OECD View

AOPs displayed on this page have been developed in the context of projects that have been accepted for inclusion in the OECD Workplan. See the OECD website for more details.

Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits

Inhibition, NADH-ubiquinone oxidoreductase (complex I); Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I); Mitochondrial dysfunction; Impaired, Proteostasis; Neuroinflammation; Degeneration of dopaminergic neurons of the nigrostriatal pathway; Parkinsonian motor deficits;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.33 / iLibrary Page

Antagonist binding to PPARα leading to body-weight loss

Decreased, PPARalpha transactivation of gene expression; Decreased, Ketogenesis (production of ketone bodies); Not Increased, Circulating Ketone Bodies; Decreased, Body Weight; Increased, Catabolism of Muscle Protein; Binding of antagonist, PPAR alpha; stabilization, PPAR alpha co-repressor; Fatty Acid Beta Oxidation, Decreased;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 2.3

Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain

Reduction, Ionotropic GABA receptor chloride channel conductance; Occurrence, A paroxysmal depolarizing shift; Occurrence, Epileptic seizure; Binding at picrotoxin site, iGABAR chloride channel; Reduction, Neuronal synaptic inhibition; Generation, Amplified excitatory postsynaptic potential (EPSP);

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.15

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

Inhibition, NMDARs; N/A, Neurodegeneration; Decreased, Calcium influx; Binding of antagonist, NMDA receptors; Reduced levels of BDNF; Cell injury/death; Neuroinflammation; Impairment, Learning and memory;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.13

Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities

Binding of antagonist, NMDA receptors; Decreased, Calcium influx; Inhibition, NMDARs; Impairment, Learning and memory; Reduced levels of BDNF; Aberrant, Dendritic morphology; Decrease of synaptogenesis; Decrease of neuronal network function; Reduced, Presynaptic release of glutamate; Cell injury/death;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.22

Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations

Increase, Heritable mutations in offspring; Alkylation, DNA; Increase, Mutations; Inadequate DNA repair;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.11

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, Thiol/seleno-proteins involved in protection against oxidative stress; Oxidative Stress ; Glutamate dyshomeostasis; Cell injury/death; Neuroinflammation; Decrease of neuronal network function; Impairment, Learning and memory; Tissue resident cell activation; Increased Pro-inflammatory mediators; Decreased protection against oxidative stress;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.13

Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2

Activation, AhR; dimerization, AHR/ARNT; Altered, Cardiovascular development/function; Increase, COX-2 expression; Increase, Early Life Stage Mortality;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.27

Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)

Decrease, Population growth rate; Agonism, Androgen receptor; Reduction, Testosterone synthesis by ovarian theca cells; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells; Reduction, Plasma 17beta-estradiol concentrations; Reduction, Vitellogenin synthesis in liver; Reduction, Cumulative fecundity and spawning; Reduction, Plasma vitellogenin concentrations; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development; Reduction, Gonadotropins, circulating concentrations;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.12

Aromatase inhibition leading to reproductive dysfunction

Decrease, Population growth rate; Inhibition, Aromatase; Reduction, Plasma 17beta-estradiol concentrations; Reduction, Vitellogenin synthesis in liver; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells; Reduction, Cumulative fecundity and spawning; Reduction, Plasma vitellogenin concentrations;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.12

Protein Alkylation leading to Liver Fibrosis

N/A, Liver fibrosis; Alkylation, Protein; Cell injury/death; Activation, Stellate cells; Accumulation, Collagen; Tissue resident cell activation; Increased Pro-inflammatory mediators;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.14

Covalent Protein binding leading to Skin Sensitisation

Covalent Binding, Protein; sensitisation, skin; Activation, Keratinocytes; Activation, Dendritic Cells; Activation/Proliferation, T-cells;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.1

Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals

Thyroperoxidase, Inhibition; Thyroid hormone synthesis, Decreased; Thyroxine (T4) in serum, Decreased; Thyroxine (T4) in neuronal tissue, Decreased ; Cognitive Function, Decreased ; Hippocampal gene expression, Altered ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.10

Disruption of VEGFR Signaling Leading to Developmental Defects

Inhibition, VegfR2; Reduction, Angiogenesis; Impairment, Endothelial network; Insufficiency, Vascular; Increased, Developmental Defects;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.6

Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.

