 Decreased, Hydrogen peroxide production Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                          2214 Decreased, Insulin-like peptide 3 (INSL3) Molecular Mar 19, 2024 Apr 18, 2024
                                                                                                                                                          • Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
                                                                                                                                                          2121 decreased, Intellectual Quotient Population Apr 4, 2023 Apr 4, 2023
                                                                                                                                                          • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                          1416 Decreased, intracellular chloride Cellular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                          1323 Decreased, intracellular serotonin Molecular Apr 13, 2017 May 31, 2017
                                                                                                                                                          • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                          • Mental stress to depression
                                                                                                                                                          • Mental stress to agitation
                                                                                                                                                          • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                          1177 Decreased, Ionotropic GABA receptor chloride channel conductance Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                          477 Decreased, Ketogenesis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                          861 Decreased, Ketogenesis (production of ketone bodies) Cellular Nov 29, 2016 Apr 30, 2019
                                                                                                                                                          • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                          531 Decreased, LH Surge Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                          • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                          • Reduced availability of GnRH leading to uterine adenocarcinoma via increased estrogen availability at target organ level
                                                                                                                                                          1072 Decreased, LH Surge from anterior pituitary Cellular 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.
                                                                                                                                                          635 Decreased, locomotion Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                          166 Decreased, Long-term potentiation (LTP) Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                          168 Decreased, Lymphocytes Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                          1988 Decreased, Maturation Inducing Steroid Surge by Granulosa cells Tissue Apr 5, 2022 Apr 5, 2022
                                                                                                                                                          • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                          805 Decreased, mevalonate Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                          860 Decreased, Mitochondrial Fatty Acid Beta Oxidation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                          179 Decreased, Mitochondrial fatty acid beta-oxidation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                          • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                          • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                          1404 Decreased, mucosal blood flow Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                          1406 Decreased, mucous Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                          • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                          2105 Decreased, myelin basic protein expression in oligodendrocytes Molecular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                          • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                                                                                                                          2111 Decreased, neural progenitor cell adhesion to laminin Cellular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                          • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                                                                                          618 Decreased, Neuronal network function in adult brain Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • 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
                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                          1330 Decreased, neuroplasticity Molecular Apr 13, 2017 May 31, 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
                                                                                                                                                          193 Decreased, Nitric Oxide Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                          2116 Decreased, oligodendrocyte differentiation Cellular Feb 22, 2023 Feb 22, 2023
                                                                                                                                                          • Unknown MIE altering cholesterol metabolism leading to decreased cognition
                                                                                                                                                          • Increased reactive oxygen species production leading to decreased cognitive function
                                                                                                                                                          • Inhibition of voltage-gated sodium channels leading to decreased cognition
                                                                                                                                                          1045 Decreased, Ovarian E2 Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                          • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                          2074 Decreased, oxygen binding capacity by hemocyanin Molecular Nov 16, 2022 Nov 16, 2022
                                                                                                                                                          • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                          1324 Decreased, packaged serotonin Molecular Apr 13, 2017 May 31, 2017
                                                                                                                                                          • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                          • Mental stress to depression
                                                                                                                                                          • Mental stress to agitation
                                                                                                                                                          • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                          216 Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                          • AhR activation leading to hepatic steatosis
                                                                                                                                                          859 Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                            765 Decreased, population 1 Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                            • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                            992 Decreased, Population 2 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                              997 Decreased, Population size Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                              442 Decreased, Population trajectory Population Nov 29, 2016 Apr 18, 2017
                                                                                                                                                              • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                              • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                              231 Decreased, PPAR-alpha activation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                              • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                              232 Decreased, PPAR-beta activation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                              • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                              233 Decreased, PPAR-gamma activation Molecular Nov 29, 2016 Oct 30, 2023
                                                                                                                                                              • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                              • Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
                                                                                                                                                              858 Decreased, PPARalpha transactivation of gene expression Molecular Nov 29, 2016 Apr 30, 2019
                                                                                                                                                              • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                              749 Decreased, Progesterone from corpus luteum Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                              • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                              747 Decreased, Prolactin Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                              • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                              1104 Decreased, Prostaglandin F2alpha concentration, plasma Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                              • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                              681 Decreased, Prostaglandin F2alpha synthesis, ovary Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                              2113 Decreased, radial glia cell density Cellular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                              • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                                                                                              1055 Decreased, Reduced estradiol in circulation decreases estrogen concentration at hypothalamus Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                825 Decreased, Renal ability to dilute urine Organ Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                820 Decreased, Renal plasma flow Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                1141 Decreased, Reproductive Success Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                • 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
                                                                                                                                                                • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                1327 Decreased, seizure Individual Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                  1317 Decreased, serotonin transporter activity Molecular Apr 13, 2017 May 31, 2017
                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                  • Mental stress to depression
                                                                                                                                                                  • Mental stress to agitation
                                                                                                                                                                  • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                  1022 Decreased, serum T4/T3 Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                    629 Decreased, sheltering Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                    585 Decreased, Sodium conductance 1 Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                    • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                    • sodium channel inhibition leading to increased predation
                                                                                                                                                                    • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                    • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                    1176 Decreased, sodium conductance 2 Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                    • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                                    821 Decreased, Sodium reabsorption Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                    • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                    636 Decreased, survival Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                    • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                    • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                    1325 Decreased, synaptic release Molecular Apr 13, 2017 May 31, 2017
                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                    • Mental stress to depression
                                                                                                                                                                    • Mental stress to agitation
                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                    989 Decreased, synthesis and secretion of molting fluid proteases Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                      994 Decreased, Synthesis of molting fluid proteases Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                        528 Decreased, Synthesis of NE Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                        • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                                        743 Decreased, Testosterone binding to androgen receptor (hypothalamus) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                        • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                        2104 Decreased, thyroid hormone binding to thyroid hormone receptor Molecular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                                        • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                                                                                                                                        1093 Decreased, Thyroxine (T4) in tissues Tissue Nov 29, 2016 Sep 3, 2020
                                                                                                                                                                          1003 Decreased, Triiodothyronine (T3) Tissue 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
                                                                                                                                                                          • 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
                                                                                                                                                                          • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                          • 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
                                                                                                                                                                          1116 Decreased, Triiodothyronine (T3) in tissues Tissue Nov 29, 2016 Sep 1, 2020
                                                                                                                                                                          • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                          • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                          737 Decreased, Uptake of inorganic iodide Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                            304 Decreased, VegfR2 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                              2147 Decreased, Viable Offspring Individual Jun 2, 2023 Apr 10, 2024
                                                                                                                                                                              • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                              • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                              1295 Defect of Embryogenesis Tissue Feb 15, 2017 Sep 16, 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
                                                                                                                                                                              890 Degeneration of dopaminergic neurons of the nigrostriatal pathway Organ Nov 29, 2016 Mar 15, 2018
                                                                                                                                                                              • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                              • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                              428 Delay, Developmental GABA shift Cellular Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                2047 Delay, Ovarian maturation Cellular Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                532 Delayed, Ovulation Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                                                • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                                                1140 Delayed, Sexual maturity Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  2142 Depletion, Ectoplasmic specialization (ES) Cellular May 17, 2023 May 17, 2023
                                                                                                                                                                                  • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                  1143 Depletion, energy reserves Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                  130 Depletion, GSH Cellular Nov 29, 2016 Sep 14, 2023
                                                                                                                                                                                  • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                  1482 Depletion, mtDNA Cellular Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                  • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                  1686 Deposition of Energy Molecular Aug 22, 2019 Mar 8, 2024
                                                                                                                                                                                  • Deposition of energy leading to lung cancer
                                                                                                                                                                                  • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                  • 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
                                                                                                                                                                                  • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                  • 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 oocyte apoptosis
                                                                                                                                                                                  • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                  • 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
                                                                                                                                                                                  • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                  • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                  • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                  • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                  • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                  1550 Deposition of Ionizing Energy Molecular Dec 19, 2018 Dec 13, 2021
                                                                                                                                                                                  • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                  2138 Derease, testosterone levels Tissue May 16, 2023 May 8, 2024
                                                                                                                                                                                    663 Desensitization, Nicotinic acetylcholine receptor Molecular Nov 29, 2016 Jun 7, 2018
                                                                                                                                                                                    • 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 roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                    2189 Development-related pathway alterations Cellular Sep 16, 2023 Sep 17, 2023
                                                                                                                                                                                      2035 development, liver cancer Tissue Jul 21, 2022 Jul 21, 2022
                                                                                                                                                                                        1272 Differentiation of Myofibroblast Cellular Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                          944 dimerization, AHR/ARNT Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                          • 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
                                                                                                                                                                                          • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                          • AhR activation leading to preeclampsia
                                                                                                                                                                                          • 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
                                                                                                                                                                                          1869 Diminished protective oxidative stress response Cellular Apr 20, 2021 Oct 30, 2023
                                                                                                                                                                                          • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                          • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                          • SARS-CoV-2 infection leading to pyroptosis
                                                                                                                                                                                          • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                          • Increased reactive oxygen species production leading to decreased cognitive function
                                                                                                                                                                                          652 Direct effects of Corticosterone on steroidogenesis, Decreased testosterone by adult Leydig cells Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                          • Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
                                                                                                                                                                                          1958 Direct hERG channel blockage Cellular Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                            1260 Direct mitochondrial inhibition Molecular Feb 7, 2017 Sep 16, 2017
                                                                                                                                                                                            • AOP from chemical insult to cell death
                                                                                                                                                                                            721 Disorganization, Meiotic Spindle Cellular Nov 29, 2016 Apr 20, 2021
                                                                                                                                                                                            • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                            1830 Displacement, Serum thyroxine (T4) from carrier protein Molecular 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
                                                                                                                                                                                            958 Displacement, Serum thyroxine (T4) from transthyretin Molecular Nov 29, 2016 Dec 17, 2016
                                                                                                                                                                                            • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                            2110 Disrupted binding, laminin-beta1-integrin receptors with laminin Molecular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                                                            • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                                                                                                                            2225 Disrupted Lipid Storage Cellular May 8, 2024 May 23, 2024
                                                                                                                                                                                            • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                            1882 Disrupted meiotic initiation of fetal oogonia of the ovary Cellular May 24, 2021 Feb 27, 2022
                                                                                                                                                                                            • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                            2227 Disrupted PPAR isoform nuclear signaling Molecular May 14, 2024 May 22, 2024
                                                                                                                                                                                            • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                            1977 Disruption of sodium channel gating kinetics Cellular Mar 15, 2022 Sep 13, 2022
                                                                                                                                                                                            • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                            • Inhibition of voltage-gated sodium channels leading to decreased cognition
                                                                                                                                                                                            1983 Disruption, action potential Cellular Mar 31, 2022 Mar 31, 2022
                                                                                                                                                                                            • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                            2141 Disruption, Estrogen receptor Molecular May 17, 2023 May 17, 2023
                                                                                                                                                                                            • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                            1536 Disruption, Intracellular calcium mobilization Cellular Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                            898 Disruption, Lysosome Cellular Nov 29, 2016 Nov 12, 2018
                                                                                                                                                                                            • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                            • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                            • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                            169 Disruption, Membrane integrity Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                            • Narcosis leading to respiratory failure
                                                                                                                                                                                            720 Disruption, Microtubule dynamics Molecular Nov 29, 2016 Nov 7, 2019
                                                                                                                                                                                            • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                            178 Disruption, Mitochondrial electron transport chain Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                            • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                            • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                                                                                                                            1681 Disruption, Neural crest cell migration Cellular Aug 13, 2019 Aug 13, 2019
                                                                                                                                                                                            • TBX1 inhibition leading to congenital cardiac conotruncal anomalies
                                                                                                                                                                                            2151 Disruption, neurotransmitter release Molecular Jun 27, 2023 Jul 21, 2023
                                                                                                                                                                                            • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                            1682 Disruption, Progenitor cells of second heart field Cellular Aug 13, 2019 Feb 15, 2022
                                                                                                                                                                                            • TBX1 inhibition leading to congenital cardiac conotruncal anomalies
                                                                                                                                                                                            • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                            1537 Disruption, Sarcomere assembly Cellular Jun 21, 2018 Jun 21, 2018
                                                                                                                                                                                            • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                            1590 Distribution and deposition of chemicals to skin and/or eyes Molecular Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                              1581 Disturbance in microtubule dynamic instability Cellular Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                              • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                              831 Disturbance, Lysosomal function Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                              • Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
                                                                                                                                                                                              2114 Disturbed, cortical architecture Organ Feb 21, 2023 Feb 21, 2023
                                                                                                                                                                                              • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                                                                                                                              2112 Disturbed, radial glia cell alignment and migration Cellular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                                                              • Binding to the extracellular protein laminin leading to decreased cognitive function
                                                                                                                                                                                              1388 Dopamine release in the brain, decreased Tissue 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
                                                                                                                                                                                              472 Down Regulation, CPT1A Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                              • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                              • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                                                                                                                                                                              1286 Down Regulation, GSS and GSTs gene Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                              • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                              131 Down Regulation, Gulcose-6-phosphate dehydrogenase Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                              • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                              474 Down Regulation, HMGCS2 Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                              • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                              427 Down Regulation, K-Cl co-transporter 2 (KCC2) Cellular Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                1787 Downregulation, ACE2 Cellular May 15, 2020 Mar 31, 2021
                                                                                                                                                                                                • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                                                                                                                                                                2088 Dysfunction of respiratory system Individual Jan 9, 2023 Jan 9, 2023
                                                                                                                                                                                                • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                1184 Dysfunction, Mitochondrial Dynamics Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                  1945 Dysfunctional Autophagy Cellular 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
                                                                                                                                                                                                  • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                  1850 dysgeusia Organ Mar 28, 2021 Apr 26, 2021
                                                                                                                                                                                                  • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                  1703 Dysregulation of heart rate and vascular tone Organ Nov 25, 2019 Dec 20, 2019
                                                                                                                                                                                                  • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                  2224 Dysregulation of transcriptional expression within PPAR signaling network Molecular May 8, 2024 May 23, 2024
                                                                                                                                                                                                  • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                  1854 Dysregulation, ACE2 expression and activity Molecular Mar 31, 2021 Feb 18, 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
                                                                                                                                                                                                  • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                  1600 Eczematous eruption (Erythema, Papules, Vesicles, Pruritius, Weeping, Oozing, Crusting) Organ Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                    1248 EGFR , Activation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                      1247 EGFR , PPAR-alpha activation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                        222 Elimination of (high doses), Posterior cardinal vein Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                          2011 Emphysema Organ May 31, 2022 May 31, 2022
                                                                                                                                                                                                          • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                          1841 Encephalitis Organ 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
                                                                                                                                                                                                          1539 Endocytotic lysosomal uptake Molecular Nov 6, 2018 Apr 17, 2024
                                                                                                                                                                                                          • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                          • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                          2017 Endoplasmic reticulum stress Cellular Jun 27, 2022 Jun 27, 2022
                                                                                                                                                                                                          • PM2.5-related AOP frameworks on liver diseases
                                                                                                                                                                                                          • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                          2175 Endothelial cell death Cellular Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                            1913 Endothelial cell dysfunction Cellular Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                            • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                            • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                            2212 Epididymal agenesis Organ Mar 19, 2024 Apr 16, 2024
                                                                                                                                                                                                            • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                            2152 Epigenetic modification process Cellular Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                            • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                            1457 Epithelial Mesenchymal Transition Cellular Jul 26, 2017 Apr 24, 2024
                                                                                                                                                                                                            • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                            • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                            • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                            • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway
                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway
                                                                                                                                                                                                            • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                            • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                            • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                            1180 Estrogen receptor activation, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                              2126 Estrogen receptor alpha inactivation Molecular Apr 5, 2023 Apr 10, 2023
                                                                                                                                                                                                              • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                              • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                              1714 Exacerbation of systemic lupus erythematosus (SLE) Individual Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                              • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                              1859 Excitation of intracellular water Molecular Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                1217 Excitation of trigeminal nerves induces Sensory Airway Irritation, Organ Nov 29, 2016 Sep 24, 2018
                                                                                                                                                                                                                  1273 Expression of Collagen Cellular Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                    2153 Expression of factors ruling proliferation, modified Cellular Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                                    • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                    1905 eya1 expression, inhibited Molecular Jul 14, 2021 Oct 7, 2021
                                                                                                                                                                                                                    • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                    1559 Facial cartilage structures are reduced in size and morphologically distorted Tissue Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                    • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
                                                                                                                                                                                                                    1131 Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                    1119 Failure in gamma-glutamyl carboxylation of glutamine residues on clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                      1130 Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                      • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                      1528 Fatty Acid Beta Oxidation, Decreased Molecular Jun 11, 2018 Apr 30, 2019
