AOPs With OECD Status

WPHA/WNT Endorsed

Open for citation & comment

Title Point of Contact MIE AO OECD Project
Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations Evgeniia Kazymova 97: Alkylation, DNA 336: Increase, Heritable mutations in offspring 1.11
Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Evgeniia Kazymova 25: Agonism, Androgen receptor 360: Decrease, Population trajectory 1.12
Antagonist binding to PPARα leading to body-weight loss Agnes Aggy 998: Binding of antagonist, PPAR alpha 864: Decreased, Body Weight 2.3
Aromatase inhibition leading to reproductive dysfunction Cataia Ives 36: Inhibition, Aromatase 360: Decrease, Population trajectory 1.12
Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 Allie Always 18: Activation, AhR 947: Increase, early life stage mortality 1.27
Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Arthur Author 18: Activation, AhR 947: Increase, Early Life Stage Mortality 1.7
Aryl hydrocarbon receptor activation leading to uroporphyria Allie Always 18: Activation, AhR 369: Uroporphyria 1.7
Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Allie Always 875: Binding of agonist, Ionotropic glutamate receptors 341: Impairment, Learning and memory 1.23
Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain Cataia Ives 667: Binding at picrotoxin site, iGABAR chloride channel 613: Occurrence, Epileptic seizure 1.15
Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Agnes Aggy 201: Binding of antagonist, NMDA receptors 341: Impairment, Learning and memory 1.22
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 Arthur Author 201: Binding of antagonist, NMDA receptors 352: N/A, Neurodegeneration and 341: Impairment, Learning and memory 1.13
Covalent Protein binding leading to Skin Sensitisation Agnes Aggy 396: Covalent Binding, Protein 827: sensitisation, skin 1.1
Cyp2E1 Activation Leading to Liver Cancer Agnes Aggy 1391: Activation of Cyp2E1 1395: Liver Cancer 1.24
Histone deacetylase inhibition leading to testicular atrophy Brendan Ferreri-Hanberry 1502: Histone deacetylase inhibition 1506: Testicular atrophy 1.52
Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Arthur Author 424: Inhibition, Na+/I- symporter (NIS) 341: Impairment, Learning and memory 1.28
Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Cataia Ives 888: Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) 896: Parkinsonian motor deficits 1.33
Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Evgeniia Kazymova 279: Thyroperoxidase, Inhibition 402: Cognitive Function, Decreased 1.10
Protein Alkylation leading to Liver Fibrosis Brendan Ferreri-Hanberry 244: Alkylation, Protein 344: N/A, Liver fibrosis 1.14

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Title Point of Contact MIE AO OECD Project
Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response Cataia Ives 980: Inhibition, Calcineurin Activity 984: Impairment, T-cell dependent antibody response 1.38

EAGMST Approved

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Title Point of Contact MIE AO OECD Project
Chitin synthase 1 inhibition leading to mortality Brendan Ferreri-Hanberry 1522: Inhibition, Chitin synthase 1 350: Increase, Mortality 1.94
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation Allie Always 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92

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Title Point of Contact MIE AO OECD Project
Inhibitor binding to topoisomerase II leading to infant leukaemia Agnes Aggy 1252: Binding to (interferes with) topoisomerase II enzyme 1254: Infant leukaemia 1.53

Under development: Not open for comment. Do not cite

Title Point of Contact MIE AO OECD Project
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 Brendan Ferreri-Hanberry 1487: Binding, Thiol/seleno-proteins involved in protection against oxidative stress 341: Impairment, Learning and memory 1.13
Deposition of energy leading to lung cancer Brendan Ferreri-Hanberry 1686: Direct Deposition of Energy 1556: Increase, lung cancer 1.56

Under Development: Contributions and Comments Welcome

Title Point of Contact MIE AO OECD Project
Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Allie Always 1009: Inhibition, Deiodinase 1 351: Increased Mortality and 360: Decrease, Population trajectory 1.35
Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Agnes Aggy 1009: Inhibition, Deiodinase 1 351: Increased Mortality and 360: Decrease, Population trajectory 1.35
Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Arthur Author 1002: Inhibition, Deiodinase 2 351: Increased Mortality and 360: Decrease, Population trajectory 1.35
Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Brendan Ferreri-Hanberry 1002: Inhibition, Deiodinase 2 351: Increased Mortality and 360: Decrease, Population trajectory 1.35
Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Evgeniia Kazymova 279: Thyroperoxidase, Inhibition 351: Increased Mortality and 360: Decrease, Population trajectory 1.35