Mitochondrial dysfunction; Impairment, Learning and memory; Cell injury/death; N/A, Neurodegeneration; Overactivation, NMDARs; Increased, Intracellular Calcium overload; Decreased, Neuronal network function in adult brain; Binding of agonist, Ionotropic glutamate receptors; Neuroinflammation;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.23

Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment

Decrease of Thyroidal iodide; Thyroxine (T4) in neuronal tissue, Decreased ; Reduced levels of BDNF; Decrease of synaptogenesis; Impairment, Learning and memory; Thyroxine (T4) in serum, Decreased; Decrease of GABAergic interneurons; Inhibition, Na+/I- symporter (NIS); Decrease of neuronal network function; Thyroid hormone synthesis, Decreased;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.28

Aryl hydrocarbon receptor activation leading to uroporphyria

Activation, AhR; Oxidation, Uroporphyrinogen; Inhibition, UROD; Accumulation, Highly carboxylated porphyrins; Uroporphyria; Induction, CYP1A2/CYP1A5;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.7

Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF

Activation, AhR; dimerization, AHR/ARNT; reduced dimerization, ARNT/HIF1-alpha; Impairment, Endothelial network; Altered, Cardiovascular development/function; Increase, Early Life Stage Mortality; reduced production, VEGF;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.7

Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response

Interference, nuclear localization of NFAT; Reduction, NFAT/AP-1 complex formation; Impairment, T-cell dependent antibody response; Suppression, IL-2 and IL-4 production; Inhibition, Calcineurin Activity;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.38

Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation

Inhibition, Deiodinase 2; Decreased, Triiodothyronine (T3); Reduced, Posterior swim bladder inflation; Reduced, Swimming performance; Decrease, Population growth rate; Increased Mortality;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.35

Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation

Inhibition, Deiodinase 2; Decrease, Population growth rate; Decreased, Triiodothyronine (T3); Reduced, Anterior swim bladder inflation; Reduced, Swimming performance; Increased Mortality;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.35

Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation

Inhibition, Deiodinase 1; Decrease, Population growth rate; Decreased, Triiodothyronine (T3); Reduced, Posterior swim bladder inflation; Reduced, Swimming performance; Increased Mortality;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.35

Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation

Inhibition, Deiodinase 1; Decrease, Population growth rate; Decreased, Triiodothyronine (T3); Reduced, Anterior swim bladder inflation; Reduced, Swimming performance; Increased Mortality;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.35

Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation

Thyroperoxidase, Inhibition; Decrease, Population growth rate; Thyroid hormone synthesis, Decreased; Thyroxine (T4) in serum, Decreased; Reduced, Anterior swim bladder inflation; Reduced, Swimming performance; Decreased, Triiodothyronine (T3); Increased Mortality;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.35

Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis

Substance interaction with the lung resident cell membrane components; Increased, secretion of proinflammatory mediators; Increased, recruitment of inflammatory cells; Loss of alveolar capillary membrane integrity; Increased, activation of T (T) helper (h) type 2 cells; Increased, fibroblast proliferation and myofibroblast differentiation; Pulmonary fibrosis; Accumulation, Collagen;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.32

Inhibitor binding to topoisomerase II leading to infant leukaemia

Binding to (interferes with) topoisomerase II enzyme; MLL chromosomal translocation; Infant leukaemia; Increase, DNA double-strand breaks;

Created on: December 16, 2016 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.53 / iLibrary Page

Histone deacetylase inhibition leading to testicular atrophy

Histone deacetylase inhibition; Histone acetylation, increase; Cell cycle, disrupted; Apoptosis; Testicular atrophy; Spermatocyte depletion;

Created on: March 10, 2017 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.52 / iLibrary Page

Cyp2E1 Activation Leading to Liver Cancer

Activation of Cyp2E1; Oxidative Stress ; Hepatocytotoxicity; Induction, persistent proliferation/sustained proliferation; Liver Cancer;

Created on: May 30, 2017 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.24

Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation

Decrease, Coupling of oxidative phosphorylation; Decrease, Growth; Decrease, Adenosine triphosphate pool; Decrease, Cell proliferation;

Created on: May 24, 2018 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.92

Deposition of energy leading to lung cancer

Deposition of Energy; Increase, DNA strand breaks; Inadequate DNA repair; Increase, Mutations; Increase, Chromosomal aberrations; Increase, Cell Proliferation; Increase, lung cancer;

Created on: December 18, 2018 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.56

Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response

Impaired IL-1R1 signaling in T cell; Suppression of T cell activation; Inhibition, Nuclear factor kappa B (NF-kB); Impairment, T-cell dependent antibody response;

Created on: December 20, 2018 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.48

Oxidative DNA damage leading to chromosomal aberrations and mutations

Increase, Oxidative damage to DNA; Inadequate DNA repair; Increase, DNA strand breaks; Increase, Mutations; Increase, Chromosomal aberrations;

Created on: May 19, 2019 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.76

Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation

Inhibition, Aromatase; Reduction, 17beta-estradiol synthesis by the undifferentiated gonad ; Increased, Differentiation to Testis ; Increased, Male Biased Sex Ratio; Decrease, Population growth rate;