                                                                                                                                                                                                                      • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                      240 Feminisation or incomplete development, Primary and accessory male sex organs Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                      • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                      1866 Fibrinolysis, decreased Molecular Apr 20, 2021 Oct 19, 2021
                                                                                                                                                                                                                      • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                      2012 Fibroblast proliferation and differentiation Cellular May 31, 2022 May 31, 2022
                                                                                                                                                                                                                      • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                      1587 Fibroproliferative airway lesions Tissue Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                      • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                      1442 Foam cell formation Organ Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                        1597 Formation of DNA photo-adducts Cellular Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                                          1440 Formation of HDL-SAA Cellular Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                            1899 formation of neutrophil extracellular traps (NETs) Cellular 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)
                                                                                                                                                                                                                            1598 Formation of protein photo-adducts Cellular Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                                              118 Formation, Formation of hemoglobin adducts Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                              • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                              856 Formation, Hepatocellular and Bile duct tumors Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                              • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                                                                                                                                              840 Formation, Liver fibrosis Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                              347 Formation, Liver tumor Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                              • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                              839 Formation, Mallory body Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                              373 Formation, Pro-mutagenic DNA Adducts Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                              • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                              976 Formation, The binding of FK506 with FKBP12 Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                1903 foxi1 expression, increased Molecular Jul 14, 2021 Oct 28, 2021
                                                                                                                                                                                                                                • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                1911 FOXJ1 Protein, Decreased Cellular Jul 23, 2021 Sep 10, 2021
                                                                                                                                                                                                                                • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                1646 Frizzled activation Molecular May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                  1668 Frustrated phagocytosis Cellular Jul 3, 2019 Sep 16, 2022
                                                                                                                                                                                                                                  • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                  • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                  1932 Gastrointestinal disorders Individual Sep 2, 2021 Sep 8, 2021
                                                                                                                                                                                                                                    1513 General Apoptosis Cellular Apr 4, 2018 Oct 18, 2023
                                                                                                                                                                                                                                    • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                    1236 Generation of novel epitopes , Antigen presentation Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                      682 Generation, Amplified excitatory postsynaptic potential (EPSP) Cellular Nov 29, 2016 May 18, 2018
                                                                                                                                                                                                                                      • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                      1896 Genomic instability Cellular Jul 6, 2021 Jul 6, 2021
                                                                                                                                                                                                                                      • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                      • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                      1953 Gestational diabetes mellitus Individual Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                      • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                      494 Glucocorticoid Receptor Agonist, Activation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                      • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                      651 Glucocorticoid Receptor mediated alterations in steriodogenic enzymes, Decreased testosterone by adult Leydig cells Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                      • Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
                                                                                                                                                                                                                                      1488 Glutamate dyshomeostasis Cellular Nov 9, 2017 Jul 15, 2022
                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                      1290 Glutathione homeostasis Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                      • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                      1287 Glutathione synthesis Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                      • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                      1519 Glycolysis Cellular May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                        1800 Granulosa cell proliferation of gonadotropin-independent follicles, Reduced Cellular Oct 13, 2020 Apr 20, 2022
                                                                                                                                                                                                                                        • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                        1467 Growth, reduction Individual Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                        • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                        1647 GSK3beta inactivation Molecular May 29, 2019 Oct 5, 2021
                                                                                                                                                                                                                                        • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                        1954 Gut microbiota, alteration Organ Nov 30, 2021 Jan 4, 2022
                                                                                                                                                                                                                                        • Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
                                                                                                                                                                                                                                        1535 Heart failure Organ Jun 19, 2018 Jun 19, 2018
                                                                                                                                                                                                                                        • L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
                                                                                                                                                                                                                                        • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                        • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                        • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                                                                                                                                                                                                        1412 Helicobacter pylori infection Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                        • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                        1124 Hemorrhage , Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                          1121 Hemorrhage , organ dysfunction, hypovolemic shock Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                            1123 Hemorrhage, organ dysfunction, hypovolemic shock, Impaired oxygen delivery to tissue Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                              1133 Hemostasis, Depletion from blood of fully functional carboxylated clotting factors Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                              • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                              2016 Hepatocyte cell apoptosis Cellular Jun 7, 2022 Jun 7, 2022
                                                                                                                                                                                                                                                1393 Hepatocytotoxicity Cellular May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                1291 Hepatotoxicity Cellular Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                1957 hERG channel biogenesis interference Molecular Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                  2099 hERG channel blockade Molecular Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                  • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                  757 Hippocampal anatomy, Altered Tissue Nov 29, 2016 May 20, 2022
                                                                                                                                                                                                                                                  • Inhibition of Thyroperoxidase 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
                                                                                                                                                                                                                                                  • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                  • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                  • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                  • Binding to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                  756 Hippocampal gene expression, Altered Tissue Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                                                                  • Inhibition of Thyroperoxidase 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
                                                                                                                                                                                                                                                  • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                  • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                  758 Hippocampal Physiology, Altered Tissue Nov 29, 2016 Aug 11, 2018
                                                                                                                                                                                                                                                  • Inhibition of Thyroperoxidase 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
                                                                                                                                                                                                                                                  • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                  • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                  • Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                  • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                  1503 Histone acetylation, increase Cellular Jan 21, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                  • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                  1502 Histone deacetylase inhibition Molecular Jan 21, 2018 Jul 14, 2022
                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                  • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                  • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                  1853 Hyperactivation of ACE/Ang-II/AT1R axis Molecular Mar 31, 2021 Mar 31, 2021
                                                                                                                                                                                                                                                  • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                  • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                                                                                                                                                                                                                  1868 Hyperinflammation Tissue Apr 20, 2021 Dec 29, 2021
                                                                                                                                                                                                                                                  • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                  • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                  • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                  • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                  1943 Hyperphosphorylation of Tau Cellular 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
                                                                                                                                                                                                                                                  142 Hyperplasia, Hyperplasia Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                  • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                                                  415 Hyperplasia, Leydig cell Cellular Nov 29, 2016 Sep 27, 2017
                                                                                                                                                                                                                                                  • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                  1078 Hyperplasia, Mammary gland Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                  • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                  1052 Hyperplasia, ovarian epithelium Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                  1051 Hyperplasia, ovarian stromal cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                  • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                  763 hyperpolarisation, neuron Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                  • Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening
                                                                                                                                                                                                                                                  • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
                                                                                                                                                                                                                                                  943 Hypersecretion, Mucus Organ Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                    952 Hypertension Individual Nov 29, 2016 Sep 27, 2017
                                                                                                                                                                                                                                                    • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                    • Na+ /K+ -ATPase inhibition leading to hypertension
                                                                                                                                                                                                                                                    1043 Hypertrophy/hyperplasia, smooth muscle Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                    • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                    1095 hyperuricemia, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                      2107 Hypomyelination Tissue Feb 21, 2023 Feb 21, 2023
                                                                                                                                                                                                                                                      • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                                                                                                                                                                                                                      • Unknown MIE altering cholesterol metabolism leading to decreased cognition
                                                                                                                                                                                                                                                      • Increased reactive oxygen species production leading to decreased cognitive function
                                                                                                                                                                                                                                                      • Inhibition of voltage-gated sodium channels leading to decreased cognition
                                                                                                                                                                                                                                                      • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                      2082 Hypospadias, increased Organ Dec 18, 2022 Apr 16, 2024
                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to hypospadias in male offspring
                                                                                                                                                                                                                                                      • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                      1819 IFNγ signaling Cellular Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                      • Immune mediated hepatitis
                                                                                                                                                                                                                                                      1856 Imbalanced salty and sweet taste responses Tissue Apr 7, 2021 Apr 7, 2021
                                                                                                                                                                                                                                                      • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                      1818 Immune cell activation Cellular Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                      • Immune mediated hepatitis
                                                                                                                                                                                                                                                      2180 Immune mechanisms antagonized by viral proteins Molecular Aug 23, 2023 Dec 13, 2023
                                                                                                                                                                                                                                                      • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                      1820 Immune mediated hepatitis Organ Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                      • Immune mediated hepatitis
                                                                                                                                                                                                                                                      1225 Immune system inflammation Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                        1644 Impaired Ab production Cellular May 23, 2019 Jun 25, 2019
                                                                                                                                                                                                                                                          1568 Impaired antigen presentation Organ Dec 24, 2018 Dec 24, 2018
                                                                                                                                                                                                                                                            1582 Impaired axonial transport Cellular Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                            • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                            1705 Impaired coordination and movement Individual Dec 20, 2019 Dec 20, 2019
                                                                                                                                                                                                                                                            • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                            364 Impaired development of, Reproductive organs Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                            • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                            1849 Impaired gustatory nerve Tissue Mar 28, 2021 Apr 7, 2021
                                                                                                                                                                                                                                                            • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                            1572 Impaired IL-1 signaling Molecular Dec 24, 2018 Jun 24, 2019
                                                                                                                                                                                                                                                              1700 Impaired IL-1R1 signaling in T cell Molecular Nov 17, 2019 Mar 2, 2023
                                                                                                                                                                                                                                                              • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                              1615 Impaired inguinoscrotal testicular descent phase Organ Apr 10, 2019 Apr 18, 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
                                                                                                                                                                                                                                                              2144 Impaired insulin signaling Cellular 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
                                                                                                                                                                                                                                                              1833 Impaired lung function Individual Jan 8, 2021 Feb 16, 2021
                                                                                                                                                                                                                                                                1946 Impaired mechanotransduction of pericytes Cellular Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                1873 impaired olfactory function (anosmia) Organ Apr 25, 2021 Mar 30, 2022
                                                                                                                                                                                                                                                                • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                1695 Impaired ovulation Organ Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                1125 Impaired oxygen and nutrient delivery to tissue, impaired removal of carbon dioxide and other waste products, Hemorrhage, organ dysfunction and hypovolemic shock Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                  1678 Impaired oxygenation of the blood Organ Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                    2179 Impaired Platelet Aggregation Tissue Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                    1136 Impaired recruitment , Population trajectory Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                    1569 Impaired T cell activation Cellular Dec 24, 2018 Jun 25, 2019
                                                                                                                                                                                                                                                                      2080 Impaired, blood testis barrier Organ Dec 13, 2022 Dec 13, 2022
                                                                                                                                                                                                                                                                      • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                      577 impaired, Development Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                      • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                      406 impaired, Fertility Individual Nov 29, 2016 Sep 14, 2023
                                                                                                                                                                                                                                                                      • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                      • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                      • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                      • Inhibition of 11β-hydroxylase leading to decresed population trajectory
                                                                                                                                                                                                                                                                      • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                      • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                                                                                                      • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                      • Androgen receptor (AR) antagonism leading to decreased fertility in females
                                                                                                                                                                                                                                                                      568 impaired, Hive thermoregulation Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                      • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                      • Suppression of immune system contributes to impaired development and leads to colony loss/failure
                                                                                                                                                                                                                                                                      • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                      697 impaired, ion channels Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                      • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                      566 impaired, Larval development Population 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
                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                      637 impaired, Learning and memory Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                      2106 Impaired, oligodendrocyte maturation Cellular Feb 21, 2023 Feb 21, 2023
                                                                                                                                                                                                                                                                      • Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
                                                                                                                                                                                                                                                                      1989 Impaired, Oocyte maturation and ovulation Tissue Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                      • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                      889 Impaired, Proteostasis Cellular Nov 29, 2016 Mar 15, 2018
                                                                                                                                                                                                                                                                      • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                      • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                      1991 Impaired, Reproduction Population Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                      • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                      1758 Impaired, Spermatogenesis Organ Apr 16, 2020 Apr 10, 2024
                                                                                                                                                                                                                                                                      • PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
                                                                                                                                                                                                                                                                      • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                      • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                      • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
                                                                                                                                                                                                                                                                      583 impaired, Thoracic shivering Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                        2213 Impaired, urethral tube closure Organ Mar 19, 2024 Apr 16, 2024
                                                                                                                                                                                                                                                                        • Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
                                                                                                                                                                                                                                                                        1667 Impaired,anterior-posterior axis development Individual Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                        • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                        1719 Impairment of T-cell dependent antibody response Individual Jan 5, 2020 Feb 24, 2021
                                                                                                                                                                                                                                                                        • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                        986 Impairment of TDAR Individual Nov 29, 2016 Mar 2, 2023
                                                                                                                                                                                                                                                                          110 Impairment, Endothelial network Cellular Nov 29, 2016 Jan 18, 2022
                                                                                                                                                                                                                                                                          • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                          • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                          1683 Impairment, Fourth pharyngeal arch development Tissue Aug 13, 2019 Aug 13, 2019
                                                                                                                                                                                                                                                                          • TBX1 inhibition leading to congenital cardiac conotruncal anomalies
                                                                                                                                                                                                                                                                          341 Impairment, Learning and memory Individual Nov 29, 2016 Jun 26, 2023
                                                                                                                                                                                                                                                                          • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                          • 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 Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading 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 abnormal roll change within the worker bee caste leading to colony loss/failure 2
                                                                                                                                                                                                                                                                          • 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
                                                                                                                                                                                                                                                                          • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                          • 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 to voltage gate sodium channels during development leads to cognitive impairment
                                                                                                                                                                                                                                                                          • Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
                                                                                                                                                                                                                                                                          • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                          • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                          • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                          • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                          • Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                          • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                          984 Impairment, T-cell dependent antibody response Individual Nov 29, 2016 Feb 19, 2023
                                                                                                                                                                                                                                                                          • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                          • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                          1328 Inactivated, 5-HTR (serotonin receptors) Molecular Apr 13, 2017 May 31, 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
                                                                                                                                                                                                                                                                          1270 Inactivation of PPARγ Molecular Feb 15, 2017 Dec 26, 2017
                                                                                                                                                                                                                                                                          • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                          • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                          1356 Inactive, membrane depolarization Molecular Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                          • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                          155 Inadequate DNA repair Cellular 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
                                                                                                                                                                                                                                                                          • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                          • Bulky DNA adducts leading to mutations
                                                                                                                                                                                                                                                                          • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                          • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                          • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                          1552 Inadequate DNA repair (deprecated, please use https://aopwiki.org/events/155) Molecular Dec 19, 2018 Jan 25, 2019
                                                                                                                                                                                                                                                                            1555 Increase cell proliferation Cellular Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                            • AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
                                                                                                                                                                                                                                                                            1554 Increase Chromosomal Aberrations Molecular Dec 19, 2018 Aug 27, 2023
                                                                                                                                                                                                                                                                            • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                            1633 Increase in inflammation Tissue May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                            • Immune mediated hepatitis
                                                                                                                                                                                                                                                                            • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                            • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                            1632 Increase in reactive oxygen and nitrogen species (RONS) Molecular May 3, 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
                                                                                                                                                                                                                                                                            • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                            1553 Increase mutations Molecular Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                              1713 Increase of anti-DNA antibody from autoreactive B cell Cellular Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                              • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                              1712 Increase of Th2 cells producing IL-4 Cellular Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                              • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                              2073 increase oxidation of the di-copper moiety of the hemocyanin active site Molecular Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                              • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                              1743 Increase plasma Ang II Tissue Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                              • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                              416 Increase proliferation, Leydig cell Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                              • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                              1978 Increase risk, microcephaly Individual Mar 17, 2022 Mar 18, 2022