EAGMST Under Review

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Title Point of Contact MIE AO OECD Project
AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC) Agnes Aggy 373: Formation, Pro-mutagenic DNA Adducts 378: Tumorigenesis, Hepatocellular carcinoma 1.8
Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Allie Always 408: reduction in ovarian granulosa cells, Aromatase (Cyp19a1) 406: impaired, Fertility and 405: irregularities, ovarian cycle 1.21
Chemical binding to tubulin in oocytes leading to aneuploid offspring Cataia Ives 718: Binding, Tubulin 728: Increase, Aneuploid offspring 1.11
Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat Brendan Ferreri-Hanberry 715: Activation, Constitutive androstane receptor 719: Increase, hepatocellular adenomas and carcinomas 1.17
Disruption of VEGFR Signaling Leading to Developmental Defects Cataia Ives 305: Inhibition, VegfR2 1001: Increased, Developmental Defects 1.6
Estrogen receptor antagonism leading to reproductive dysfunction Evgeniia Kazymova 112: Antagonism, Estrogen receptor 360: Decrease, Population trajectory 1.12
Impaired IL-1R1 signaling leading to increased susceptibility to infection Cataia Ives 1700: Impaired IL-1R1 signaling 986: Increase, Increased susceptibility to infection 1.48
Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors Cataia Ives 867: Decrease, Intracellular pH 872: Increase, Site of Contact Nasal Tumors 2.7
PPARα activation in utero leading to impaired fertility in males Arthur Author 227: Activation, PPARα 406: impaired, Fertility and 348: Malformation, Male reproductive tract 1.21
Sustained AhR Activation leading to Rodent Liver Tumours Allie Always 165: Activation, Long term AHR receptor driven direct and indirect gene expression changes 856: Formation, Hepatocellular and Bile duct tumors 1.7

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Title Point of Contact MIE AO OECD Project
Chronic reactive oxygen species leading to human treatment-resistant gastric cancer Agnes Aggy 1753: Chronic reactive oxygen species 1651: Treatment-resistant gastric cancer 1.58
Oxidative DNA damage leading to chromosomal aberrations and mutations Brendan Ferreri-Hanberry 1634: Increase, Oxidative damage to DNA 185: Increase, Mutations and 1636: Increase, Chromosomal aberrations 1.76

Under development: Not open for comment. Do not cite

Title Point of Contact MIE AO OECD Project
Adverse outcome pathway on photochemical toxicity initiated by light exposure Evgeniia Kazymova 1592: ROS generation from photoactivated chemicals 1599: Inflamatory events in light-exposed tissues 1.49
Endocytic lysosomal uptake leading to liver fibrosis Allie Always 1539: Endocytotic lysosomal uptake 344: N/A, Liver fibrosis 1.47
Substance interaction with the lung resident cell membrane components leading to lung fibrosis Cataia Ives 1495: Interaction with the lung resident cell membrane components 1458: Pulmonary fibrosis 1.32

Under Development

Open for citation & comment

Title Point of Contact MIE AO OECD Project
Inhibition of 5α-reductase leading to impaired fecundity in female fish Cataia Ives 1617: 5α-reductase, inhibition 360: Decrease, Population trajectory 1.81
Inhibition of tyrosinase leads to decreased population in fish Agnes Aggy 1627: Inhibition of tyrosinase 360: Decrease, Population trajectory 1.78
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cell death Evgeniia Kazymova 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92

Open for comment. Do not cite

Title Point of Contact MIE AO OECD Project
Binding of viral S-glycoprotein to ACE2 receptor leading to acute respiratory distress associated mortality Evgeniia Kazymova 1739: ACE2 binding to viral S-protein 351: Increased Mortality 1.96
Induced dysregulation of Angiotensin-converting enzyme 2 leading to lung fibrosis Allie Always 1740: ACE2 inhibition 1276: Lung fibrosis 1.96
Inhibition of thyroid peroxidase leading to impaired fertility in fish Cataia Ives 279: Thyroperoxidase, Inhibition 78: Reduction, Cumulative fecundity and spawning 1.59
Lung surfactant function inhibition leading to decreased lung function Brendan Ferreri-Hanberry 1672: Inhibition of lung surfactant function 1250: Decrease, Lung function 1.87