Created on: June 15, 2020 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.12

Chitin synthase 1 inhibition leading to mortality

Inhibition, Chitin synthase 1; Decrease, Cuticular chitin content; Increase, Premature molting; Increase, Mortality;

Created on: October 22, 2020 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.94

Androgen receptor agonism leading to male-biased sex ratio

Agonism, Androgen receptor; Increased, Differentiation to Testis ; Increased, Male Biased Sex Ratio; Decrease, Population growth rate;

Created on: March 10, 2021 / Last updated: May 26, 2024 / Status: WPHA/WNT Endorsed / Project number: 1.12

Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female

Reduction, Plasma 17beta-estradiol concentrations; Reduction, 17beta-estradiol synthesis by ovarian granulosa cells; impaired, Fertility; irregularities, ovarian cycle; reduction in ovarian granulosa cells, Aromatase (Cyp19a1);

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.21

PPARα activation in utero leading to impaired fertility in males

Activation, PPARα; impaired, Fertility; Decrease, Steroidogenic acute regulatory protein (STAR); Reduction, Cholesterol transport in mitochondria; Reduction, Testosterone synthesis in Leydig cells; Decrease, Translocator protein (TSPO); Malformation, Male reproductive tract; Decrease, testosterone levels ;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.21

Estrogen receptor antagonism leading to reproductive dysfunction

Decrease, Population growth rate; Antagonism, Estrogen receptor; Reduction, Vitellogenin synthesis in liver; Reduction, Plasma vitellogenin concentrations; Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development; Reduction, Cumulative fecundity and spawning;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.12

Sustained AhR Activation leading to Rodent Liver Tumours

N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects; Activation, Long term AHR receptor driven direct and indirect gene expression changes; Changes/Inhibition, Cellular Homeostasis and Apoptosis; Alterations, Cellular proliferation / hyperplasia; Formation, Hepatocellular and Bile duct tumors;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.7

AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)

Formation, Pro-mutagenic DNA Adducts; Tumorigenesis, Hepatocellular carcinoma; Increased, Induced Mutations in Critical Genes; Metabolism of AFB1, Production of Reactive Electrophiles; Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF); Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.8

Chemical binding to tubulin in oocytes leading to aneuploid offspring

Binding, Tubulin; Disruption, Microtubule dynamics; Disorganization, Meiotic Spindle; Increase, Aneuploid offspring; Altered, Meiotic chromosome dynamics; Altered, Chromosome number;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.11

Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat

Activation, Constitutive androstane receptor; Increase, cell proliferation (hepatocytes); Increase, hepatocellular adenomas and carcinomas; Increase, Preneoplastic foci (hepatocytes); Altered gene expression specific to CAR activation, Hepatocytes;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.17

Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors

Decrease, Intracellular pH; Increase, Tissue Degeneration, Necrosis & Atrophy ; Increase, Cell Proliferation; Increase, Respiratory or Squamous Metaplasia; Increase, Cytotoxicity; Increase, Site of Contact Nasal Tumors; Increase, Mutations in Critical Genes;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 2.7

Endocytic lysosomal uptake leading to liver fibrosis

Mitochondrial dysfunction; Cell injury/death; Endocytotic lysosomal uptake; Disruption, Lysosome; Increased Pro-inflammatory mediators; Leukocyte recruitment/activation; Activation, Stellate cells; Accumulation, Collagen; N/A, Liver fibrosis;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.47

Adverse outcome pathway on photochemical toxicity initiated by light exposure

ROS generation from photoactivated chemicals; Oxidation of membrane lipids; Oxidation/denatuation of membrane proteins; Inflamatory events in light-exposed tissues;

Created on: February 3, 2019 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.49

Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer

Treatment-resistant gastric cancer; Chronic reactive oxygen species; Porcupine-induced Wnt secretion and Wnt signaling activation; beta-catenin activation; Increases in cellular reactive oxygen species; Epithelial Mesenchymal Transition;

Created on: May 28, 2019 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.58

Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure

Thyroperoxidase, Inhibition; Thyroid hormone synthesis, Decreased; Thyroxine (T4) in serum, Decreased; Decreased, Triiodothyronine (T3); Increased Mortality; Decrease, Population growth rate; Altered, retinal layer structure; Altered, Visual function;

Created on: December 9, 2020 / Last updated: May 26, 2024 / Status: Under Review / Project number: 1.35

Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals

Activation, Pregnane-X receptor, NR1l2; Loss, Cochlear function; Thyroxine (T4) in neuronal tissue, Decreased ; Thyroxine (T4) in serum, Decreased; Induction, Upregulation of glucuronyltransferase activity; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered; Hippocampal gene expression, Altered ; Increased, Clearance of thyroxine from serum;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.9

Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol

Activation, PXR/SXR;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 2.5

Acetylcholinesterase inhibition leading to acute mortality

Increased Mortality; Acetylcholinesterase (AchE) Inhibition; Acetylcholine accumulation in synapses; Respiratory distress/arrest; Increased Cholinergic Signaling; Dysregulation of heart rate and vascular tone; Decrease, Population growth rate;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.3

Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)

Inhibition, Bile Salt Export Pump (ABCB11); Activation of specific nuclear receptors, Transcriptional change; Bile accumulation, Pathological condition; Release, Cytokine; Increase, Inflammation; Production, Reactive oxygen species; Peptide Oxidation; Cholestasis, Pathology;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.19

Oxidation of iron in hemoglobin leading to hematotoxicity

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); Altered regulation, Alpha hemoglobin; Propagation, Oxidative stress; Damaging, Red blood cells; hemolysis; Formation, Formation of hemoglobin adducts; Down Regulation, Gulcose-6-phosphate dehydrogenase; Increase, RBC congestion in liver; Increase, Liver and splenic hemosiderosis; N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number; N/A, Cyanosis occurs;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.16

Narcosis leading to respiratory failure

Accumulation, Biological membranes; Disruption, Membrane integrity;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.2

PPARα activation leading to hepatocellular adenomas and carcinomas in rodents

Activation, PPARα; Increase, Phenotypic enzyme activity; Increase, cell proliferation (hepatocytes); Increase, Clonal Expansion of Altered Hepatic Foci; Increase, hepatocellular adenomas and carcinomas;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.17

Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response

Increase, Allergic Respiratory Hypersensitivity Response; Activation, Dendritic Cells; Activation/Proliferation, T-cells; Covalent Binding, Protein; Increased, secretion of proinflammatory mediators;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.20

PPARα activation leading to impaired fertility in adult male rodents

impaired, Fertility; Increase, Luteinizing hormone (LH) ; Hyperplasia, Leydig cell; Increase proliferation, Leydig cell ; Activation, PPARα; Reduction, Testosterone synthesis in Leydig cells; Reduction, Cholesterol transport in mitochondria; Decrease, testosterone levels ;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.21

Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)

Activation, Androgen receptor; Increase, cell proliferation (hepatocytes); Increase, Preneoplastic foci (hepatocytes); Increase, hepatocellular adenomas and carcinomas;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.26

Kidney dysfunction by decreased thyroid hormone

Thyroid hormone synthesis, Decreased; Occurrence, Kidney toxicity; Decreased, Glomerular filtration; Decreased, Renal plasma flow; Decreased, Sodium reabsorption; Increased, Serum creatinine; Occurrence, Cystic dilatation (renal tubule); Occurrence, Cytoplasmic vacuolization (podocyte); Occurrence, Cytoplasmic vacuolization (Renal tubule); Decreased, Renal ability to dilute urine; Thyroxine (T4) in serum, Decreased;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.40

Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity

Inhibition, Phospholipase A; Damage, Lipid bilayer; Disturbance, Lysosomal function; Occurrence, Cytoplasmic vacuolization (hepatocyte); Occurrence, Ballooning degeneration (hepatocyte); Occurrence, Cytoplasmic vacuolization (kupffer cell); Induction, Microvesicular fat; Formation, Mallory body; Formation, Liver fibrosis; Occurrence, Cytoplasmic vacuolization (Bile duct cell); Mitochondrial dysfunction;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.39

EGFR Activation Leading to Decreased Lung Function

Activation, EGFR; Increase, Mucin production; Decrease, Lung function; Increase, goblet cell number;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.51

Peptide Oxidation Leading to Hypertension

Peptide Oxidation; KE1 : S-Glutathionylation, eNOS; KE2 : Decrease, GTPCH-1; KE3 : Decrease, Tetrahydrobiopterin; KE4 : Uncoupling, eNOS; KE6 : Depletion, Nitric Oxide; KE7 : Impaired, Vasodilation; KE8 : Increase, Vascular Resistance; Hypertension; KE5 : Decrease, AKT/eNOS activity;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.50

AhR activation leading to preeclampsia

Activation, AhR; dimerization, AHR/ARNT; reduced dimerization, ARNT/HIF1-alpha; reduced production, VEGF; abnormal, placental labyrinth vasculature morphology; increase, placental insufficiency; increase, Preeclampsia;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.42

Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity

Binding, Transthyretin in serum; Displacement, Serum thyroxine (T4) from transthyretin; Increased, Free serum thyroxine (T4); Increased, Uptake of thyroxine into tissue; Increased, Clearance of thyroxine from serum; Thyroxine (T4) in serum, Decreased; Thyroxine (T4) in neuronal tissue, Decreased ; Hippocampal gene expression, Altered ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered; Cognitive Function, Decreased ;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.41

Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage

Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis ; Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage); Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) ; Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal; Hemostasis, Depletion from blood of fully functional carboxylated clotting factors; 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; Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction; Impaired recruitment , Population trajectory; Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP; Osteoporosis and vascular calcification, Bone deterioration; Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin;

Created on: November 29, 2016 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.31

Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis

Inactivation of PPARγ; Activation of TGF-β signaling; Collagen Deposition; Lung fibrosis; Increase, Inflammation; Epithelial Mesenchymal Transition;

Created on: February 15, 2017 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.54

Substance interaction with lung resident cell membrane components leading to atherosclerosis

Transcription of genes encoding acute phase proteins, Increased; Systemic acute phase response; Atherosclerosis; Substance interaction with the lung resident cell membrane components; Increased, secretion of proinflammatory mediators;

Created on: June 29, 2017 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.55

Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity

Inhibition of mitochondrial DNA polymerase gamma (Pol gamma); Depletion, mtDNA ; Increase, Cytotoxicity (renal tubular cell); Occurrence, Kidney toxicity; Mitochondrial dysfunction;

Created on: October 25, 2017 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.43

Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity

Binding of substrate, endocytic receptor; Disturbance, Lysosomal function; Disruption, Lysosome; Increase, Cytotoxicity (renal tubular cell); Occurrence, Kidney toxicity;

Created on: October 25, 2017 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.43

Renal protein alkylation leading to kidney toxicity

Alkylation, Protein; Decrease, Mitochondrial ATP production; Increase, Cytotoxicity (renal tubular cell); Occurrence, Kidney toxicity; Mitochondrial dysfunction;

Created on: October 25, 2017 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.43

L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility

Blockade, L-Type Calcium Channels ; Decrease, Calcium currents; Decrease, Calcium binding to Troponin C; Decrease, Cardiac contractility ; Decrease, Cardiac ejection fraction ; Heart failure ; Disruption, Intracellular calcium mobilization; Disruption, Sarcomere assembly;

Created on: May 10, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.45

L-type calcium channel blockade leading to the disruption of cardiac electrophysiology

Created on: May 10, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.45

Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death

Decrease, Coupling of oxidative phosphorylation; Decrease, Adenosine triphosphate pool; Cell injury/death; Decrease, Growth;

Created on: May 24, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.92

Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium

Decrease, Coupling of oxidative phosphorylation; Increase, Cytosolic calcium; Cell injury/death; Decrease, Growth;

Created on: May 24, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.92

Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity

Decrease, Coupling of oxidative phosphorylation; Decrease, Adenosine triphosphate pool; Decreased Na/K ATPase activity; Increase, Cell membrane depolarization; Cell injury/death; Decrease, Growth;

Created on: May 24, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.92

Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion

Decrease, Coupling of oxidative phosphorylation; Increase, Glycolysis; Decrease, Glucose pool; Decrease, Cell proliferation; Decrease, Growth;

Created on: June 12, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.92

Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling

Decrease, Coupling of oxidative phosphorylation; Increase, Mitochondrial swelling; Cell injury/death; Decrease, Growth;

Created on: June 12, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.92

Inhibition of thyroid peroxidase leading to impaired fertility in fish

Thyroperoxidase, Inhibition; Thyroid hormone synthesis, Decreased; Reduction, Plasma 17beta-estradiol concentrations; Reduction, Plasma vitellogenin concentrations; Reduction, Cumulative fecundity and spawning;

Created on: September 18, 2018 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.59

L-type calcium channel blockade leading to hypotension

Created on: February 11, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.45

Inhibition of 5α-reductase leading to impaired fecundity in female fish

Inhibition, 5α-reductase; Decrease, dihydrotestosterone (DHT) level; Reduction, Plasma 17beta-estradiol concentrations; Reduction, Plasma vitellogenin concentrations; Reduction, Cumulative fecundity and spawning; Decrease, Population growth rate;

Created on: April 18, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.81

Inhibition of tyrosinase leads to decreased population in fish

Inhibition of tyrosinase ; Reduction of L-Dopaquinone; Reduction in melanin level; Reduction of melanosome level; Reduction fo Pigmentation pattern ; Decrease, Population growth rate;

Created on: May 3, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.78

Increased DNA damage leading to increased risk of breast cancer

Increase, DNA damage; N/A, Breast Cancer; Tissue resident cell activation; Increased Pro-inflammatory mediators; Increase in reactive oxygen and nitrogen species (RONS); Leukocyte recruitment/activation; Increase, Cell Proliferation (Epithelial Cells); Increased, Ductal Hyperplasia ; Increase, Mutations;