                                                                                                                                                                                                                                                                              • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                              • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                              2056 Increase, delay in oviposition Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                              • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                              2054 Increase, impairment of cuticle sclerotization Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                              • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                              2055 Increase, pigmentation Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                              • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                              2098 Increase, Abnormal Neural Remodeling Tissue Jan 25, 2023 Mar 10, 2024
                                                                                                                                                                                                                                                                              • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                              1768 Increase, Abnormal osmoregulation Tissue Apr 30, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                              736 Increase, Adenomas/carcinomas (bronchioloalveolar) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                              • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                              741 Increase, Adenomas/carcinomas (follicular cell) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                              713 Increase, Adenomas/carcinomas (renal tubular) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                              • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                              • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                              797 Increase, Adenomas/carcinomas (urothelial) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                              • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                              2045 Increase, Alcohol dehydrogenase Molecular Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                              • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                              313 Increase, Allergic Respiratory Hypersensitivity Response Organ Nov 29, 2016 Feb 7, 2023
                                                                                                                                                                                                                                                                              • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                              1384 Increase, ammonium (NH4+) Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                              • Gastric ulcer formation
                                                                                                                                                                                                                                                                              • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                              2134 Increase, Androgen receptor Molecular May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                              • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                              728 Increase, Aneuploid offspring Individual Nov 29, 2016 May 27, 2019
                                                                                                                                                                                                                                                                              • Chemical binding to tubulin in oocytes leading to aneuploid offspring
                                                                                                                                                                                                                                                                              1376 Increase, angiogenesis Tissue Apr 17, 2017 Feb 29, 2024
                                                                                                                                                                                                                                                                              • Gastric ulcer formation
                                                                                                                                                                                                                                                                              • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                              1365 Increase, Apoptosis Cellular Apr 15, 2017 Apr 15, 2017
                                                                                                                                                                                                                                                                              • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                              • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                              • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                              • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                              • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                              • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                              1372 Increase, bicarbonate Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                              • Gastric ulcer formation
                                                                                                                                                                                                                                                                              401 Increase, Biliary excretion TH glucuronide Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                1769 Increase, Body fluid overload Tissue Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                2048 Increase, Body volume of female adults Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                2090 Increase, Bone Remodeling Tissue Jan 11, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                50 Increase, Ca++ (intracellular) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                885 Increase, Cancer Tissue Nov 29, 2016 Aug 22, 2023
                                                                                                                                                                                                                                                                                • Alkylation of DNA leading to cancer 2
                                                                                                                                                                                                                                                                                • Alkylation of DNA leading to cancer 1
                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                2084 Increase, Cardiac remodelling Tissue Jan 5, 2023 Jan 5, 2023
                                                                                                                                                                                                                                                                                • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                1774 Increase, Caspase transcription Molecular 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 population decline (3)
                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                                                                                                                                                                1779 Increase, Caspase transcription (F3) Molecular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                1825 Increase, Cell death Cellular Dec 4, 2020 Mar 22, 2023
                                                                                                                                                                                                                                                                                • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                • Mitochondrial complex III antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                • Cytochrome oxidase inhibition leading to olfactory nasal lesions
                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway
                                                                                                                                                                                                                                                                                • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                1527 Increase, Cell membrane depolarization Cellular May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                • Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
                                                                                                                                                                                                                                                                                870 Increase, Cell Proliferation Cellular Nov 29, 2016 Mar 8, 2024
                                                                                                                                                                                                                                                                                • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway
                                                                                                                                                                                                                                                                                • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                                • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                1182 Increase, Cell Proliferation (Epithelial Cells) Cellular Nov 29, 2016 May 8, 2019
                                                                                                                                                                                                                                                                                • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                716 Increase, cell proliferation (hepatocytes) Cellular Nov 29, 2016 Jan 6, 2021
                                                                                                                                                                                                                                                                                • 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)
                                                                                                                                                                                                                                                                                • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                1636 Increase, Chromosomal aberrations Cellular 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
                                                                                                                                                                                                                                                                                621 Increase, cilia movement Tissue Nov 29, 2016 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
                                                                                                                                                                                                                                                                                1171 Increase, Clonal Expansion of Altered Hepatic Foci Cellular Nov 29, 2016 Jan 6, 2021
                                                                                                                                                                                                                                                                                • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                2195 Increase, CNS Neural cell death Cellular Oct 17, 2023 Oct 17, 2023
                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                1334 Increase, cortisone Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                1269 Increase, COX-2 expression Molecular Feb 9, 2017 Mar 20, 2018
                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
                                                                                                                                                                                                                                                                                1759 Increase, Cripto-1 expression Cellular Apr 20, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                320 Increase, Curved body axis Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                  1812 Increase, Cytochrome c release Cellular Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                  • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                  2064 Increase, Cytosolic calcium Cellular Sep 13, 2022 Sep 13, 2022
                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
                                                                                                                                                                                                                                                                                  1305 Increase, cytosolic fatty acid Cellular Apr 12, 2017 Nov 27, 2017
                                                                                                                                                                                                                                                                                  • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                  768 Increase, Cytotoxicity Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                  • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                  • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                                                                                                                                                                                                                  770 Increase, Cytotoxicity (club cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                  776 Increase, Cytotoxicity (corneal cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                  780 Increase, Cytotoxicity (epithelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                  786 Increase, Cytotoxicity (hepatocytes) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                  709 Increase, Cytotoxicity (renal tubular cell) Cellular Nov 29, 2016 Mar 3, 2022
                                                                                                                                                                                                                                                                                  • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                                                  783 Increase, Cytotoxicity (tubular epithelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                  794 Increase, Cytotoxicity (urothelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                  • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                  1516 Increase, D1 protein antagonism Molecular May 24, 2018 Oct 7, 2020
                                                                                                                                                                                                                                                                                    1861 Increase, D1 protein deactivation Cellular Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                    2053 Increase, Defects in tanning of new cuticle Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                    2050 Increase, developmental abnormalities Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                    • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                    1456 Increase, Differentiation of fibroblasts Cellular Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                    • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                    1194 Increase, DNA damage Molecular 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
                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                    • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                    • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                                                                                                                                                                                                                                                                    • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                    1461 Increase, DNA double-strand breaks Molecular Aug 2, 2017 Nov 13, 2023
                                                                                                                                                                                                                                                                                    • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                                                                                                                                                                    • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                    • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                    • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                    1620 Increase, DNA hypomethylation Molecular Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                      1697 Increase, DNA methyltransferase expression Molecular Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                      • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                      1619 Increase, DNA methyltransferase inhibition Molecular 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)
                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                      • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                      1635 Increase, DNA strand breaks Molecular May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                      • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                      • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                      • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                      • 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 Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                      • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                      746 Increase, Dopaminergic activity Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                      • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                      947 Increase, Early Life Stage Mortality Individual Nov 29, 2016 Mar 22, 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 impeded craniofacial development
                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
                                                                                                                                                                                                                                                                                      103 Increase, Ecdysone receptor agonism Molecular Nov 29, 2016 May 24, 2018
                                                                                                                                                                                                                                                                                      • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                      773 Increase, Endometrial adenocarcinomas Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                      • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                      2068 Increase, Endothelial Dysfunction Tissue Sep 28, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                      • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                      573 Increase, Energetic demands and therefore metabolic stress Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                      • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                      1860 Increase, Excitation of intracellular water Molecular Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                        115 Increase, FA Influx Cellular Nov 29, 2016 Mar 29, 2024
                                                                                                                                                                                                                                                                                        • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                        • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                        1312 Increase, Fatty acid beta-oxidation Cellular Apr 13, 2017 Dec 4, 2020
                                                                                                                                                                                                                                                                                          1994 Increase, Ferroptosis Cellular Apr 7, 2022 Apr 7, 2022
                                                                                                                                                                                                                                                                                            1444 Increase, Follicular atresia Organ Jun 29, 2017 Nov 25, 2020
                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                            1765 Increase, Formation of DNA photoproducts Molecular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                            • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                            1265 Increase, Fushi tarazu factor-1 gene expression Molecular Feb 9, 2017 May 24, 2018
                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                            1361 Increase, GABA Molecular Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                            • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                            1621 Increase, Gene expression Molecular Apr 22, 2019 Apr 22, 2019
                                                                                                                                                                                                                                                                                              1175 Increase, Genes involved in fatty acid oxidation Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                1827 Increase, Global DNA methylation Molecular Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                2133 Increase, Glucuronidation of T4 Molecular Apr 12, 2023 Apr 12, 2023
                                                                                                                                                                                                                                                                                                  2070 Increase, Glycolysis Cellular Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                  • Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
                                                                                                                                                                                                                                                                                                  2117 Increase, goblet cell number Cellular Mar 8, 2023 Mar 8, 2023
                                                                                                                                                                                                                                                                                                  • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                  2137 Increase, Gonadotropins concentration in plasma Tissue May 16, 2023 May 16, 2023
                                                                                                                                                                                                                                                                                                  • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                  1480 Increase, Growth hormone Organ Oct 10, 2017 Feb 16, 2021
                                                                                                                                                                                                                                                                                                    2076 Increase, hemocyanin mRNA Tissue Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                    • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                    719 Increase, hepatocellular adenomas and carcinomas Tissue Nov 29, 2016 Dec 26, 2020
                                                                                                                                                                                                                                                                                                    • Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
                                                                                                                                                                                                                                                                                                    • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and 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)
                                                                                                                                                                                                                                                                                                    • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                    336 Increase, Heritable mutations in offspring Individual Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                    • Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
                                                                                                                                                                                                                                                                                                    1698 Increase, hypermethylation of the promotor region of gonadotropin releasing hormone receptor Molecular Oct 30, 2019 Oct 30, 2019
                                                                                                                                                                                                                                                                                                    • Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
                                                                                                                                                                                                                                                                                                    740 Increase, Hyperplasia (follicular cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                                    782 Increase, Hyperplasia (forestomach epithelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                    772 Increase, Hyperplasia (glandular epithelial cells of endometrium) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                    • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                    744 Increase, Hyperplasia (Leydig cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                    • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                    767 Increase, Hyperplasia (renal tubular cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                    735 Increase, Hyperplasia (terminal bronchiolar cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                    784 Increase, Hyperplasia (tubular epithelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                    796 Increase, Hyperplasia (urothelial) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                    • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                    1343 Increase, hypertension Individual Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                    739 Increase, Hypertrophy and proliferation (follicular cell) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                                    1707 Increase, IL-23 from matured dendritic cells Cellular Dec 27, 2019 Nov 23, 2020
                                                                                                                                                                                                                                                                                                    • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                    990 Increase, Incomplete ecdysis Individual Nov 29, 2016 May 24, 2018
                                                                                                                                                                                                                                                                                                    • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                    • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                    • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                    149 Increase, Inflammation Cellular Nov 29, 2016 Feb 28, 2024
                                                                                                                                                                                                                                                                                                    • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                    • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                    • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                    • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                    • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                    • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                    777 Increase, Inflammation (corneal cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                    • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                    1338 Increase, inositol triphosphate Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                    • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                    • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                    1296 Increase, insulin Molecular Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                      1339 Increase, intracellular calcium Cellular Apr 13, 2017 Jul 21, 2023
                                                                                                                                                                                                                                                                                                      • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                      • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                      • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
                                                                                                                                                                                                                                                                                                      • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                      1378 Increase, leukocyte adherence Tissue Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                      • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                      745 Increase, Leydig cell tumors Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                      • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                      • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                      161 Increase, Liver and splenic hemosiderosis Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                      1556 Increase, lung cancer Organ Dec 19, 2018 Jan 10, 2023
                                                                                                                                                                                                                                                                                                      • Deposition of energy leading to lung cancer
                                                                                                                                                                                                                                                                                                      414 Increase, Luteinizing hormone (LH) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                      1333 Increase, mental stress Individual Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                        1785 Increase, Mitochondrial ATP synthase antagonism Molecular May 8, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                        • Mitochondrial ATP synthase antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                        • Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                        1813 Increase, Mitochondrial complex I dysfunction Molecular Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                          1542 Increase, Mitochondrial complex III antagonism Molecular Dec 19, 2018 Dec 4, 2020
                                                                                                                                                                                                                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                          • Mitochondrial complex III antagonism leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                          • Mitochondrial complex III antagonism leading to growth inhibition (2)
                                                                                                                                                                                                                                                                                                          1811 Increase, Mitochondrial complex III dysfunction Molecular Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                            2072 Increase, Mitochondrial swelling Cellular Nov 1, 2022 Nov 1, 2022
                                                                                                                                                                                                                                                                                                            • Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
                                                                                                                                                                                                                                                                                                            350 Increase, Mortality Individual Nov 29, 2016 Oct 26, 2020
                                                                                                                                                                                                                                                                                                            • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                            • Formation of DNA photoproducts leading to growth inhibition (1)
                                                                                                                                                                                                                                                                                                            • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                            • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                            • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                            • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                            • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                            • Doda decarboxylase leading to mortality
                                                                                                                                                                                                                                                                                                            • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                            962 Increase, Mucin production Cellular Nov 29, 2016 Mar 9, 2023
                                                                                                                                                                                                                                                                                                            • EGFR Activation Leading to Decreased Lung Function
                                                                                                                                                                                                                                                                                                            1374 Increase, mucosal blood flow Tissue Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                            1373 Increase, mucous Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                            185 Increase, Mutations Molecular Nov 29, 2016 May 15, 2023
                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                            • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                            • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                            876 Increase, Mutations in Critical Genes Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                            • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                            • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                                                            1341 Increase, myosin light chain phosphorylation Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                            • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                            • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                            1607 Increase, Necrosis Tissue Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                            • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                            733 Increase, Necrosis (terminal bronchiolar cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                            • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                            1578 Increase, Necrotic tissue Tissue Jan 7, 2019 Jan 7, 2019
                                                                                                                                                                                                                                                                                                              1264 Increase, Nuclear receptor E75b gene expression Molecular Feb 9, 2017 May 24, 2018
                                                                                                                                                                                                                                                                                                              • Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
                                                                                                                                                                                                                                                                                                              1775 Increase, Oocyte apoptosis Cellular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (1)
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (3)
                                                                                                                                                                                                                                                                                                              • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                              1780 Increase, Oocyte apoptosis (F3) Cellular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (1)
                                                                                                                                                                                                                                                                                                              1526 Increase, Opening of voltage-dependent calcium channel Cellular May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                              • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                              • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                              1777 Increase, Ovarian follicle breakdown Organ Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                                                                                                                                                                                              1784 Increase, Ovarian follicle breakdown (F3) Organ Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                              1776 Increase, Ovarian somatic cell apoptosis Cellular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (2)
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to population decline (4)
                                                                                                                                                                                                                                                                                                              1783 Increase, Ovarian somatic cell apoptosis (F3) Cellular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                              • DNA methyltransferase inhibition leading to transgenerational effects (2)
                                                                                                                                                                                                                                                                                                              1634 Increase, Oxidative damage to DNA Molecular May 19, 2019 Mar 8, 2024
                                                                                                                                                                                                                                                                                                              • Oxidative DNA damage leading to chromosomal aberrations and mutations
                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                              • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                              1608 Increase, Oxidative DNA damage Molecular Mar 19, 2019 Mar 19, 2019