Open for adoption

Title Point of Contact MIE AO OECD Project
Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat) Evgeniia Kazymova 785: Activation, Androgen receptor 719: Increase, hepatocellular adenomas and carcinomas 1.26
Oxidation of iron in hemoglobin leading to hematotoxicity Cataia Ives 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) 321: N/A, Cyanosis occurs 1.16
Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Evgeniia Kazymova 239: Activation, Pregnane-X receptor, NR1l2 319: Loss, Cochlear function 1.9

Not under active development

Title Point of Contact MIE AO OECD Project
Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage Brendan Ferreri-Hanberry 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 and 1138: Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP and 1169: 1136: Impaired recruitment , Population trajectory 1.31
Peptide Oxidation Leading to Hypertension Brendan Ferreri-Hanberry 209: Peptide Oxidation 952: Hypertension 1.50
Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol Brendan Ferreri-Hanberry 245: Activation, PXR/SXR 2.5
PPARα activation leading to impaired fertility in adult male rodents Evgeniia Kazymova 227: Activation, PPARα 406: impaired, Fertility 1.21
Renal protein alkylation leading to kidney toxicity Evgeniia Kazymova 244: Alkylation, Protein 814: Occurrence, Kidney toxicity 1.43

Under development: Not open for comment. Do not cite

Title Point of Contact MIE AO OECD Project
5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring Allie Always 1617: 5α-reductase, inhibition 1688: decrease, male anogenital distance 1.90
AhR activation leading to preeclampsia Agnes Aggy 18: Activation, AhR 1893: increase, Preeclampsia 1.42
Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring Evgeniia Kazymova 26: Antagonism, Androgen receptor 1688: decrease, male anogenital distance 1.90
Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Allie Always 1851: Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) 1276: Lung fibrosis 1.96
Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis Cataia Ives 1739: ACE2 binding to viral S-protein 1.96
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 Agnes Aggy 1739: ACE2 binding to viral S-protein 1841: Encephalitis 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) Agnes Aggy 1739: ACE2 binding to viral S-protein 1875: Cerebrovascular disease (stroke) 1.96
Binding of SARS-CoV-2 to ACE2 in enterocytes leads to increased intestinal permeability Cataia Ives 1739: ACE2 binding to viral S-protein 1932: Gastrointestinal disorders 1.96
Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia Agnes Aggy 1739: ACE2 binding to viral S-protein 1850: dysgeusia 1.96
Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE) Cataia Ives 1710: Binding to estrogen receptor (ER)-α in immune cells 1714: Exacerbation of systemic lupus erythematosus (SLE) 1.73
Chitinase inhibition leading to mortality Evgeniia Kazymova 1806: Increase, Chitinase inhibition 350: Increase, Mortality 1.94
Chitobiase inhibition leading to mortality Cataia Ives 1807: Increase, Chitobiase inhibition 350: Increase, Mortality 1.94
Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) Arthur Author 41: Inhibition, Bile Salt Export Pump (ABCB11) 357: Cholestasis, Pathology 1.19
Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation Cataia Ives 1866: Fibrinolysis, decreased and 1867: Bradykinin system, hyperactivated 1868: Hyperinflammation 1.96
Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Cataia Ives 1688: decrease, male anogenital distance 1.90
Early-life stromal estrogen receptor activation by endocrine disrupting chemicals in the mammary gland leading to enhanced cancer risk Cataia Ives 1.79
EGFR Activation Leading to Decreased Lung Function Cataia Ives 941: Activation, EGFR 1250: Decrease, Lung function 1.51
Frustrated phagocytosis-induced lung cancer Arthur Author 1668: Frustrated phagoytosis 1670: Lung cancer 1.86
Increased DNA damage leading to increased risk of breast cancer Allie Always 1194: Increase, DNA damage 185: Increase, Mutations and 1192: Increased, Ductal Hyperplasia and 1193: N/A, Breast Cancer 1.80
Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Evgeniia Kazymova 1632: Increase in reactive oxygen and nitrogen species (RONS) 1194: Increase, DNA damage and 185: Increase, Mutations and 1192: Increased, Ductal Hyperplasia and 1193: N/A, Breast Cancer 1.80
Increased susceptibility to viral entry and coronavirus production leading to thrombosis and disseminated intravascular coagulation Arthur Author 1738: Increased susceptibility to viral entry 1847: Increased coronavirus production and 1846: Thrombosis and Disseminated Intravascular Coagulation 1.96