Created on: May 3, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.80

Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer

Increase in reactive oxygen and nitrogen species (RONS); Increase, DNA damage; Increase, Mutations; N/A, Breast Cancer; Increase, Cell Proliferation (Epithelial Cells); Tissue resident cell activation; Increased Pro-inflammatory mediators; Leukocyte recruitment/activation; Increased, Ductal Hyperplasia ;

Created on: May 7, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.80

Early-life stromal estrogen receptor activation by endocrine disrupting chemicals in the mammary gland leading to enhanced cancer risk

Created on: May 9, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.79

Inhibition of retinaldehyde dehydrogenase leads to population decline

Retinaldehyde dehydrogenase inhibition; Altered, Photoreceptor patterning; Decreased retinoic acid (RA) synthesis; Decreased plasma RA level; Altered, Visual function; Decrease, Population growth rate;

Created on: May 22, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.77

Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals

Antagonism, Thyroid Receptor ; Hippocampal gene expression, Altered ; Hippocampal anatomy, Altered ; Hippocampal Physiology, Altered; Cognitive Function, Decreased ;

Created on: June 8, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.84

Lung surfactant function inhibition leading to decreased lung function

Reduced tidal volume ; Loss of alveolar capillary membrane integrity; Inhibition of lung surfactant function; Alveolar collapse; Decrease, Lung function;

Created on: June 19, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.87

Frustrated phagocytosis-induced lung cancer

Frustrated phagocytosis; Release, Cytokine; Increased, recruitment of inflammatory cells; Increased, Reactive oxygen species; Increased, DNA damage and mutation; Increase, Cell Proliferation; Lung cancer;

Created on: July 3, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.86

5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring

Inhibition, 5α-reductase; Decrease, dihydrotestosterone (DHT) level; Decrease, androgen receptor activation; anogenital distance (AGD), decreased; Altered, Transcription of genes by the androgen receptor;

Created on: August 30, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.90

Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring

Antagonism, Androgen receptor; Decrease, androgen receptor activation; decrease, transcription of genes by AR ; anogenital distance (AGD), decreased;

Created on: August 30, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.90

Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring

Reduction, Testosterone synthesis in Leydig cells; Decrease, testosterone levels ; Decrease, dihydrotestosterone (DHT) level; Decrease, androgen receptor activation; Altered, Transcription of genes by the androgen receptor; anogenital distance (AGD), decreased;

Created on: August 30, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.90

Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease

Stimulation, TLR7/8; Increase, IL-23 from matured dendritic cells; Th17 cell migration and inflammation induction; Psoriatic skin disease; Maturation of TNF/iNOS-Producing Dendritic Cells;

Created on: December 27, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.75

Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)

Binding to estrogen receptor (ER)-α in immune cells; Induction of GATA3 expression; Increase of Th2 cells producing IL-4; Increase of anti-DNA antibody from autoreactive B cell; Exacerbation of systemic lupus erythematosus (SLE);

Created on: December 29, 2019 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.73

Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response

Inhibition of JAK3; Blockade of STAT5 phosphorylation; Suppression of STAT5 binding to cytokine gene promoters; Suppression of IL-4 production; Impairment of T-cell dependent antibody response;

Created on: January 5, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.74

Trypsin inhibition leading to pancreatic acinar cell tumors

Trypsin inhibition; Increased intestinal monitor peptide level; Increased blood CCK level; Increased exocrine secretion from pancreatic acinar cells; Acinar cell proliferation; Pancreatic acinar cell tumors;

Created on: January 8, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.60

Binding to ACE2 leading to lung fibrosis

Increased Angiotensin II ; Induced dysregulation of ACE2 ; Accumulation, Collagen; Lung fibrosis; Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R); Increased, Reactive oxygen species; Increased activation, Nuclear factor kappa B (NF-kB); Increased, secretion of proinflammatory mediators; Dysregulation, ACE2 expression and activity;

Created on: March 1, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality

Increased, secretion of proinflammatory mediators; SARS-CoV-2 cell entry ; Binding to ACE2; Increase, the risk of acute respiratory failure; Increased inflammatory immune responses; Increased Mortality; Toll Like Receptor (TLR) Dysregulation; Increased SARS-CoV-2 production; Interferon-I antiviral response, antagonized by SARS-CoV-2;

Created on: March 1, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring

Decrease, androgen receptor activation; Altered, Transcription of genes by the androgen receptor; Antagonism, Androgen receptor; Nipple retention (NR), increased;

Created on: May 11, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.108

Androgen receptor (AR) antagonism leading to decreased fertility in females

Antagonism, Androgen receptor; Altered, Transcription of genes by the androgen receptor; Granulosa cell proliferation of gonadotropin-independent follicles, Reduced; irregularities, ovarian cycle; impaired, Fertility; Decrease, androgen receptor activation;