                                                                                                                                                                                                                                                                                                              • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                              • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                              769 Increase, Oxidative metabolism Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                              • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                              1969 Increase, Oxidative Stress Molecular Feb 4, 2022 Mar 3, 2022
                                                                                                                                                                                                                                                                                                              • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                              • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                              1279 Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                              • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                              1826 Increase, Oxygen consumption Cellular Dec 4, 2020 Dec 4, 2020
                                                                                                                                                                                                                                                                                                                1865 Increase, Oxygen-evolving complex damage Molecular Apr 11, 2021 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                • Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                779 Increase, Papillomas/carcinomas (squamous cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                358 Increase, Pericardial edema Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                  1173 Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                    1170 Increase, Phenotypic enzyme activity Cellular Nov 29, 2016 Dec 28, 2020
                                                                                                                                                                                                                                                                                                                    • PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
                                                                                                                                                                                                                                                                                                                    1892 increase, placental insufficiency Organ May 31, 2021 May 31, 2021
                                                                                                                                                                                                                                                                                                                    • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                    220 Increase, Plasma vitellogenin concentrations Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                    • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                    • ER agonism leading to reduced survival due to renal failure
                                                                                                                                                                                                                                                                                                                    1375 Increase, platelet aggregation Tissue Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                    • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                    1993 Increase, Pneumonia Organ Apr 7, 2022 Apr 7, 2022
                                                                                                                                                                                                                                                                                                                      1965 Increase, Pollen abnormal Organ Jan 13, 2022 Jan 13, 2022
                                                                                                                                                                                                                                                                                                                      • Deposition of ionising energy leads to population decline via pollen abnormal
                                                                                                                                                                                                                                                                                                                      623 Increase, predation Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                      1893 increase, Preeclampsia Individual May 31, 2021 May 31, 2021
                                                                                                                                                                                                                                                                                                                      • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                      1524 Increase, Premature molting Individual 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
                                                                                                                                                                                                                                                                                                                      774 Increase, Preneoplastic foci (hepatocytes) Cellular Nov 29, 2016 Sep 16, 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)
                                                                                                                                                                                                                                                                                                                      2097 Increase, Pro-Inflammatory Mediators Tissue Jan 25, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                      • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                      1864 Increase, Programmed cell death Cellular Apr 11, 2021 Apr 12, 2021
                                                                                                                                                                                                                                                                                                                      • Deposition of ionising energy leading to population decline via programmed cell death
                                                                                                                                                                                                                                                                                                                      1579 Increase, proinflammatory mediators (TNFalpha) Molecular Jan 7, 2019 Jan 7, 2019
                                                                                                                                                                                                                                                                                                                      • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                      923 Increase, Proliferation of goblet cells Cellular Nov 29, 2016 Aug 20, 2021
                                                                                                                                                                                                                                                                                                                        1767 Increase, Protein oxidation Molecular Apr 30, 2020 Apr 30, 2020
                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                        2077 Increase, pulmonate breathing Individual Nov 16, 2022 Nov 16, 2022
                                                                                                                                                                                                                                                                                                                        • Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
                                                                                                                                                                                                                                                                                                                        246 Increase, RBC congestion in liver Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                        1364 Increase, Reactive oxygen species Molecular Apr 15, 2017 Mar 19, 2019
                                                                                                                                                                                                                                                                                                                        • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                        • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                        • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                        257 Increase, Reactive Oxygen Species production Molecular Nov 29, 2016 Apr 11, 2021
                                                                                                                                                                                                                                                                                                                        • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (1)
                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (2)
                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                        • Excessive reactive oxygen species production leading to mortality (4)
                                                                                                                                                                                                                                                                                                                        • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to population decline via DNA oxidation and follicular atresia
                                                                                                                                                                                                                                                                                                                        • Increased reactive oxygen species production leading to decreased cognitive function
                                                                                                                                                                                                                                                                                                                        • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                        778 Increase, Regenerative cell proliferation (corneal cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                        781 Increase, Regenerative cell proliferation (forestomach epithelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
                                                                                                                                                                                                                                                                                                                        787 Increase, Regenerative cell proliferation (hepatocytes) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                        734 Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells) Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                        • Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
                                                                                                                                                                                                                                                                                                                        710 Increase, Regenerative cell proliferation (tubular epithelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                        • Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                        795 Increase, Regenerative cell proliferation (urothelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                        • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                        252 Increase, Renal pathology due to VTG deposition Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                        • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                        869 Increase, Respiratory or Squamous Metaplasia Tissue Nov 29, 2016 Sep 29, 2017
                                                                                                                                                                                                                                                                                                                        • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                        1652 Increase, S-adenosylmethionine depletion Molecular May 30, 2019 May 30, 2019
                                                                                                                                                                                                                                                                                                                          1348 Increase, seizure Individual Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                          • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                          • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                                                                                                                                                                                                                                                                                          • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                          1315 Increase, Selective Serotonin Reuptake Inhibitors (SSRIs) Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                            2049 Increase, sex ratio (F/M) Individual Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                            • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                            872 Increase, Site of Contact Nasal Tumors Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                            • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                            • Cytochrome oxidase inhibition leading to olfactory nasal lesions
                                                                                                                                                                                                                                                                                                                            2021 Increase, slincR expression Molecular Jun 29, 2022 Aug 1, 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
                                                                                                                                                                                                                                                                                                                            1525 Increase, Sulfonylurea receptor binding Molecular May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                            • S-adenosylmethionine depletion leading to population decline (2)
                                                                                                                                                                                                                                                                                                                            • Sulfonylureareceptor binding leading to mortality
                                                                                                                                                                                                                                                                                                                            1381 Increase, surfactant Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                            • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                            1748 Increase, the risk of acute respiratory failure Organ Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                            • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                            753 Increase, Thyroid-stimulating hormone (TSH) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                              868 Increase, Tissue Degeneration, Necrosis & Atrophy Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                              • Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
                                                                                                                                                                                                                                                                                                                              1809 Increase, Tissue/organ damage Organ Nov 2, 2020 Nov 2, 2020
                                                                                                                                                                                                                                                                                                                              • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                              1950 Increase, TNF Molecular Nov 18, 2021 Nov 18, 2021
                                                                                                                                                                                                                                                                                                                              • Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
                                                                                                                                                                                                                                                                                                                              1471 Increase, Uncoupling of photophosphorylation Cellular Oct 10, 2017 Oct 10, 2017
                                                                                                                                                                                                                                                                                                                              • Reduction in photophosphorylation leading to growth inhibition in aquatic plants
                                                                                                                                                                                                                                                                                                                              793 Increase, Urinary bladder calculi Organ Nov 29, 2016 Oct 26, 2017
                                                                                                                                                                                                                                                                                                                              • Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                              2161 Increase, Vascular disrupting effects Individual 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 HIF1α, Semaphorin 6A, and Dll4-Notch pathway
                                                                                                                                                                                                                                                                                                                              • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                              • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                              1342 Increase, vascular smooth muscle contraction Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                              • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                              • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                              2046 Increase, Vitellogenin mRNA Molecular Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                              • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                              307 Increase, Vitellogenin synthesis in liver Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                              • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                              1745 Increase,collagen synthesis Cellular Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                                1888 Increased (ectopic) all-trans retinoic acid concentration Tissue May 29, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                • Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
                                                                                                                                                                                                                                                                                                                                1948 Increased ACE2 expression Molecular Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                                                                                1172 Increased activation, Nuclear factor kappa B (NF-kB) Cellular Nov 29, 2016 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                1039 Increased activity, beta-2 adrenergic receptor Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                2128 Increased adipocyte numbers Cellular Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                2127 Increased adipocyte size Cellular Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                1449 increased adipogenesis Tissue Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                1852 Increased Ang II type 1 receptor (AT1R) Tissue Mar 30, 2021 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                1752 Increased Angiotensin II Cellular Mar 17, 2020 Apr 4, 2021
                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                • Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
                                                                                                                                                                                                                                                                                                                                1026 Increased Apoptosis, Adenomas/carcinomas (follicular cell) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                  496 Increased apoptosis, decreased fetal/adult Leydig Cells Cellular Nov 29, 2016 May 17, 2023
                                                                                                                                                                                                                                                                                                                                  • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                  • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                  1722 Increased blood CCK level Organ Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                  • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                  1663 Increased brain Homocysteine level Organ Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                    1433 Increased CGRP, neuronal release of CGRP Cellular Jun 23, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                    39 Increased Cholinergic Signaling Organ Nov 29, 2016 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                    • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                    • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                    • Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
                                                                                                                                                                                                                                                                                                                                    1723 Increased exocrine secretion from pancreatic acinar cells Cellular Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                    • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                    2125 Increased fat mass Organ Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                    1661 Increased Homocysteine level Cellular Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                    • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                    1929 Increased incidence of cardiovascular morbidity and mortality in the general population Population Aug 21, 2021 Aug 21, 2021
                                                                                                                                                                                                                                                                                                                                      1996 Increased incidence of digestive morbidity and mortality in the general population Population Apr 7, 2022 Apr 7, 2022
                                                                                                                                                                                                                                                                                                                                        2087 Increased incidence of respiratory disease Individual Jan 9, 2023 Jan 9, 2023
                                                                                                                                                                                                                                                                                                                                        • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                        1992 Increased incidence of respiratory morbidity and mortality in the general population Population Apr 7, 2022 Apr 7, 2022
                                                                                                                                                                                                                                                                                                                                          2183 Increased incidence of vascular calcification and atherosclerosis morbidity Population Sep 4, 2023 Nov 14, 2023
                                                                                                                                                                                                                                                                                                                                            1750 Increased inflammatory immune responses Tissue Mar 10, 2020 Jan 21, 2021
                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                            • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                                                                                            1721 Increased intestinal monitor peptide level Organ Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                            2149 Increased intracelluar Iron accumulation Cellular Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                            • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                            • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                            2148 Increased LCN2/iron complex binds to SLC22A17 receptor in neuron Molecular Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                            • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                            2130 increased lipid accumulation Cellular Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                            • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                            1256 increased mantel display Organ 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
                                                                                                                                                                                                                                                                                                                                            1980 Increased microRNA expression Cellular Mar 22, 2022 Aug 27, 2023
                                                                                                                                                                                                                                                                                                                                            • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                            2081 Increased Modified Proteins Molecular Dec 16, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                            2156 Increased morbidity of congenital heart defect Population Jul 31, 2023 Jul 31, 2023
                                                                                                                                                                                                                                                                                                                                              351 Increased Mortality Population Nov 29, 2016 Jul 8, 2022
                                                                                                                                                                                                                                                                                                                                              • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                              • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                              • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                              • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                              • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                              • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                              • Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​
                                                                                                                                                                                                                                                                                                                                              • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated 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
                                                                                                                                                                                                                                                                                                                                              • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                              • 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)
                                                                                                                                                                                                                                                                                                                                              • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                              • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                              • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                              1999 Increased mortality of neurodegenerative diseases Population Apr 7, 2022 Apr 7, 2022
                                                                                                                                                                                                                                                                                                                                                1897 increased MyD88 activation Molecular 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)
                                                                                                                                                                                                                                                                                                                                                1435 Increased neurokinin A (NKA) by neuronal cells Cellular Jun 23, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                1147 increased or inappropriate, mantel display Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                  1662 Increased plasma Homocysteine level Tissue Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                    1900 increased platelet surface TLR9 expression Cellular 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)
                                                                                                                                                                                                                                                                                                                                                    2132 Increased pro-inflammatory cytokine expression Cellular Apr 6, 2023 Apr 6, 2023
                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                    1493 Increased Pro-inflammatory mediators Tissue Nov 28, 2017 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                                                                                    • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                    • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                    1546 Increased reactive oxygen species (in the mitochondria) Cellular Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                    1898 increased release of danger/damage associated molecular patterns Tissue 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)
                                                                                                                                                                                                                                                                                                                                                    1226 Increased Respiratory irritability and Chronic Cough, Organ Nov 29, 2016 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                    1847 Increased SARS-CoV-2 production Cellular Mar 25, 2021 Jun 14, 2022
                                                                                                                                                                                                                                                                                                                                                    • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                    • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection leading to pyroptosis
                                                                                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                    • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                    1855 Increased Sodium-sensitive hypertension Tissue Apr 7, 2021 Apr 7, 2021
                                                                                                                                                                                                                                                                                                                                                    • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                    2033 Increased sphingolipid-1-phosphate Cellular Jul 19, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                    • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                    1460 Increased Substance P (SP) by goblet cells Cellular Jul 27, 2017 Jul 27, 2017
                                                                                                                                                                                                                                                                                                                                                      1441 Increased systemic total cholesterol pool Organ Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                        1858 Increased viral transcription and replication Cellular Apr 9, 2021 Apr 9, 2021
                                                                                                                                                                                                                                                                                                                                                          1030 Increased, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                            1326 Increased, 5-HT3 (5-hydroxytryptamine) Molecular Apr 13, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                            • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                            708 Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                            • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                            134 Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              2231 Increased, activation of renin, angiotensin, aldosterone system (RAAS) Cellular Jun 6, 2024 Jun 6, 2024
                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                              1499 Increased, activation of T (T) helper (h) type 2 cells Tissue Jan 3, 2018 May 12, 2023
                                                                                                                                                                                                                                                                                                                                                              • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                              1082 Increased, adenomas (pituitary) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                              1079 Increased, Adenomas/carcinomas (mammary) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                              1070 Increased, adenosquamous carcinomas of endometrium Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                              1029 Increased, adipogenesis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                              2230 Increased, afferent artery vasoconstriction Tissue Jun 6, 2024 Jun 18, 2024
                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                              1345 Increased, agitation Molecular Apr 13, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                              • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                              • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                              591 Increased, amputations Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                              1213 Increased, Angiogenesis Cellular Nov 29, 2016 Dec 20, 2022
                                                                                                                                                                                                                                                                                                                                                              • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                              880 Increased, ApoB100 Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                              574 Increased, Appetite and hunger Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                              • Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                              602 Increased, Ataxia, paralysis, or hyperactivity Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                              444 Increased, Atrioventricular block and bradycardia Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                              2124 increased, Bax expression Molecular Apr 4, 2023 Sep 7, 2023
                                                                                                                                                                                                                                                                                                                                                              • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                              714 Increased, Binding of chemicals to 2u (serum) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
                                                                                                                                                                                                                                                                                                                                                              1098 Increased, blood potassium concentration Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                              1096 Increased, blood uric acid concentration Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                              • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                              699 Increased, cardiac arrthymia Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Altered ion channel activity leading impaired heart function
                                                                                                                                                                                                                                                                                                                                                              863 Increased, Catabolism of Muscle Protein Organ Nov 29, 2016 Apr 30, 2019
                                                                                                                                                                                                                                                                                                                                                              • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                              1089 Increased, Cell Proliferation (mesothelium) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                              1062 Increased, Cellular proliferation / hyperplasia of acinar cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                              761 Increased, Chloride conductance Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                              • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                              • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                              • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                              1011 Increased, Chloride influx Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                1059 Increased, cholestasis Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                696 Increased, Chromosome misseggregation Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                1162 Increased, cilia movement Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                  1076 Increased, circulating estrogen levels Organ 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.
