AOPs With OECD Status

WPHA/WNT Endorsed

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Title Point of Contact MIE AO OECD Project
Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations Carole Yauk 97: Alkylation, DNA 336: Increase, Heritable mutations in offspring 1.11
Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Dan Villeneuve 25: Agonism, Androgen receptor 360: Decrease, Population trajectory 1.12
Antagonist binding to PPARα leading to body-weight loss Kurt A. Gust 998: Binding of antagonist, PPAR alpha 864: Decreased, Body Weight 2.3
Aromatase inhibition leading to reproductive dysfunction Dan Villeneuve 36: Inhibition, Aromatase 360: Decrease, Population trajectory 1.12
Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 Markus Hecker 18: Activation, AhR 1.27
Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Amani Farhat 18: Activation, AhR 947: Increase, Early Life Stage Mortality 1.7
Aryl hydrocarbon receptor activation leading to uroporphyria Amani Farhat 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. Anna Price 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 Ping Gong 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 Anna Price 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 Florianne Tschudi-Monnet 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 Sharon Munn 396: Covalent Binding, Protein 827: sensitisation, skin 1.1
Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Anna Price 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 Andrea Terron 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 Kevin Crofton 279: Thyroperoxidase, Inhibition 402: Cognitive Function, Decreased 1.10
Protein Alkylation leading to Liver Fibrosis Brigitte Landesmann 244: Alkylation, Protein 344: N/A, Liver fibrosis 1.14

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) Ted Simon 373: Formation, Pro-mutagenic DNA Adducts 378: Tumorigenesis, Hepatocellular carcinoma 1.8
Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Elise Grignard 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 Francesco Marchetti 718: Binding, Tubulin 728: Increase, Aneuploid offspring 1.11
Chitin synthase 1 inhibition leading to mortality Simon Schmid 1522: Inhibition, Chitin synthase 1 350: Increase, Mortality 1.94
Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat Kristin Lichti-Kaiser 715: Activation, Constitutive androstane receptor 719: Increase, hepatocellular adenomas and carcinomas 1.17
Cyp2E1 Activation Leading to Liver Cancer Francina Webster 1391: Activation of Cyp2E1 1395: Liver Cancer 1.24
Disruption of VEGFR Signaling Leading to Developmental Defects Tom Knudsen 305: Inhibition, VegfR2 1001: Increased, Developmental Defects 1.6
Estrogen receptor antagonism leading to reproductive dysfunction Dan Villeneuve 112: Antagonism, Estrogen receptor 360: Decrease, Population trajectory 1.12
Histone deacetylase inhibition leading to testicular atrophy Shihori Tanabe 1502: Histone deacetylase inhibition 1506: Testicular atrophy 1.52
Impaired IL-1R1 signaling leading to increased susceptibility to infection Yutaka Kimura 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 Justin Teeguarden 867: Decrease, Intracellular pH 872: Increase, Site of Contact Nasal Tumors 2.7
PPARα activation in utero leading to impaired fertility in males Elise Grignard 227: Activation, PPARα 406: impaired, Fertility and 348: Malformation, Male reproductive tract 1.21
Sustained AhR Activation leading to Rodent Liver Tumours Rick Becker 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
Inhibitor binding to topoisomerase II leading to infant leukaemia Andrea Terron 1252: Binding to (interferes with) topoisomerase II enzyme 1254: Infant leukaemia 1.53
Chronic reactive oxygen species leading to human treatment-resistant gastric cancer Shihori Tanabe 1753: Chronic reactive oxygen species 1651: Treatment-resistant gastric cancer 1.58
Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response Takumi Ohishi 980: Inhibition, Calcineurin Activity 984: Impairment, T-cell dependent antibody response 1.38
Oxidative DNA damage leading to chromosomal aberrations and mutations Carole Yauk 1634: Increase, Oxidative damage to DNA 185: Increase, Mutations and 1636: Increase, Chromosomal aberrations 1.76
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation You Song 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92

Open for adoption

Title Point of Contact MIE AO OECD Project
Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Dries Knapen 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 Dries Knapen 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 Dries Knapen 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 Dries Knapen 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 Dries Knapen 279: Thyroperoxidase, Inhibition 351: Increased Mortality and 360: Decrease, Population trajectory 1.35

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 Marie-Gabrielle Zurich 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 Vinita Chauhan 1686: Direct Deposition of Energy 1556: Increase, lung cancer 1.56
Endocytic lysosomal uptake leading to liver fibrosis Marina Kuburic 1539: Endocytotic lysosomal uptake 344: N/A, Liver fibrosis 1.47
Reactive oxygen species generated from photoreactive chemicals leading to phototoxic reactions Satomi Onoue 1592: ROS generation from photoactivated chemicals 1599: Inflamatory events in light-exposed tissues 1.49
Substance interaction with the lung resident cell membrane components leading to lung fibrosis Sabina Halappanavar 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 Young Jun Kim 1617: 5α-reductase, inhibition 360: Decrease, Population trajectory 1.81
Inhibition of tyrosinase leads to decreased population in fish Young Jun Kim 1627: Inhibition of tyrosinase 360: Decrease, Population trajectory 1.78
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cell death You Song 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92