Created on: May 19, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.109

Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory

Inhibition of 11β-HSD ; Decreased, plasma 11-ketotestosterone level; Impaired, Spermatogenesis; Decrease, Population growth rate; impaired, Fertility;

Created on: July 3, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.93

Inhibition of 11β-hydroxylase leading to decresed population trajectory

11β-hydroxylase inhibition; Decreased, plasma 11-ketotestosterone level; Decreased spermatogenesis ; Cortisol and 11β-(OH) testosterone decreased; Decreased plasma Cortisol level; decreased oocyte maturation; Decrease, Population growth rate; impaired, Fertility;

Created on: July 12, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.93

Chitinase inhibition leading to mortality

Inhibition, Chitinase ; Decrease, Digestion of old cuticle; Increase, Premature molting; Increase, Mortality;

Created on: October 21, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.94

Chitobiase inhibition leading to mortality

Inhibition, Chitobiase; Decrease, Digestion of old cuticle; Increase, Premature molting; Increase, Mortality;

Created on: October 21, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.94

Sulfonylureareceptor binding leading to mortality

Increase, Sulfonylurea receptor binding; Increase, Cell membrane depolarization; Increase, Opening of voltage-dependent calcium channel; Decrease, Cuticular chitin content; Increase, Premature molting; Increase, Mortality;

Created on: October 22, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.94

Thyroperoxidase inhibition leading to altered visual function via decreased eye size

Thyroperoxidase, Inhibition; Thyroid hormone synthesis, Decreased; Thyroxine (T4) in serum, Decreased; Decreased, Triiodothyronine (T3); Decreased, Eye size; Increased Mortality; Decrease, Population growth rate; Altered, Visual function;

Created on: December 9, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.35

Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning

Thyroperoxidase, Inhibition; Thyroid hormone synthesis, Decreased; Thyroxine (T4) in serum, Decreased; Decreased, Triiodothyronine (T3); Altered, Photoreceptor patterning; Increased Mortality; Decrease, Population growth rate; Altered, Visual function;

Created on: December 9, 2020 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.35

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 to ACE2; Neuroinflammation; N/A, Neurodegeneration; Encephalitis;

Created on: February 23, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation

Coagulation; Thrombosis and Disseminated Intravascular Coagulation; Increased SARS-CoV-2 production; SARS-CoV-2 cell entry ; Diminished protective oxidative stress response; Binding to ACE2; Interferon-I antiviral response, antagonized by SARS-CoV-2;

Created on: March 25, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia

Impaired gustatory nerve; Binding to ACE2; dysgeusia; Downregulation, ACE2; Increased Angiotensin II ; Imbalanced salty and sweet taste responses;

Created on: March 28, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis

Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R); Increased, secretion of proinflammatory mediators; Accumulation, Collagen; Lung fibrosis; Increased activation, Nuclear factor kappa B (NF-kB); Increased, Reactive oxygen species;

Created on: March 30, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis

Induced dysregulation of ACE2 ; N/A, Liver fibrosis; Increased Ang II type 1 receptor (AT1R); Increased, extracellular matrix deposition; Increased, Reactive oxygen species; Increase plasma Ang II;

Created on: March 30, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation

Fibrinolysis, decreased; Bradykinin system, hyperactivated; Increased, secretion of proinflammatory mediators; Increased, recruitment of inflammatory cells; Hyperinflammation;

Created on: April 20, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)

Binding to ACE2; SARS-CoV-2 cell entry ; Sustentacular cells, decrease ; olfactory sensory neurons, decrease ; Olfactory epithelium degeneration; impaired olfactory function (anosmia) ; Increased SARS-CoV-2 production;

Created on: April 25, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)

Binding to ACE2; SARS-CoV-2 cell entry ; blood brain barrier disruption ; Thrombosis and Disseminated Intravascular Coagulation; Cerebrovascular disease (stroke);

Created on: April 27, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Bulky DNA adducts leading to mutations

Bulky DNA adducts, increase; Inadequate DNA repair; Increase, Mutations;

Created on: May 17, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.11

Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary

Inhibition of ALDH1A (RALDH); Decreased, all-trans retinoic acid (atRA) concentration; Disrupted meiotic initiation of fetal oogonia of the ovary; Reduced size of the ovarian follicle pool ; impaired, Fertility; irregularities, ovarian cycle;

Created on: May 24, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.97

Endothelial cell dysfunction leading to thromboinflammation

Endothelial cell dysfunction ; Platelet-neutrophil interactions, Increased ; Release, Cytokine; Platelet activation, Increased; Neutrophil activation, Increased ; Thromboinflammation, Increased ;