Inhibition of 11β-hydroxylase leading to decresed population trajectory Allie Always 1796: 11β-hydroxylase inhibition 360: Decrease, Population trajectory 1.93
Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory Agnes Aggy 1799: Inhibition of 11β-HSD 360: Decrease, Population trajectory 1.93
Inhibition of ALDH1A (RALDH) causing reduced all-trans retinoic acid levels leading to impaired fertility, females Cataia Ives 1880: Inhibition of ALDH1A2 (RALDH2) 972: Decreased fertility, Reduced number of oocytes ovulated 1.97
Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis Evgeniia Kazymova 1740: ACE2 inhibition 344: N/A, Liver fibrosis 1.96
Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response Brendan Ferreri-Hanberry 1715: Inhibition of JAK3 1719: Impairment of T-cell dependent antibody response 1.74
Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Agnes Aggy 1481: Inhibition of mitochondrial DNA polymerase gamma (Pol gamma) 814: Occurrence, Kidney toxicity 1.43
Kidney dysfunction by decreased thyroid hormone Arthur Author 277: Thyroid hormone synthesis, Decreased 814: Occurrence, Kidney toxicity 1.40
L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility Arthur Author 1529: Blockade, L-Type Calcium Channels 1535: Heart failure 1.45
L-type calcium channel blockade leading to hypotension Cataia Ives 1.45
L-type calcium channel blockade leading to the disruption of cardiac electrophysiology Agnes Aggy 1.45
Narcosis leading to respiratory failure Allie Always 46: Accumulation, Biological membranes 1.2
Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis Brendan Ferreri-Hanberry 1270: Inactivation of PPARγ 1276: Lung fibrosis 1.54
PPARα activation leading to hepatocellular adenomas and carcinomas in rodents Cataia Ives 227: Activation, PPARα 719: Increase, hepatocellular adenomas and carcinomas 1.17
Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity Allie Always 1486: Binding of substrate, endocytic receptor 814: Occurrence, Kidney toxicity 1.43
SARS-CoV-2 infection leading to thromboinflammation Arthur Author 1739: ACE2 binding to viral S-protein 1916: Thromboinflammation, Increased 1.96
SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia) Arthur Author 1739: ACE2 binding to viral S-protein 1873: impaired olfactory function (anosmia) 1.96
Sars-CoV-2 Interferon-I antiviral response antagonism and increased viral production leading to viral infection proliferation Arthur Author 1739: ACE2 binding to viral S-protein 1939: Viral infection and host-to-host transmission, proliferated 1.96
Secretion of inflammatory cytokines after cellular sensing of the stressor leading to plaque progression Arthur Author 1437: Sensing of the stressor by pulmonary cells 1443: Plaque progression in arteries 1.55
Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease Evgeniia Kazymova 1706: Stimulation, TLR7/8 1709: Psoriatic skin disease 1.75
Sulfonylureareceptor binding leading to mortality Arthur Author 1525: Increase, Sulfonylurea receptor binding 350: Increase, Mortality 1.94
Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Evgeniia Kazymova 1656: Antagonism, Thyroid Receptor 402: Cognitive Function, Decreased 1.84
Trypsin inhibition leading to pancreatic acinar cell tumors Arthur Author 1720: Trypsin inhibition 1725: Pancreatic acinar cell tumors 1.60
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased lipid storage Cataia Ives 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased lipid peroxidation Arthur Author 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased protein oxidation Agnes Aggy 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via oxidative DNA damage Brendan Ferreri-Hanberry 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92

Under Development: Contributions and Comments Welcome

Title Point of Contact MIE AO OECD Project
Acetylcholinesterase inhibition leading to acute mortality Cataia Ives 12: Acetylcholinesterase (AchE) Inhibition 351: Increased Mortality and 360: Decrease, Population trajectory 1.3
Covalent Binding of Low Molecular Weight Organic Chemicals to Proteins leads to Sensitisation (Sensitization) of the Respiratory Tract Arthur Author 396: Covalent Binding, Protein 313: Increase, Allergic Respiratory Hypersensitivity Response 1.20
Inhibition of retinaldehyde dehydrogenase leads to population decline Arthur Author 1637: Retinaldehyde dehydrogenase inhibition 360: Decrease, Population trajectory 1.77
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Allie Always 957: Binding, Transthyretin in serum 402: Cognitive Function, Decreased 1.41
Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity Agnes Aggy 828: Inhibition, Phospholipase A 840: Formation, Liver fibrosis 1.39