                                                                                                                                                                                                                                                                                                                                                                  • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                  961 Increased, Clearance of thyroxine from serum Tissue Nov 29, 2016 Jan 26, 2021
                                                                                                                                                                                                                                                                                                                                                                  • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                  • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                                                                                                                                  • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                  384 Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                    423 Increased, Clonal Expansion / Cell Proliferation to Form Pre-Neoplastic Altered Hepatic Foci Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                      693 Increased, cyclic adenosine monophosphate Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                      458 Increased, De Novo FA synthesis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                      • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                      1109 Increased, Deformed Wing Virus levels Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Varroa mite infestation increases virus levels leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                      1346 Increased, depression Individual Apr 13, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                      • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                      • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                      1001 Increased, Developmental Defects Molecular Nov 29, 2016 Aug 31, 2023
                                                                                                                                                                                                                                                                                                                                                                      • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                                      1790 Increased, Differentiation to Testis Tissue Jun 15, 2020 Dec 28, 2022
                                                                                                                                                                                                                                                                                                                                                                      • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor agonism leading to male-biased sex ratio
                                                                                                                                                                                                                                                                                                                                                                      323 Increased, Disease susceptibility Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                      1669 Increased, DNA damage and mutation Cellular Jul 3, 2019 Aug 13, 2019
                                                                                                                                                                                                                                                                                                                                                                      • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                      • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                      • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                      • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                      1281 Increased, DNA Damage-Repair Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                      • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                      1192 Increased, Ductal Hyperplasia Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                      1110 Increased, Energetic demands and therefore metabolic stress Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Nosema infection increases energetic demands leading to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                      1363 Increased, epilepsy Individual Apr 14, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                      • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                      • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                      • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                      1187 Increased, ER binding to DNA (classical pathway) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                      1188 Increased, ER binding to T.F. to DNA (non-classical pathway) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                      2205 Increased, essential element imbalance Molecular Jan 24, 2024 May 9, 2024
                                                                                                                                                                                                                                                                                                                                                                      • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                      748 Increased, Estrogen receptor (ER) activity Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                      • Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
                                                                                                                                                                                                                                                                                                                                                                      • Alcohol dehydrogenase leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                      1973 Increased, estrogens Cellular Feb 25, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                      • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                      • SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
                                                                                                                                                                                                                                                                                                                                                                      2199 Increased, Expression of LXR activated genes Molecular Dec 7, 2023 Mar 29, 2024
                                                                                                                                                                                                                                                                                                                                                                      • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                      1501 Increased, extracellular matrix deposition Tissue Jan 5, 2018 Jan 25, 2022
                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                      • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                      1320 Increased, extracellular serotonin Molecular Apr 13, 2017 May 31, 2017
                                                                                                                                                                                                                                                                                                                                                                      • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                      • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                      • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                      • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                      • SSRI (Selective serotonin reuptake inhibitor) to hypertension
                                                                                                                                                                                                                                                                                                                                                                      465 Increased, FA Influx Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                      • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                      • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                      460 Increased, Fatty acid uptake Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                        1500 Increased, fibroblast proliferation and myofibroblast differentiation Tissue Jan 5, 2018 May 17, 2023
                                                                                                                                                                                                                                                                                                                                                                        • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                        1035 Increased, Firbrosarcoma Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                        • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                        624 Increased, foot detachment Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                        959 Increased, Free serum thyroxine (T4) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                        • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                        2143 Increased, gene expression of AR Molecular May 18, 2023 May 18, 2023
                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                        421 Increased, glomerular rupture and renal hemorrhaging Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                        • ER agonism leading to reduced survival due to renal failure
                                                                                                                                                                                                                                                                                                                                                                        1396 Increased, glucocorticoid receptor activity Molecular May 31, 2017 May 31, 2017
                                                                                                                                                                                                                                                                                                                                                                        • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                        • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                        1350 Increased, glutamate Molecular Apr 14, 2017 Oct 11, 2021
                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                        • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                        • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                        2079 Increased, glycolipid levels Cellular Dec 13, 2022 May 17, 2023
                                                                                                                                                                                                                                                                                                                                                                        • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                                                        1037 Increased, hemagiosarcoma Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                        • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                        1158 Increased, Hepatic thyroid hormone uptake/transport Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                        • AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
                                                                                                                                                                                                                                                                                                                                                                        802 Increased, HIF-1 alpha transcription Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                        • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                        799 Increased, HIF-1 heterodimer Cellular 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
                                                                                                                                                                                                                                                                                                                                                                        1362 Increased, hippocampal hyperdepolarization Molecular Apr 14, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                        2206 Increased, histomorphological alteration of testis Tissue Jan 24, 2024 Apr 10, 2024
                                                                                                                                                                                                                                                                                                                                                                        • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                        1025 Increased, Hyperplasia (follicular cells) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                          1069 Increased, Hyperplasia (glandular epithelial cells of endometrium) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                          • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                          1085 Increased, hyperplasia (mammary gland) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                          • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                          1024 Increased, Hypertrophy and proliferation (follicular cell) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                            1034 Increased, IGF-1 (mouse) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                            • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                            376 Increased, Induced Mutations in Critical Genes Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                            • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                            726 Increased, Induction of pyruvate dehydrogenase (PDH) Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                            1020 Increased, induction of UDPGT's in liver Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                              1087 Increased, inflammation Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                              • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                              1012 Increased, Inhibitory postsynaptic potential Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                              • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                              • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                              • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                              493 Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                              • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                              1933 Increased, Interleukin-6 production Cellular Sep 20, 2021 Sep 20, 2021
                                                                                                                                                                                                                                                                                                                                                                              • Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                              389 Increased, Intracellular Calcium overload Cellular Nov 29, 2016 Jun 26, 2020
                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                              1322 Increased, intracellular chloride (Cl-) Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                              • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                              • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                              1398 Increased, intracellular serotonin Cellular Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                              • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                              1321 Increased, intracellular sodium (Na+) Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                              • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                              • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                              • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                              1196 Increased, Invasion Cellular Nov 29, 2016 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                                                                              • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                              • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                              • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                              759 Increased, Kidney Failure Organ Nov 29, 2016 Jun 18, 2024
                                                                                                                                                                                                                                                                                                                                                                              • Kidney toxicity induced by activation of 5HT2C
                                                                                                                                                                                                                                                                                                                                                                              • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                              • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                              • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                              1985 Increased, Kisspeptin signalling Molecular Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                              • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                              1081 Increased, lactotroph hyperplasia and hypertrophy Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                              • GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                              1080 Increased, latency period Individual 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
                                                                                                                                                                                                                                                                                                                                                                              467 Increased, LDL uptake Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                              342 Increased, Lethality Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                1411 Increased, leukocyte activation Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                1410 Increased, leukocyte adherence Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                791 Increased, Leutinizing hormone (LH) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                1445 Increased, Lipid peroxidation Molecular Jun 29, 2017 Jul 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                • Excessive reactive oxygen species production leading to mortality (3)
                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                1306 Increased, lipogenesis Molecular Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                  1036 Increased, liposarcoma Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                  • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                  459 Increased, Liver Steatosis Organ Nov 29, 2016 May 21, 2024
                                                                                                                                                                                                                                                                                                                                                                                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • AKT2 activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                  • Glucocorticoid Receptor activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                  622 Increased, locomotion Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                  • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                  754 Increased, Luteinizing hormone (LH) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                  • Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                  1791 Increased, Male Biased Sex Ratio Population 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
                                                                                                                                                                                                                                                                                                                                                                                  1208 Increased, Male offspring Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                  • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                  1160 Increased, mantel display Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    1090 Increased, mesotheliomas Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                    • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                    1190 Increased, Migration (Endothelial Cells) Cellular Nov 29, 2016 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                    • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                    1241 Increased, Motility Cellular Nov 29, 2016 Feb 28, 2024
                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                    • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                    625 Increased, muscular waves in foot Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                    422 Increased, nephropathy Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • ER agonism leading to reduced survival due to renal failure
                                                                                                                                                                                                                                                                                                                                                                                    1015 Increased, Neuronal synaptic inhibition Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                    • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                    1191 Increased, Non-genomic signaling Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                    1491 Increased, Oncotic Necrosis Tissue Nov 14, 2017 Nov 27, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                    1990 Increased, Oocyte Atresia Tissue Apr 5, 2022 Apr 5, 2022
                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
                                                                                                                                                                                                                                                                                                                                                                                    1161 Increased, oocyte maturation Organ Nov 29, 2016 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                    356 Increased, Oxidative damage Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                    1088 Increased, Oxidative Stress Molecular Nov 29, 2016 Feb 3, 2022
                                                                                                                                                                                                                                                                                                                                                                                    • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                    • 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
                                                                                                                                                                                                                                                                                                                                                                                    • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                    • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                    • Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                    • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                                                                    • Increased reactive oxygen species production leading to decreased cognitive function
                                                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                    1399 Increased, packaged serotonin Cellular Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                    1063 Increased, Pancreatic acinar tumors Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                    1665 Increased, Plasma HCY level Tissue Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                    775 Increased, Plasma tyrosine Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                    1164 Increased, Population 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
                                                                                                                                                                                                                                                                                                                                                                                    1057 Increased, PPAR-alpha activation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                    • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                    588 Increased, predation Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                    • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                                                    • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                    • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                    • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
                                                                                                                                                                                                                                                                                                                                                                                    • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                    1577 Increased, proinflammatory mediators (TNFalpha) Molecular Jan 7, 2019 Jan 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                      1077 Increased, prolactin exposure Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                      • GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
                                                                                                                                                                                                                                                                                                                                                                                      1084 Increased, prolactin secretion Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                      • Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
                                                                                                                                                                                                                                                                                                                                                                                      1189 Increased, Proliferation (Endothelial cells) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                      1033 Increased, proliferation of mesenchymal cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                      • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                      377 Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered Hepatic Foci (AHF)) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                        1357 Increased, RDX dose Molecular Apr 14, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                        • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                        • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                        1922 Increased, Reactive metabolites production Cellular Aug 19, 2021 Aug 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                        1115 Increased, Reactive oxygen species Cellular Nov 29, 2016 Apr 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                        • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                        • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                        • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                        • Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leads to population decline via impaired meiosis