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Title Point of Contact MIE AO OECD Project
Inhibition of thyroid peroxidase leading to impaired fertility in fish June-Woo Park 279: Thyroperoxidase, Inhibition 78: Reduction, Cumulative fecundity and spawning 1.59
Lung surfactant function inhibition leading to decreased lung function Jorid Birkelund Sørli 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) Charles Wood 785: Activation, Androgen receptor 719: Increase, hepatocellular adenomas and carcinomas 1.26
Oxidation of iron in hemoglobin leading to hematotoxicity Mitchell S. Wilbanks 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

Not under active development

Title Point of Contact MIE AO OECD Project
Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage Barnett Rattner 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 Frazer Lowe 209: Peptide Oxidation 952: Hypertension 1.50
Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol Jun Kanno 245: Activation, PXR/SXR 2.5
PPARα activation leading to impaired fertility in adult male rodents Elise Grignard 227: Activation, PPARα 406: impaired, Fertility 1.21
Renal protein alkylation leading to kidney toxicity Angela Mally 244: Alkylation, Protein 814: Occurrence, Kidney toxicity 1.43
Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Katie Paul Friedman 239: Activation, Pregnane-X receptor, NR1l2 319: Loss, Cochlear function 1.9

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 Terje Svingen 1617: 5α-reductase, inhibition 1688: decrease, male anogenital distance 1.90
AhR activation leading to preeclampsia Sabrina Tait 18: Activation, AhR 1893: increase, Preeclampsia 1.42
Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring Terje Svingen 26: Antagonism, Androgen receptor 1688: decrease, male anogenital distance 1.90
Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE) Yasuharu Otsubo 1710: Binding to estrogen receptor (ER)-α in immune cells 1714: Exacerbation of systemic lupus erythematosus (SLE) 1.73
Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) Mathieu Vinken 41: Inhibition, Bile Salt Export Pump (ABCB11) 357: Cholestasis, Pathology 1.19
Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Terje Svingen 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 Andrea Hindman 1.79
EGFR Activation Leading to Decreased Lung Function Karsta Luettich 941: Activation, EGFR 1250: Decrease, Lung function 1.51
Frustrated phagocytosis-induced lung cancer Carole Seidel 1668: Frustrated phagoytosis 1670: Lung cancer 1.86
Increased DNA damage leading to increased risk of breast cancer Jessica Helm 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 Jessica Helm 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
Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response Yasuhiro Yoshida 1715: Inhibition of JAK3 1719: Impairment of T-cell dependent antibody response 1.74
Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Angela Mally 1481: Inhibition of mitochondrial DNA polymerase gamma (Pol gamma) 814: Occurrence, Kidney toxicity 1.43
Kidney dysfunction by decreased thyroid hormone Jung-Hwa Oh 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 Luigi Margiotta-Casaluci 1529: Blockade, L-Type Calcium Channels 1535: Heart failure 1.45
L-type calcium channel blockade leading to hypotension Luigi Margiotta-Casaluci 1.45
L-type calcium channel blockade leading to the disruption of cardiac electrophysiology Luigi Margiotta-Casaluci 1.45
Narcosis leading to respiratory failure Dries Knapen 46: Accumulation, Biological membranes 1.2
Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis Jinhee Choi 1270: Inactivation of PPARγ 1276: Lung fibrosis 1.54
PPARα activation leading to hepatocellular adenomas and carcinomas in rodents Chris Corton 227: Activation, PPARα 719: Increase, hepatocellular adenomas and carcinomas 1.17
Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity Angela Mally 1486: Binding of substrate, endocytic receptor 814: Occurrence, Kidney toxicity 1.43
Secretion of inflammatory cytokines after cellular sensing of the stressor leading to plaque progression Sarah Søs Poulsen 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 Hiroyuki Komatsu 1706: Stimulation, TLR7/8 1709: Psoriatic skin disease 1.75
Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Kevin Crofton 1656: Antagonism, Thyroid Receptor 402: Cognitive Function, Decreased 1.84
Trypsin inhibition leading to pancreatic acinar cell tumors Shigeru Hisada 1720: Trypsin inhibition 1725: Pancreatic acinar cell tumors 1.60
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased lipid storage You Song 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased lipid peroxidation You Song 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased protein oxidation You Song 1446: Decrease, Coupling of oxidative phosphorylation 1521: Decrease, Growth 1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via oxidative DNA damage You Song 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 Dan Villeneuve 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 Kristie Sullivan 396: Covalent Binding, Protein 313: Increase, Allergic Respiratory Hypersensitivity Response 1.20
Inhibition of retinaldehyde dehydrogenase leads to population decline Young Jun Kim 1637: Retinaldehyde dehydrogenase inhibition 360: Decrease, Population trajectory 1.77
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Kristie Sullivan 957: Binding, Transthyretin in serum 402: Cognitive Function, Decreased 1.41
Phospholipase A inhibitors lead to hepatotoxicity Jung-Hwa Oh 828: Inhibition, Phospholipase A 840: Formation, Liver fibrosis 1.39