Created on: August 4, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption

Binding to ACE2; SARS-CoV-2 cell entry ; Increased SARS-CoV-2 production; Intestinal barrier, disruption; Interferon-I antiviral response, antagonized by SARS-CoV-2;

Created on: September 13, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis

Binding to ACE2; Dysregulation, ACE2 expression and activity; Gut microbiota, alteration;

Created on: October 19, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation

Binding to ACE2; SARS-CoV-2 cell entry ; Interferon-I antiviral response, antagonized by SARS-CoV-2; Increased SARS-CoV-2 production; Viral infection and host-to-host transmission, proliferated;

Created on: October 24, 2021 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.96

Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity

Inhibition, Mitochondrial Electron Transport Chain Complexes; Increase, Cytotoxicity (renal tubular cell); Increase, Oxidative Stress; Occurrence, Kidney toxicity; Mitochondrial dysfunction;

Created on: January 31, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.99

Activation of the AhR leading to metastatic breast cancer

Activation, AhR; Increase, Inflammation; Apoptosis; Increased, Motility; Increased, Migration (Endothelial Cells); Increased, Invasion; Increase, angiogenesis; Increased, tumor growth; metastatic breast cancer;

Created on: February 15, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.105

Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia

Suppression, Estrogen receptor (ER) activity; Increased, secretion of GnRH from hypothalamus; Increased, secretion of LH from anterior pituitary; Increased, Steroidogenic acute regulatory protein (StAR) ; Increased, estrogens ; Increased, circulating estrogen levels; Hyperplasia, ovarian epithelium; Promotion, ovarian adenomas; Promotion, Ovarian Cancer ;

Created on: February 25, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.104

Binding to voltage gate sodium channels during development leads to cognitive impairment

Binding to voltage-gated sodium channel; Disruption of sodium channel gating kinetics; Disruption, action potential; Altered neurotransmission in development; Hippocampal anatomy, Altered ; Altered function of the brain; Impairment, Learning and memory;

Created on: March 15, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.91

DNA damage and mutations leading to Metastatic Breast Cancer

Increased, DNA damage and mutation; Inadequate DNA repair; Increase, Mutations; Increased microRNA expression; Decreased SIRT1 expression; Increased activation, Nuclear factor kappa B (NF-kB); Antagonism, Estrogen receptor; Epithelial Mesenchymal Transition; metastatic breast cancer; Increase Chromosomal Aberrations;

Created on: March 21, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.103

Antagonism of Smoothened receptor leading to orofacial clefting

Antagonism, Smoothened receptor; Decrease, GLI1/2 translocation to nucleus ; Decrease, GLI1/2 target gene expression; Decrease, Cell proliferation; Decrease, palatal shelf outgrowth; Orofacial clefting; Decrease, Sonic Hedgehog second messenger production; Decrease, Smoothend relocation and activation ; Apoptosis;

Created on: July 13, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.101

Succinate dehydrogenase inactivation leading to cancer

Created on: November 16, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.106

Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons

Binding of agonist, Ionotropic glutamate receptors; Overactivation, NMDARs; Loss of drebrin; Synaptic dysfunction; Impairment, Learning and memory; Increased, Intracellular Calcium overload; Decrease of neuronal network function;

Created on: December 11, 2022 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.107

Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress

Inhibition, Mitochondrial Electron Transport Chain Complexes; Mitochondrial dysfunction; Oxidative Stress ; Cell injury/death; Increase, Cardiac remodelling; Decrease, Cardiac contractility ; Decrease Left Ventricular function;

Created on: January 5, 2023 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.102

Mitochondrial complexes inhibition leading to heart failure via decreased ATP production

Inhibition, Mitochondrial Electron Transport Chain Complexes; Mitochondrial dysfunction; Decrease, Mitochondrial ATP production; Decrease, Cardiac contractility ; Decrease Left Ventricular function;

Created on: January 5, 2023 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.102

Decrease, GLI1/2 target gene expression leads to orofacial clefting

Decrease, GLI1/2 target gene expression; Decrease, Sonic Hedgehog second messenger production; Decrease, Cell proliferation; Decrease, palatal shelf outgrowth; Orofacial clefting; Apoptosis;

Created on: March 31, 2023 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.101

Decrease, cholesterol synthesis leads to orofacial clefting

Orofacial clefting; Decrease, palatal shelf outgrowth; Decrease, Cell proliferation; Decrease, Sonic Hedgehog second messenger production; Apoptosis; Decrease, GLI1/2 target gene expression; Decrease, GLI1/2 translocation to nucleus ;

Created on: June 28, 2023 / Last updated: May 26, 2024 / Status: Under Development / Project number: 1.101