                                                                                                                                                                                                                                                                                                                                                                                        • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                        • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                        • Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of ionising energy leading to population decline via mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                        • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                        • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                        • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                                                                        • Glutathione conjugation leading to reproductive dysfunction via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                        • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                        • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                        • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                        1497 Increased, recruitment of inflammatory cells Tissue Jan 3, 2018 May 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                        • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                        • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                        • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                        • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                        • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                        • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                        • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                        • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                        • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                        1031 Increased, release of growth factors Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                          419 Increased, renal vitellogenin deposition Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                          • ER agonism leading to reduced survival due to renal failure
                                                                                                                                                                                                                                                                                                                                                                                          1163 Increased, Reproductive Success Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                          • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                          1159 Increased, reuptake of 5-HT (5-hydroxytryptamine transporter; sodium-dependent serotonin transporter Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                            1242 Increased, Second Messenger Production Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                            • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                            1049 Increased, secrection of FSH from anterior pituitary Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                            • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                            2004 Increased, secretion of catecholamine Cellular Apr 22, 2022 Apr 22, 2022
                                                                                                                                                                                                                                                                                                                                                                                              1047 Increased, secretion of GnRH from hypothalamus Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                                              1048 Increased, secretion of leutenizing hormone Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                1050 Increased, secretion of LH from anterior pituitary Cellular 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
                                                                                                                                                                                                                                                                                                                                                                                                1032 Increased, secretion of local growth factors Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                • PPARgamma activation leading to sarcomas in rats, mice, and hamsters
                                                                                                                                                                                                                                                                                                                                                                                                • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                1496 Increased, secretion of proinflammatory mediators Cellular Jan 2, 2018 May 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                • Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis leads to malignant mesothelioma
                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                • Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
                                                                                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                • Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                1344 Increased, seizure Individual Apr 13, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                626 Increased, serotonin (5-HT) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                                620 Increased, serotonin (5-HT) 1 1 Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                  1397 Increased, serotonin transporter activity Cellular Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                  • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                  813 Increased, Serum creatinine Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                  • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                  2122 increased, socio-economic burden Population Apr 4, 2023 Feb 5, 2024
                                                                                                                                                                                                                                                                                                                                                                                                  • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                  1972 Increased, Steroidogenic acute regulatory protein (StAR) Cellular Feb 25, 2022 Mar 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                  • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                  366 Increased, Structural malformations Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                    1400 Increased, synaptic release Cellular Jun 1, 2017 Jun 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to seizure
                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to depression
                                                                                                                                                                                                                                                                                                                                                                                                    • Serotonin transporter activation to agitation
                                                                                                                                                                                                                                                                                                                                                                                                    1021 Increased, T4/T3 catabolism Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      1023 Increased, Thyroid-stimulating hormone (TSH) Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                      • 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)
                                                                                                                                                                                                                                                                                                                                                                                                      1828 Increased, Thyroxine (T4) in serum Organ Dec 9, 2020 Dec 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                      • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                      881 Increased, Triglyceride Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                      454 Increased, Triglyceride formation Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                      • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                      1154 Increased, Triiodothyronine (T3) in tissues Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                      • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                      1971 Increased, tumor growth Organ Feb 15, 2022 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                      960 Increased, Uptake of thyroxine into tissue Cellular Nov 29, 2016 Dec 17, 2016
                                                                                                                                                                                                                                                                                                                                                                                                      • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                      1142 Increased, valve movement Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                      • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                      576 Increased, Viral susceptibility Individual 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
                                                                                                                                                                                                                                                                                                                                                                                                      418 Increased, Vitellogenin synthesis Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                      • ER agonism leading to reduced survival due to renal failure
                                                                                                                                                                                                                                                                                                                                                                                                      1166 Increased, water pumping Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                        1139 Increased, water retention in foot Organ Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                        1919 Increased,Cardiac Dysregulation Tissue Aug 18, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                          1924 Increased,Cardiac fibrosis Organ Aug 19, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                            1918 Increased,Myocardial apoptosis Cellular Aug 18, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                              1926 Increased,Vascular fibrosis Tissue Aug 19, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                1927 Increased,Vascular endothelial cell autophagy dysfunction Cellular Aug 19, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                  1928 increased,Vascular endothelial dysfunction Tissue Aug 19, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                                                                                                                                                                                  • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                  • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                  • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                  1925 Increased,Vascular smooth muscle cell activation Cellular Aug 19, 2021 Sep 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                    1940 Increases in cellular reactive oxygen species Molecular Oct 25, 2021 May 10, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                    • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                    1455 Incudtion, Sustained inflammatory cytokine release Molecular Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                      1664 Induce Neuronal dysfunctions Individual Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                        1740 Induced dysregulation of ACE2 Molecular Mar 10, 2020 Mar 3, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                        1257 Induced parturition Individual 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
                                                                                                                                                                                                                                                                                                                                                                                                                        1255 induced spawning Individual Jan 13, 2017 Jan 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                        • 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
                                                                                                                                                                                                                                                                                                                                                                                                                        1741 Induced, Angiotensin (Ang) II accumulation Tissue Mar 10, 2020 Mar 30, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                        • ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
                                                                                                                                                                                                                                                                                                                                                                                                                        1666 Induced, dysfunction of microcirculation Organ Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                        • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                                                                                                                                                                        1167 induced, parturition Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                          1746 Induction lung fibrosis Organ Mar 10, 2020 Mar 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                            1711 Induction of GATA3 expression Cellular Dec 29, 2019 Aug 14, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
                                                                                                                                                                                                                                                                                                                                                                                                                            1959 Induction of hERG trafficking defects Cellular Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                              1459 Induction, Cell damage sensing Molecular Jul 26, 2017 Jul 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                60 Induction, Chitin degradation and resorption Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                  850 Induction, CYP1A2/CYP1A5 Molecular Nov 29, 2016 May 30, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                  1206 Induction, Doublesex1 gene Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                  145 Induction, IKB inhibitory protein Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                                                                                  164 Induction, Liver “Dysfunctional” Changes by CGA 330050 Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                  1209 Induction, Male reproductive tract Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                  • Juvenile hormone receptor agonism leading to male offspring induction associated population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                  1207 Induction, Male traits formation in embryos Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    838 Induction, Microvesicular fat Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                    1394 Induction, persistent proliferation/sustained proliferation Cellular May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                    1019 Induction, pharyngeal muscle paralysis Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                    • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                    238 Induction, Pre-mature molting Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                      1014 Induction, Somatic muscle paralysis Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                      269 Induction, Sustained Cell Proliferation Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                      270 Induction, Sustained Hepatotoxicity Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                      295 Induction, Upregulation of glucuronyltransferase activity Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                      1254 Infant leukaemia Individual Dec 16, 2016 Aug 1, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibitor binding to topoisomerase II leading to infant leukaemia
                                                                                                                                                                                                                                                                                                                                                                                                                                      901 Infiltration, Inflammatory cells Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                        907 Infiltration, Inflammatory cytokines Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                          1599 Inflamatory events in light-exposed tissues Organ Feb 3, 2019 Jul 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                          902 Inflammation, Liver Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                          2158 Influenza A Virus (IAV) binds sialic acid glycan receptor Molecular Jul 31, 2023 Aug 2, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                          2193 Influenza A Virus (IAV) budding Cellular Oct 2, 2023 Jan 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                          2159 Influenza A virus (IAV) cell entry Cellular Aug 11, 2023 Oct 3, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                          2194 Influenza A Virus (IAV) shedding and transmission Individual Oct 2, 2023 Oct 2, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                          2192 Influenza A Virus production increased Molecular Oct 2, 2023 Jan 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                          1216 Influx of Ca2+, Excitation of trigeminal nerves Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                            1470 inherited mutations in offspring Individual Aug 20, 2017 Aug 20, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                              1331 Inhibit, agitation Individual Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                1332 Inhibit, depression Individual Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                  1367 Inhibit, gastric ulcer formation Organ Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                  1316 Inhibit, serotonin transporter activity Molecular Apr 13, 2017 Apr 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                  2039 Inhibition GABAA receptor Molecular Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                  1799 Inhibition of 11β-HSD Molecular Jul 13, 2020 Jul 13, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
                                                                                                                                                                                                                                                                                                                                                                                                                                                  1880 Inhibition of ALDH1A (RALDH) Molecular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                  59 Inhibition of Apoptosis in Altered Hepatic Foci, Changes in Cellular Growth Homeostasis Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                    964 Inhibition of Aromatase Enzyme, Chemical exposure during critical window of estrous cycle between diestrus 2 and proestrus inhibits aromatase conversion of testosterone to estradiol Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                                                                                                                                                                                                                                                                                                                    1660 Inhibition of betaine-homocysteine methyltransferase Molecular Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                      2023 Inhibition of Ceramide Synthase Molecular Jul 14, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                      1887 Inhibition of CYP26B1 activity Molecular May 28, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                        1657 Inhibition of cystathionine beta-synthase Molecular Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
                                                                                                                                                                                                                                                                                                                                                                                                                                                        2235 inhibition of E4 (Uracil-DNA Glycosylase) Molecular Jun 10, 2024 Jun 10, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                        • C6R-Derived Protein K7 following Monkeypox infection leads to heart failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                        1884 Inhibition of Fyna Molecular May 28, 2021 Dec 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                        1960 Inhibition of Ikr Tissue Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                          1715 Inhibition of JAK3 Molecular Jan 5, 2020 Feb 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                          1672 Inhibition of lung surfactant function Molecular Jul 3, 2019 Oct 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                          1463 Inhibition of lysyl oxidase Cellular Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                          1658 Inhibition of Methionine synthase Molecular Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                            1659 Inhibition of Methylenetetrahydrofolate reductase Molecular Jun 14, 2019 Jun 14, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1481 Inhibition of mitochondrial DNA polymerase gamma (Pol gamma) Molecular Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1604 Inhibition of N-linked glycosylation Molecular Mar 6, 2019 Mar 6, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1429 Inhibition of N-type Ca ion channels Cellular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1430 Inhibition of neurotransmitter vesicle release Cellular Jun 23, 2017 Jun 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1885 Inhibition of Plxna2 Molecular May 28, 2021 Oct 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                              2100 Inhibition of rapid delayed rectifying potassium current Cellular Jan 29, 2023 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                              2155 Inhibition of Sulfotransferase E1 (SULT1E1) Molecular Jul 28, 2023 Aug 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                              • SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
                                                                                                                                                                                                                                                                                                                                                                                                                                                              2191 Inhibition of the Wnt/β-catenin pathway Cellular Sep 18, 2023 Sep 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1627 Inhibition of tyrosinase Molecular May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                2174 Inhibition VEGF/VEGFR pathway Cellular Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                766 Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                619 Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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 inhibition leading to decreased reproductive success and population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1617 Inhibition, 5α-reductase Molecular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                790 Inhibition, 5α-reductase activity Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1760 Inhibition, Activin signaling Cellular Apr 21, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                849 Inhibition, Antgonism of NE receptor Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                36 Inhibition, Aromatase Molecular Nov 29, 2016 Mar 14, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aromatase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                41 Inhibition, Bile Salt Export Pump (ABCB11) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                51 Inhibition, Ca++ ATPase Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Calcium-mediated neuronal ROS production and energy imbalance
                                                                                                                                                                                                                                                                                                                                                                                                                                                                980 Inhibition, Calcineurin Activity Molecular Nov 29, 2016 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1522 Inhibition, Chitin synthase 1 Molecular May 24, 2018 Feb 24, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • S-adenosylmethionine depletion leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chitin synthase 1 inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1806 Inhibition, Chitinase Molecular Oct 21, 2020 Sep 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chitinase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1807 Inhibition, Chitobiase Molecular Oct 21, 2020 Sep 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chitobiase inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                2232 Inhibition, COX-2 activity Molecular Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1103 Inhibition, Cyclooxygenase 1 activity Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                79 Inhibition, Cyclooxygenase activity Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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 spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1840 Inhibition, cytochrome oxidase Molecular Feb 19, 2021 Feb 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cytochrome oxidase inhibition leading to olfactory nasal lesions
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1609 Inhibition, Cytochrome P450 enzyme (CYP17A1) activity Molecular 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1009 Inhibition, Deiodinase 1 Molecular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1002 Inhibition, Deiodinase 2 Molecular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1153 Inhibition, Deiodinase 3 Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1156 Inhibition, Dual oxidase Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                2207 inhibition, EKR1/2 signaling pathway Cellular Jan 25, 2024 Jan 25, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                593 Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1490 Inhibition, Fatty Acid Beta Oxidation Molecular Nov 13, 2017 Nov 27, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                2065 Inhibition, Fatty acid oxidation Cellular Sep 19, 2022 Sep 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • PM2.5-related AOP frameworks on liver diseases
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1016 Inhibition, Feeding Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1761 Inhibition, Fin regeneration Tissue Apr 21, 2020 Jul 10, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                471 Inhibition, FoxA2 Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                804 Inhibition, HMG-CoA reductase Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1574 Inhibition, IKK complex Molecular Jan 7, 2019 Jan 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                147 Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307 Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                526 Inhibition, Inhibition of Dopamine-beta-hydroxylase Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1152 Inhibition, Iodotyrosine deiodinase (IYD) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                1308 Inhibition, LRH-1 Molecular Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1307 Inhibition, LXR Molecular Apr 12, 2017 Apr 12, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    105 Inhibition, Mitochondrial Electron Transport Chain Complexes Molecular Nov 29, 2016 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    451 Inhibition, Mitochondrial fatty acid beta-oxidation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1013 Inhibition, Motor neuron activity Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      424 Inhibition, Na+/I- symporter (NIS) Molecular Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      887 Inhibition, NADH-ubiquinone oxidoreductase (complex I) Cellular Nov 29, 2016 Mar 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2233 Inhibition, NFAT Molecular Jun 7, 2024 Jun 7, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Calcineurin leads to Kidney Failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      195 Inhibition, NMDARs Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen antagonism leading to increased risk of autism-like behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      202 Inhibition, Nuclear factor kappa B (NF-kB) Molecular Nov 29, 2016 Mar 2, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      877 Inhibition, organic anion transporter 1 (OAT1) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1155 Inhibition, Pendrin Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Pendrin inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      828 Inhibition, Phospholipase A Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      468 Inhibition, PPAR alpha Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      798 Inhibition, Prolyl hydroxylases Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1368 Inhibition, PTGS-1 (Prostaglandin-endoperoxide synthase 1) Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1371 Inhibition, PTGS-2 (Prostaglandin-endoperoxide synthase 2) Molecular Apr 17, 2017 Apr 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Gastric ulcer formation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      724 Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      584 Inhibition, sodium channel Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • sodium channel inhibition leading to increased predation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Sodium channel (Nav1.1) inhibition leading to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      878 Inhibition, SREBP1c Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • NFE2L2/FXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1680 Inhibition, TBX1 Molecular Aug 13, 2019 Aug 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • TBX1 inhibition leading to congenital cardiac conotruncal anomalies
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      845 Inhibition, UROD Molecular Nov 29, 2016 May 30, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      305 Inhibition, VegfR2 Molecular Nov 29, 2016 Jan 17, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1294 Inhibition, Wnt pathway Cellular Feb 15, 2017 Sep 16, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2037 Inositol triphosphate receptor activation Molecular Jul 25, 2022 Jul 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      298 Insufficiency, Vascular Molecular Nov 29, 2016 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2119 Insulin resistance, increased Individual Apr 3, 2023 May 26, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PM2.5-related AOP frameworks on liver diseases
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1584 Interaction of α-diketones with arginine residues Molecular Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      979 Interference, nuclear localization of NFAT Molecular Nov 29, 2016 Jul 2, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1901 Interferon-I antiviral response, antagonized by SARS-CoV-2 Cellular Jul 9, 2021 Dec 15, 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1074 interruption, Ovulation Individual 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.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1931 Intestinal barrier, disruption Organ Sep 1, 2021 Jun 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2014 Intestinal epithelial cell apoptosis Cellular Jun 6, 2022 Jun 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2015 Intestinal inflammation Organ Jun 6, 2022 Jun 6, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          405 irregularities, ovarian cycle Individual Nov 29, 2016 Nov 29, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1134 Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1117 Irreversible inhibition of VKOR by binding at tyrosine 139, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1118 Irreversible inhibition of VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1434 Irritation of nasal mucosa inducing sneeze reflex Tissue Jun 23, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              927 KE1 : S-Glutathionylation, eNOS Molecular Nov 29, 2016 Nov 20, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              935 KE2 : Decrease, GTPCH-1 Cellular Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              934 KE3 : Decrease, Tetrahydrobiopterin Cellular Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              932 KE4 : Uncoupling, eNOS Cellular Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              973 KE5 : Decrease, AKT/eNOS activity Cellular Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              933 KE6 : Depletion, Nitric Oxide Cellular Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              937 KE7 : Impaired, Vasodilation Organ Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              951 KE8 : Increase, Vascular Resistance Organ Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1795 Latent Transforming growth Factor beta expression Cellular Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1494 Leukocyte recruitment/activation Cellular Nov 28, 2017 Dec 1, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1511 Lipid Peroxidation Molecular Apr 4, 2018 Apr 4, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1395 Liver Cancer Organ May 30, 2017 Jun 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2034 liver dysfunction Organ Jul 20, 2022 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • The AOP framwork on silica nanopariticles induced hepatoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1549 Liver Injury Organ Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1389 Locomotor activity, decreased Individual May 2, 2017 May 18, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1498 Loss of alveolar capillary membrane integrity Tissue Jan 3, 2018 May 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1675 Loss of barrier function Tissue Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2078 Loss of drebrin Cellular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                319 Loss, Cochlear function Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1670 Lung cancer Organ Jul 3, 2019 Aug 13, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1276 Lung fibrosis Organ Feb 15, 2017 Dec 26, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding to ACE2 leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1246 Lung function, Decrease Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1540 lysosomal disruption EMPTY Molecular Nov 12, 2018 Apr 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1616 Malformation, cryptorchidism - maldescended testis Organ Apr 10, 2019 Apr 18, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor antagonism leading to testicular cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    348 Malformation, Male reproductive tract Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    809 malformed, Male reproductive tract Individual Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • HMG-CoA reductase inhibition leading to decreased fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1822 Maturation of TNF/iNOS-Producing Dendritic Cells Cellular Nov 23, 2020 Nov 23, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1941 Memory Loss Individual 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2145 Metabolic syndrome Population 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2129 Metabolically unhealthy Obesity Individual Apr 5, 2023 Apr 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    409 Metabolism of AFB1, Production of Reactive Electrophiles Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    987 Metaplasia of goblet cells Molecular Nov 29, 2016 Oct 5, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1982 metastatic breast cancer Organ Mar 22, 2022 May 14, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • DNA damage and mutations leading to Metastatic Breast Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of the AhR leading to metastatic breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2211 Microcephaly Organ Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1541 Mitochondrial Complex I inhibition Molecular Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1543 Mitochondrial Complex IV inhibition Molecular Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1544 Mitochondrial Complex V inhibition Molecular Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          177 Mitochondrial dysfunction Cellular Nov 29, 2016 Apr 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thermal stress leading to population decline (3)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thermal stress leading to population decline (2)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Thermal stress leading to population decline (1)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 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 DNA polymerase gamma leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Renal protein alkylation leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Immune mediated hepatitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Endocytotic lysosomal uptake leads to intestinal barrier disruption
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1816 Mitochondrial dysfunction EMPTY Cellular Nov 2, 2020 Apr 17, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1547 Mitochondrial Injury Cellular Dec 19, 2018 Dec 19, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1195 modulation, Extracellular Matrix Composition Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Estrogen receptor activation leading to breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          598 modulation, sodium channel Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          801 modulation, Unknown Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1912 Motile Cilia Number/Length, Decreased Cellular Jul 23, 2021 Sep 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1425 Mu Opioid Receptor Agonism Molecular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1909 Mucociliary Clearance, Decreased Individual Jul 19, 2021 Sep 10, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1245 Mucus , Hypersecretion Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1244 Mucus hypersecretion, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1910 Mucus Viscosity, Increased Organ Jul 19, 2021 Sep 9, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1843 Multi Organ Failure involving Acute Respiratory Distress Syndrome Individual Mar 19, 2021 Nov 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1934 Myocardial Infarction Organ Oct 15, 2021 Oct 15, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                312 N/A, Allergic contact dermatitis on challenge Individual Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  27 N/A, Androgen receptor, Antagonism Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  764 N/A, Ataxia, paralysis, or hyperactivity Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Glutamate-gated chloride channel activation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1193 N/A, Breast Cancer Individual Nov 29, 2016 Feb 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  75 N/A, Covalent binding to protein, possibly lysine residue Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    321 N/A, Cyanosis occurs Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    119 N/A, Gap Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    139 N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects Tissue Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Sustained AhR Activation leading to Rodent Liver Tumours
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    590 N/A, hypoxia Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    337 N/A, Impairment of reproductive capacity Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    158 N/A, Interferences with SH-/selen-proteins Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      344 N/A, Liver fibrosis Organ Nov 29, 2016 Dec 5, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Protein Alkylation leading to Liver Fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endocytic lysosomal uptake leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      345 N/A, Liver Steatosis Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      173 N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      352 N/A, Neurodegeneration Tissue Nov 29, 2016 Feb 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      213 N/A, Parent compound is converted to the reactive metabolite and forms free radicals leading to oxidation of heme iron(II) in hemoglobin to iron(III) Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      253 N/A, Reproductive failure Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      634 N/A, sedation Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Histamine (H2) receptor antagonism leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1489 N/A, Steatohepatisis Organ Nov 13, 2017 Nov 27, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      294 N/A, Unknown Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Kidney toxicity induced by activation of 5HT2C
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1259 narcosis Cellular Feb 7, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1263 Necrosis Tissue Feb 7, 2017 Feb 7, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AOP from chemical insult to cell death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1548 Necrotic Tissue Tissue Dec 19, 2018 Mar 7, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Mitochondrial complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • IKK complex inhibition leading to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1557 Neural crest cell migration, reduced Cellular Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Histone deacetylase inhibition leads to impeded craniofacial development
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1561 Neural tube defects Tissue Dec 20, 2018 Dec 20, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Histone deacetylase inhibition leads to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1514 Neurodegeneration Organ Apr 4, 2018 Apr 4, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1436 neurogenic inflammation of sensory nerves Cellular Jun 27, 2017 Jun 27, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        188 Neuroinflammation Tissue 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 agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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 Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2150 Neurological disorder Individual Jun 15, 2023 Jun 15, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        191 Neuronal dysfunction Cellular Nov 29, 2016 Apr 7, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Increased LCN2/iron complex leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1915 Neutrophil activation, Increased Cellular Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1417 NFE2/Nrf2 repression Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1786 Nipple retention (NR), increased Individual May 11, 2020 Jan 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1895 NLRP3 inflammasome activity, increased Molecular Jun 25, 2021 Jun 25, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • SARS-CoV-2 infection leading to pyroptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2019 Non-alcoholic fatty liver disease Individual Jun 27, 2022 Jun 27, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PM2.5-related AOP frameworks on liver diseases
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2007 Non-coding RNA expression profile alteration Molecular May 31, 2022 May 31, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1235 Non-neuronal production of IL-8/CXCL1, Epithelial irritation Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1224 Non-neuronal production of TNF, Epithelial irritation Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            862 Not Increased, Circulating Ketone Bodies Tissue Nov 29, 2016 Apr 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1466 Notochord distortion or malformations Organ Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1447 obesity Individual Jul 24, 2017 Jul 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2083 Occurrence of Cataracts Organ Dec 18, 2022 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2096 Occurrence, (Micro)vascular dysfunction Tissue Jan 23, 2023 Jul 31, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            616 Occurrence, A paroxysmal depolarizing shift Tissue Nov 29, 2016 Apr 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            835 Occurrence, Ballooning degeneration (hepatocyte) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2091 Occurrence, Bone Loss Organ Jan 11, 2023 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1106 Occurrence, cardiac arrhythmia Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1100 Occurrence, cardiac arrthymia Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              823 Occurrence, Cystic dilatation (renal tubule) Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              836 Occurrence, Cytoplasmic vacuolization (Bile duct cell) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              833 Occurrence, Cytoplasmic vacuolization (hepatocyte) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              837 Occurrence, Cytoplasmic vacuolization (kupffer cell) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              824 Occurrence, Cytoplasmic vacuolization (podocyte) Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              818 Occurrence, Cytoplasmic vacuolization (Renal tubule) Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              613 Occurrence, Epileptic seizure Individual Nov 29, 2016 Apr 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1623 Occurrence, Focal Seizure Tissue Apr 22, 2019 May 20, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              921 Occurrence, Hyperplasia of goblet cells Tissue Nov 29, 2016 Sep 21, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                814 Occurrence, Kidney toxicity Organ Nov 29, 2016 Mar 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                920 Occurrence, Metaplasia of goblet cells Tissue Nov 29, 2016 Aug 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1105 Occurrence, renal ischemia Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1097 Occurrence, renal proximal tubular necrosis Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1102 Occurrence, tophi (urate) deposition Tissue 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  919 Occurrence, Transdifferentiation of ciliated epithelial cells Cellular Nov 29, 2016 Aug 17, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2069 Occurrence, Vascular Remodeling Organ Oct 17, 2022 Mar 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1872 Olfactory epithelium degeneration Tissue Apr 25, 2021 Mar 30, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1871 olfactory sensory neurons, decrease Cellular Apr 25, 2021 Mar 30, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1218 Opening of calcium channel, Calcium influx Cellular Nov 29, 2016 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1427 Opening of G protein gated inward rectifying K channels Cellular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2187 Opening, voltage-gated calcium channels Molecular Sep 14, 2023 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2042 Orofacial clefting Individual Jul 27, 2022 May 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Antagonism of Smoothened receptor leading to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decrease, GLI1/2 target gene expression leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Decrease, cholesterol synthesis leads to orofacial clefting
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1151 Osteoporosis and vascular calcification, Bone deterioration Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    601 Overactivation, muscle contraction Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    600 Overactivation, Neuronotransmitter release Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    388 Overactivation, NMDARs Cellular Nov 29, 2016 Jan 4, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1886 Overexpression of rasl11b Molecular May 28, 2021 Dec 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    664 Overwhelmed, Mitochondrial DNA repair mechanisms Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    971 Ovulation of oocytes Reduced, Delayed, or Blocked, Decrease or delay in LH surge required for ovulation Individual Nov 29, 2016 May 19, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1596 Oxidation of DNA Cellular Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1594 Oxidation of membrane lipids Cellular Feb 3, 2019 Jul 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      926 Oxidation, Glutathione (To be considered with MIE) Molecular Nov 29, 2016 Nov 9, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      844 Oxidation, Uroporphyrinogen Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1595 Oxidation/denatuation of membrane proteins Cellular Feb 3, 2019 Jul 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1520 Oxidative phosphorylation Cellular May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1392 Oxidative Stress Molecular May 30, 2017 Mar 8, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyp2E1 Activation Leading to Liver Cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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 electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leads to vascular remodeling
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of cataracts
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of energy leading to occurrence of bone loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Essential element imbalance leads to reproductive failure via oxidative stress
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • CYP450 upregulation leads to Chronic kidney disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1510 Oxidative Stress in Brain Molecular Apr 4, 2018 Apr 4, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Excessive iron accumulation leading to neurological disorders
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1231 Oxidization of biomolecules, Lipid bilayer and cellular proteins Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1504 p21 (CDKN1A) expression, increase Cellular Jan 21, 2018 Nov 26, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1725 Pancreatic acinar cell tumors Molecular Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            896 Parkinsonian motor deficits Individual Nov 29, 2016 Mar 12, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            209 Peptide Oxidation Molecular Nov 29, 2016 Nov 13, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Peptide Oxidation Leading to Hypertension
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1947 Pericyte dysfunction Cellular Oct 28, 2021 Oct 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2095 Periventricular heterotopia formation Individual Jan 19, 2023 Jan 19, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            228 peroxisome proliferator activated receptor promoter demethylation Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Epigenetic modification of PPARG leading to adipogenesis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Demethylation of PPAR promotor leading to vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1086 persistent, cytotoxicity (pleura or peritoneum) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1289 Perturbation of cholesterol Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2182 Phenotype switching of vascular smooth muscle cells Cellular Sep 4, 2023 Sep 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1518 Photosynthesis, Decrease Cellular May 24, 2018 May 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1091 Physical and/or chemical interaction with cellular components, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1794 Pin-1 activation Cellular Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1639 Plasma RA level decreased Tissue May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1914 Platelet activation, Increased Cellular Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1857 Platelet-neutrophil interactions, Increased Cellular Apr 8, 2021 Apr 8, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1754 Porcupine-induced Wnt secretion and Wnt signaling activation Cellular Mar 23, 2020 Nov 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1979 Premature cell differentiation Organ Mar 21, 2022 Mar 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1889 Premature initiation of meiosis in fetal male germ cells Cellular May 29, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1146 premature, Spawning Individual Nov 29, 2016 Jan 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1144 premature, spawning 1 1 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1064 prepubertal increase, Estrogen receptor (ER) activity Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1232 Production of nerve growth factor , Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1234 Production of nerve growth factor , Epithelial irritation Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1274 Production of α-smooth muscle actin Cellular Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              77 Production, Critical Metabolites (CGA 330050 and CGA 265307) Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1233 Production, Nerve growth factor Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                249 Production, Reactive oxygen species Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                302 Production, VEGF-A Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2185 Proliferation of vascular smooth muscle cells Cellular Sep 5, 2023 Sep 5, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    57 Proliferation, Cell proliferation in the absence of cytotoxicity Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1041 Proliferation, smooth muscle Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1067 Proliferation/Clonal Expansion, aberrant basal cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1042 Proliferation/Clonal Expansion, smooth muscle Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1961 Prolongation of Action Potential Duration Organ Dec 13, 2021 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1962 Prolongation of QT interval Organ Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1842 Prolonged TLR9 activation Molecular Mar 19, 2021 Mar 26, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      599 prolonged, Depolarization of neuronal membrane Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Axonal sodium channel modulation leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1061 prolonged, elevation of serun CCK Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1075 prolonged, estrus Individual 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.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      334 Promotion, Hepatocelluar carcinoma Individual Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Uncharacterized liver damage leading to hepatocellular carcinoma
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1044 Promotion, mesovarian leiomyomas Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1053 Promotion, ovarian adenomas Tissue 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2092 Promotion, Ovarian Cancer Organ Jan 12, 2023 Mar 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1054 Promotion, ovarian granular cell tumors Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1066 Promotion, SIX-1 postive basal-type progenitor cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      211 Propagation, Oxidative stress Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Oxidation of iron in hemoglobin leading to hematotoxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2135 Prostate cancer Individual May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2136 prostatic intraepithelial neoplasia Tissue May 11, 2023 May 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor activation leading to prostate cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1585 Proteasomal dysfunction Molecular Jan 30, 2019 Jan 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • α-diketone-induced bronchiolitis obliterans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1509 Protein Adduct Formation Molecular Mar 26, 2018 Mar 26, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2029 protein-coupled estrogen receptor 1 (GPER) activation Molecular Jul 18, 2022 Jul 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1709 Psoriatic skin disease Individual Dec 27, 2019 Nov 23, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2085 Pulmonary epithelial injury Cellular Jan 9, 2023 Jul 11, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1458 Pulmonary fibrosis Organ Jul 26, 2017 May 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1092 Pulmonary Fibrosis, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2010 Pulmonary inflammation Organ May 31, 2022 May 31, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Adverse outcome pathway of PM-induced respiratory toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1967 Pyroptosis Cellular Jan 18, 2022 Jan 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • SARS-CoV-2 infection leading to pyroptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1593 Radicals of target chemicals Molecular Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1484 Receptor mediated endocytosis Molecular Oct 25, 2017 Oct 25, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1329 Reduce expression, BDNF (Brain-derived neurotrophic factor) Molecular Apr 13, 2017 May 31, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1757 Reduce, Sperm count Individual Apr 6, 2020 Apr 6, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Alkylation of DNA leading to reduced sperm count
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2024 Reduced complex sphingolipids Cellular Jul 14, 2022 Jul 19, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ceramide synthase inhibition leading to neural tube defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2210 Reduced cortical thickness Tissue Feb 2, 2024 Feb 2, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            945 reduced dimerization, ARNT/HIF1-alpha Molecular Nov 29, 2016 Mar 23, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            966 Reduced Estradiol in Circulation, Reduced steroidogenic production of estradiol in granulosa cells leading to decreased estradiol in circulation Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1135 Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            381 Reduced levels of BDNF Molecular Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2223 Reduced number of oligodendrocytes Cellular Apr 12, 2024 Apr 12, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            948 reduced production, VEGF Cellular Nov 29, 2016 Mar 28, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • AhR activation leading to preeclampsia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1883 Reduced size of the ovarian follicle pool Organ May 24, 2021 Nov 11, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1677 Reduced tidal volume Organ Jul 3, 2019 Feb 16, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Lung surfactant function inhibition leading to decreased lung function
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            674 Reduced, Ability to attract spawning mates Individual 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1007 Reduced, Anterior swim bladder inflation Organ 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            580 Reduced, Antiseptic incorporated in food Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1335 Reduced, BDNF (Brain-derived neurotrophic factor) Molecular Apr 13, 2017 May 31, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Network of SSRIs (selective serotonin reuptake inhibitors)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mental stress to depression
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Mental stress to agitation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            565 Reduced, Brood care Population 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1424 Reduced, fatty acid beta oxidation Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            587 Reduced, feeding 1 Individual Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Sodium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1017 Reduced, Feeding 2 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              561 Reduced, Food storage Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1419 Reduced, FXR activity Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1415 Reduced, GABA-A receptor activation Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              689 Reduced, Gonadotropin releasing hormone, hypothalamus Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1008 Reduced, Hearing Organ Nov 29, 2016 Feb 18, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1423 Reduced, HSD17B4 activity Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              690 Reduced, Luteinizing hormone (LH), plasma Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              692 Reduced, Maturation inducing steroid receptor signalling, oocyte Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              691 Reduced, Maturation inducing steroid, plasma Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 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, Meiotic prophase I/metaphase I transition, oocyte Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1405 Reduced, mucosal defense Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Helicobacter pylori to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1212 Reduced, Neuronal synaptic inhibition Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                678 Reduced, Pheromone release Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1403 Reduced, platelet aggregation Tissue Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1004 Reduced, Posterior swim bladder inflation Organ 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1422 Reduced, PPARalpha Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1413 Reduced, presynaptic neuron 2 activity Cellular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • presynaptic neuron 2 repression to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                383 Reduced, Presynaptic release of glutamate Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                687 Reduced, Prostaglandin E2 concentration, hypothalamus Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                671 Reduced, Prostaglandin F2alpha concentration, plasma Individual 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                672 Reduced, Prostaglandin F2alpha synthesis, ovary Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                685 Reduced, Prostaglandins, ovary Organ Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1402 Reduced, PTGS1 function Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NSAID induced PTGS1 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1408 Reduced, PTGS2 function Cellular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NSAID induced PTGS2 inactivation to gastric ulcer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                675 Reduced, Reproductive Success Individual 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1420 Reduced, SHP activity Molecular Jun 2, 2017 Jun 2, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NFE2/Nrf2 repression to steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                673 Reduced, Spawning behavior Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                592 Reduced, survival Population 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1005 Reduced, Swimming performance Individual Nov 29, 2016 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                586 Reduced, swimming speed Individual Nov 29, 2016 Nov 29, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1631 Reduction fo Pigmentation pattern Individual May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1626 reduction in melanin lead to decrease of pigmentation Tissue May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1629 Reduction in melanin level Cellular May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  965 reduction in ovarian granulosa cells synthesis of estradiol, Reduced steroidogenic production of estradiol in granulosa cells Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  408 reduction in ovarian granulosa cells, Aromatase (Cyp19a1) Cellular Nov 29, 2016 May 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  29 Reduction in, Angiogenic sprouts Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1464 Reduction of collagen crosslinking Tissue Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1628 Reduction of L-Dopaquinone Cellular May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1625 Reduction of L-Dopaquinone leads to melanin reduction Cellular May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1630 Reduction of melanosome level Tissue May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of tyrosinase leads to decreased population in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1610 Reduction, 17-OH-pregnenolone conversion in DHEA Cellular 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1611 Reduction, 17-OH-progesterone conversion in androstenedione Cellular 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      3 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Cellular Nov 29, 2016 Sep 16, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1789 Reduction, 17beta-estradiol synthesis by the undifferentiated gonad Cellular Jun 15, 2020 Jul 13, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      28 Reduction, Angiogenesis Molecular Nov 29, 2016 Jul 20, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Disruption of VEGFR Signaling Leading to Developmental Defects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      49 Reduction, Ca and HCO3 transport to shell gland Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      447 Reduction, Cholesterol transport in mitochondria Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      78 Reduction, Cumulative fecundity and spawning Individual Nov 29, 2016 Mar 20, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Estrogen receptor agonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1618 Reduction, egg production and spawning Individual Apr 18, 2019 Apr 18, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        106 Reduction, Eggshell thickness Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        446 Reduction, fetal/adult testosterone Tissue Nov 29, 2016 May 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        129 Reduction, Gonadotropins, circulating concentrations Organ Nov 29, 2016 May 9, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        64 Reduction, Ionotropic GABA receptor chloride channel conductance Cellular Nov 29, 2016 Feb 6, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        669 Reduction, Neuronal synaptic inhibition Cellular Nov 29, 2016 May 16, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        981 Reduction, NFAT/AP-1 complex formation Cellular Nov 29, 2016 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        219 Reduction, Plasma 17beta-estradiol concentrations Organ Nov 29, 2016 Sep 26, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1693 Reduction, Plasma progesterone concentration Tissue Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        221 Reduction, Plasma vitellogenin concentrations Organ Nov 29, 2016 Sep 16, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1692 Reduction, Progesterone synthesis Cellular Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1694 Reduction, progesterone uptake, decresed maturation Cellular Oct 3, 2019 Oct 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Luteinizing hormone receptor antagonism leading to reproductive dysfunction
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        243 Reduction, Prostaglandin E2 concentration Tissue Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Cyclooxygenase inhibition leading reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        274 Reduction, Testosterone synthesis by ovarian theca cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        413 Reduction, Testosterone synthesis in Leydig cells Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARα activation leading to impaired fertility in adult male rodents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • PPARα activation in utero leading to impaired fertility in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2139 Reduction, the ratio of 17beta-estradiol/11-Keto Testosterone in plasma Organ May 16, 2023 May 16, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        309 Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Cellular Nov 29, 2016 Sep 16, 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        285 Reduction, Vitellogenin synthesis in liver Tissue Nov 29, 2016 May 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1040 relaxation, smooth muscle Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1426 Release of G Proteins Cellular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1219 Release of Substance P (SP), Substance P increase in circulation Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          87 Release, Cytokine Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Frustrated phagocytosis-induced lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2031 Releasing, Apoptosis-Inducing Factor (AIF) Molecular Jul 18, 2022 Jul 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          985 Relief, Relief of atopic dermatitis Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1358 Repress, GABA-A receptor Molecular Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            495 Repressed expression of steroidogenic enzymes Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1902 Repression of Gbx2 expression Molecular Jul 14, 2021 Oct 7, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1277 Reproductive failure Individual Feb 15, 2017 Feb 15, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            445 Respiratory distress/arrest Organ Nov 29, 2016 Dec 20, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Acetylcholinesterase inhibition leading to acute mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Sodium channel inhibition leading to congenital malformations
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            397 Response, Keratinocytes Cellular Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1637 Retinaldehyde dehydrogenase inhibition Molecular May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Inhibition of retinaldehyde dehydrogenase leads to population decline
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1638 Retinoic acid (RA) synthesis decreased Cellular May 22, 2019 May 22, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1278 ROS formation Molecular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1592 ROS generation from photoactivated chemicals Molecular Feb 3, 2019 Jul 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Adverse outcome pathway on photochemical toxicity initiated by light exposure
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2186 Ryanodine receptor activation Molecular Sep 8, 2023 Sep 8, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Co-activation of IP3R and RyR leads to socio-economic burden through reduced IQ and non-cholinergic mechanisms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1738 SARS-CoV-2 cell entry Cellular Mar 1, 2020 Apr 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 infection leading to hyperinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 infection leading to pyroptosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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 of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1601 Scaling, Lichenification Organ Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  2006 Secondary genotoxicity Cellular May 25, 2022 May 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Interaction with lung resident cell membrane components leads to lung cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1437 Sensing of the stressor by pulmonary cells Molecular Jun 29, 2017 Jun 29, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    827 sensitisation, skin Organ Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Covalent Protein binding leading to Skin Sensitisation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1237 Sensitization, Immune system Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1583 Sensory axonal peripheral neuropathy Individual Jan 29, 2019 Jan 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Microtubule interacting drugs lead to peripheral neuropathy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1431 Serotonin 1A Receptor Agonism Molecular 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1390 Sexual behavior, decreased Individual May 3, 2017 May 17, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1904 six1b expression, increased Molecular Jul 14, 2021 Aug 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • GSK3beta inactivation leading to increased mortality via defects in developing inner ear
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      417 skewed, sex ratio Population Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • ER agonism leading to skewed sex ratios due to altered sexual differentiation in males
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1649 Snail, Zeb, Twist activation Molecular May 29, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1222 SP (Substance P) release, Local increase of SP Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1515 Spermatocyte depletion Tissue May 2, 2018 Jul 28, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1068 squamous metaplasia, aberrant basal cells Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        999 stabilization, co-repressor Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1000 stabilization, PPAR alpha co-repressor Molecular Nov 29, 2016 Apr 30, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Antagonist binding to PPARα leading to body-weight loss
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1788 Status epilepticus Individual May 21, 2020 May 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Acetylcholinesterase Inhibition Leading to Neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          650 Stimulation of adult Leydig cells via the Adrenal Corticosterone, Increased Glucocorticoid Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1706 Stimulation, TLR7/8 Molecular Dec 27, 2019 Nov 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2226 Stressor binding PPAR isoforms Molecular May 8, 2024 May 22, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1671 Substance - lung surfactant interaction Molecular Jul 3, 2019 Jul 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1495 Substance interaction with the lung resident cell membrane components Molecular Jan 2, 2018 May 17, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2118 Succinate dehydrogenase, inhibited Molecular Apr 3, 2023 May 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1964 Sudden cardiac death Individual Dec 13, 2021 Dec 13, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            2120 Superoxide generation, increased Cellular Apr 3, 2023 Apr 17, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1565 Suppressed AP-1 Cellular Dec 24, 2018 Dec 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1567 Suppressed DC activation Organ Dec 24, 2018 Dec 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1573 Suppressed MyD88 Cellular Jan 6, 2019 Mar 17, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1566 Suppressed NF-kB Cellular Dec 24, 2018 Dec 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1701 Suppression of NF-kB Molecular Nov 17, 2019 Nov 17, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1702 Suppression of T cell activation Cellular Nov 17, 2019 Mar 6, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1718 Suppression of IL-4 production Cellular Jan 5, 2020 Feb 24, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1717 Suppression of STAT5 binding to cytokine gene promoters Cellular Jan 5, 2020 Feb 24, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      456 Suppression, Constitutive androstane receptor, NR1l3 Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1046 Suppression, Estrogen receptor (ER) activity Molecular Nov 29, 2016 Feb 28, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      461 Suppression, HNF4alpha Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • HNF4alpha suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1202 Suppression, IL-2 and IL-4 production Cellular Nov 29, 2016 Jun 27, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      403 Suppression, Immune system Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      152 Suppression, Inflammatory cytokines Individual Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      982 Suppression, Suppression in mixed lymphocyte reaction (MLR) Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1203 Suppression, Suppression of production of cytotoxic T-cells Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1204 Suppression, Suppression of T-cell dependent antibody production Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            983 Suppression, Suppression of T-cell dependent antibody response (TDAR) Cellular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              450 Suppression, VLDL secretion Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1870 Sustentacular cells, decrease Cellular Apr 25, 2021 Mar 30, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1944 Synaptic dysfunction Organ Oct 26, 2021 Jan 4, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Various neuronal effects induced by elavl3, sox10, and mbp
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              89 Synthesis, De Novo Fatty Acid (FA) Cellular Nov 29, 2016 Mar 29, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Liver X Receptor (LXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1439 Systemic acute phase response Organ Jun 29, 2017 Dec 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              486 systemic inflammation leading to hepatic steatosis Organ Nov 29, 2016 Feb 24, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AKT2 activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1844 systemic inflammatory response syndrome Individual Mar 19, 2021 Mar 19, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1589 Systemic or topical administration of chemicals Molecular Feb 3, 2019 Feb 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1506 Testicular atrophy Organ Jan 21, 2018 Jul 1, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Histone deacetylase inhibition leading to testicular atrophy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1839 Testicular Cancer Organ Feb 12, 2021 Feb 12, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Androgen receptor antagonism leading to testicular cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1704 testJF Molecular Dec 5, 2019 Dec 5, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1708 Th17 cell migration and inflammation induction Cellular Dec 27, 2019 Nov 23, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  974 The binding of FK506 with FKBP12, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    975 The binding of FK506 with FKBP12, The binding of FK506 with FKBP12 Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1462 Thiol group of chemicals interact with sulfuhydryl groups of proteins to form thiol adducts Molecular Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1916 Thromboinflammation, Increased Organ Aug 4, 2021 Aug 4, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Endothelial cell dysfunction leading to thromboinflammation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1846 Thrombosis and Disseminated Intravascular Coagulation Individual Mar 25, 2021 Nov 25, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      277 Thyroid hormone synthesis, Decreased Cellular Nov 29, 2016 Nov 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Kidney dysfunction by decreased thyroid hormone
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      279 Thyroperoxidase, Inhibition Molecular Nov 29, 2016 Nov 4, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroperoxidase inhibition leading to altered amphibian metamorphosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of thyroid peroxidase leading to impaired fertility in fish
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      280 Thyroxine (T4) in neuronal tissue, Decreased Organ Nov 29, 2016 Apr 4, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1492 Tissue resident cell activation Cellular Nov 28, 2017 Mar 22, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased DNA damage leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Deposition of Energy Leading to Learning and Memory Impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1848 Toll Like Receptor (TLR) Dysregulation Molecular Mar 26, 2021 Nov 23, 2021
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Dysregulated underperforming Toll Like Receptors (TLRs) leading to high pathogen load
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1792 Toll-like receptor 4 activation Molecular Jul 9, 2020 Jul 9, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1963 Torsades de Pointes Organ Dec 13, 2021 Jan 29, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • hERG channel blockade leading to sudden cardiac death
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1438 Transcription of genes encoding acute phase proteins, Increased Organ Jun 29, 2017 Dec 18, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Substance interaction with lung resident cell membrane components leading to atherosclerosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1970 transposition of the great arteries Organ Feb 8, 2022 Feb 15, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1354 Treat, carbamazepine Molecular Apr 14, 2017 Apr 14, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Molecular events lead to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • presynaptic neuron 1 activation to epilepsy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1651 Treatment-resistant gastric cancer Tissue May 29, 2019 Oct 13, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1223 Trigeminal and/or vagal nerve excitation causes Airway Hyper-responsiveness,Cough, Dyspnea Tissue Nov 29, 2016 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1220 Trigeminal nerve activation Tissue Nov 29, 2016 Sep 24, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1229 TRPA1 activation, Chemical covalent binding to sulfhydyl group on TRPA1 receptor protein/ HEK293 fibroblast cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1227 TRPA1 activation, Chemical covalent binding to sulfhydyl group on TRPA1 receptor protein/NEK293 fibroblast cells Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1228 TRPA1 activation, Classic receptor binding / HEK 293 cells (fibroclast), cho cells (ovary), noncovalently linkked) Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1215 TRPA1 activation, TRPA1 Receptor Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1230 TRPV1 activation, TRPV1 Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1720 Trypsin inhibition Molecular Jan 8, 2020 Jan 8, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Trypsin inhibition leading to pancreatic acinar cell tumors
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              378 Tumorigenesis, Hepatocellular carcinoma Individual Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1624 Tyrosinase inhibition leads to L-Dopaquinone reduction Molecular May 3, 2019 May 3, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1150 Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Impaired function of osteocalcin and MGP Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1138 Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1120 Under carboxylated clotting factors will not assemble on cell surfaces , Failure to form clot Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1122 Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis Tissue Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1137 Under carboxylation of osteocalcin, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1168 Undercarboxylation of osteocalcin , Affects bone formation (osteoblast-osteoclast interaction, bone resorption) and glucose and lipid hoemostasis Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1512 Unfolded Protein Response Molecular Apr 4, 2018 Sep 14, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • CYP2E1 activation and formation of protein adducts leading to neurodegeneration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Inhibition of N-linked glycosylation leads to liver injury
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        • Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        1113 Unknown, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1114 Unknown, MIE Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • unknown MIE leading to renal failure and mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          • Unknown MIE altering cholesterol metabolism leading to decreased cognition
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1129 Unresolved blood loss (hemorrhage), Failure in vascular repair mechanisms Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1126 Unresolved blood loss, Failure in vascular repair mechanisms Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1128 Unresolved hemorrhage, Failure in vascular repair mechanisms Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                470 Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                54 Up Regulation, CD36 Molecular Nov 29, 2016 Mar 26, 2024
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • LXR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Pregnane X Receptor (PXR) activation leads to liver steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                80 Up Regulation, CYP1A1 Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • AhR activation leading to liver fibrosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                84 Up Regulation, CYP1B1 Molecular Nov 29, 2016 Dec 3, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  463 Up Regulation, FAS Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  466 Up Regulation, LDLR (low density lipoprotein receptor) Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  462 Up Regulation, SCD-1 Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NR1I3 (CAR) suppression leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • AhR activation leading to hepatic steatosis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1284 Up Regulation, SREBF2 Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  • G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  276 Up Regulation, TGFbeta1 expression Cellular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1285 Up Regulation, Unsaturated fatty acid Cellular Feb 15, 2017 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    695 Upregulated, Spindle assembly checkpoint protein Mad2-oocyte Molecular Nov 29, 2016 Sep 16, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    369 Uroporphyria Individual Nov 29, 2016 May 7, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Aryl hydrocarbon receptor activation leading to uroporphyria
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1762 Urothelial cell injury/death Cellular Apr 21, 2020 Apr 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1763 Urothelial Tumor Organ Apr 21, 2020 Apr 21, 2020
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2154 Uterine adenocarcinoma (endometrioid adenocarcinoma Type I) Organ Jul 27, 2023 Jul 27, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2178 Vascular barrier disruption Tissue Aug 21, 2023 Aug 21, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    • The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    2000 Vascular calcification Organ Apr 21, 2022 Apr 21, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2003 Vascular remodeling Organ Apr 22, 2022 Apr 22, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        2002 Ventricular remodeling Organ Apr 22, 2022 Apr 22, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          2032 Viable offspring, decreased Individual Jul 18, 2022 Jul 18, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1939 Viral infection and host-to-host transmission, proliferated Individual Oct 24, 2021 Dec 12, 2023
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            • Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            1165 Vitamin K inhibition, gamma-carboxylation of glutamate to Gla residues reduced in bone proteins e.g., periostin Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1111 weaj, Nov 29, 2016 Nov 29, 2016
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1465 Weak collagen matrix Tissue Aug 3, 2017 Aug 3, 2017
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                2062 Weak, Procuticle protection Organ Aug 28, 2022 Aug 28, 2022
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • Knickkopf leading to mortality
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1107 Weakened, Colony Population Nov 29, 2016 Jun 7, 2018
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                • 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
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                1645 Wnt ligand stimulation Molecular May 28, 2019 May 29, 2019
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  1648 β-catenin activation Molecular May 29, 2019 May 29, 2019