AOP-Wiki

Title	Point of Contact	MIE	AO	OECD Project
Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations	Evgeniia Kazymova	Alkylation, DNA	Increase, Heritable mutations in offspring	1.11
Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Evgeniia Kazymova	Agonism, Androgen receptor	Decrease, Population growth rate	1.12
Antagonist binding to PPARα leading to body-weight loss	Agnes Aggy	Binding of antagonist, PPAR alpha	Decreased, Body Weight	2.3
Aromatase inhibition leading to reproductive dysfunction	Cataia Ives	Inhibition, Aromatase	Decrease, Population growth rate	1.12
Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Allie Always	Activation, AhR		1.27
Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Arthur Author	Activation, AhR	Increase, Early Life Stage Mortality	1.7
Aryl hydrocarbon receptor activation leading to uroporphyria	Allie Always	Activation, AhR	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	Binding of agonist, Ionotropic glutamate receptors	Impairment, Learning and memory	1.23
Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain	Cataia Ives	Binding at picrotoxin site, iGABAR chloride channel	Occurrence, Epileptic seizure	1.15
Chitin synthase 1 inhibition leading to mortality	Brendan Ferreri-Hanberry	Inhibition, Chitin synthase 1	Increase, Mortality	1.94
Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities	Agnes Aggy	Binding of antagonist, NMDA receptors	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	Binding of antagonist, NMDA receptors	N/A, Neurodegeneration Impairment, Learning and memory	1.13
Covalent Protein binding leading to Skin Sensitisation	Agnes Aggy	Covalent Binding, Protein	sensitisation, skin	1.1
Cyp2E1 Activation Leading to Liver Cancer	Agnes Aggy	Activation of Cyp2E1	Liver Cancer	1.24
Histone deacetylase inhibition leading to testicular atrophy	Brendan Ferreri-Hanberry	Histone deacetylase inhibition	Testicular atrophy	1.52
Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Arthur Author	Inhibition, Na+/I- symporter (NIS)	Impairment, Learning and memory	1.28
Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits	Cataia Ives	Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I)	Parkinsonian motor deficits	1.33
Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Evgeniia Kazymova	Thyroperoxidase, Inhibition	Cognitive Function, Decreased	1.10
Protein Alkylation leading to Liver Fibrosis	Brendan Ferreri-Hanberry	Alkylation, Protein	N/A, Liver fibrosis	1.14
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Allie Always	Decrease, Coupling of oxidative phosphorylation	Decrease, Growth	1.92

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

Title	Point of Contact	MIE	AO	OECD Project
Inhibitor binding to topoisomerase II leading to infant leukaemia	Andrea Terron	Binding to (interferes with) topoisomerase II enzyme	Infant leukaemia	1.53
Oxidative DNA damage leading to chromosomal aberrations and mutations	Brendan Ferreri-Hanberry	Increase, Oxidative damage to DNA	Increase, Mutations Increase, Chromosomal aberrations	1.76

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	Binding, Thiol/seleno-proteins involved in protection against oxidative stress	Impairment, Learning and memory	1.13
Deposition of energy leading to lung cancer	Brendan Ferreri-Hanberry	Deposition of Energy	Increase, lung cancer	1.56

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

Title	Point of Contact	MIE	AO	OECD Project
Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Allie Always	Acetylcholinesterase (AchE) Inhibition	Sensory axonal peripheral neuropathy Increased Mortality	1.2
AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)	Agnes Aggy	Formation, Pro-mutagenic DNA Adducts	Tumorigenesis, Hepatocellular carcinoma	1.8
Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female	Allie Always	reduction in ovarian granulosa cells, Aromatase (Cyp19a1)	impaired, Fertility irregularities, ovarian cycle	1.21
Chemical binding to tubulin in oocytes leading to aneuploid offspring	Cataia Ives	Binding, Tubulin	Increase, Aneuploid offspring	1.11
Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Brendan Ferreri-Hanberry	Activation, Constitutive androstane receptor	Increase, hepatocellular adenomas and carcinomas	1.17
Disruption of VEGFR Signaling Leading to Developmental Defects	Cataia Ives	Inhibition, VegfR2	Increased, Developmental Defects	1.6
Estrogen receptor antagonism leading to reproductive dysfunction	Evgeniia Kazymova	Antagonism, Estrogen receptor	Decrease, Population growth rate	1.12
Impaired IL-1R1 signaling leading to increased susceptibility to infection	Cataia Ives	Impaired IL-1R1 signaling	Increase, Increased susceptibility to infection	1.48
Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Cataia Ives	Decrease, Intracellular pH	Increase, Site of Contact Nasal Tumors	2.7
PPARα activation in utero leading to impaired fertility in males	Arthur Author	Activation, PPARα	impaired, Fertility Malformation, Male reproductive tract	1.21
Sustained AhR Activation leading to Rodent Liver Tumours	Allie Always	Activation, Long term AHR receptor driven direct and indirect gene expression changes	Formation, Hepatocellular and Bile duct tumors	1.7

Title	Point of Contact	MIE	AO	OECD Project
Chronic reactive oxygen species leading to human treatment-resistant gastric cancer	Agnes Aggy	Chronic reactive oxygen species	Treatment-resistant gastric cancer	1.58

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

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

Title	Point of Contact	MIE	AO	OECD Project
Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Evgeniia Kazymova	Binding to ACE2	Increased Mortality	1.96
Binding to ACE2 leading to lung fibrosis	Allie Always	Induced dysregulation of ACE2	Lung fibrosis	1.96
Inhibition of thyroid peroxidase leading to impaired fertility in fish	Cataia Ives	Thyroperoxidase, Inhibition	Reduction, Cumulative fecundity and spawning	1.59
Lung surfactant function inhibition leading to decreased lung function	Brendan Ferreri-Hanberry	Inhibition of lung surfactant function	Decrease, Lung function	1.87

Title	Point of Contact	MIE	AO	OECD Project
Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Evgeniia Kazymova	Activation, Androgen receptor	Increase, hepatocellular adenomas and carcinomas	1.26
Oxidation of iron in hemoglobin leading to hematotoxicity	Cataia Ives	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)	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	Activation, Pregnane-X receptor, NR1l2	Loss, Cochlear function	1.9

Title	Point of Contact	MIE	AO	OECD Project
Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage	Brendan Ferreri-Hanberry	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 Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin	Impaired recruitment , Population trajectory	1.31
Peptide Oxidation Leading to Hypertension	Brendan Ferreri-Hanberry	Peptide Oxidation	Hypertension	1.50
Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol	Brendan Ferreri-Hanberry	Activation, PXR/SXR		2.5
PPARα activation leading to impaired fertility in adult male rodents	Evgeniia Kazymova	Activation, PPARα	impaired, Fertility	1.21
Renal protein alkylation leading to kidney toxicity	Evgeniia Kazymova	Alkylation, Protein	Occurrence, Kidney toxicity	1.43

Title	Point of Contact	MIE	AO	OECD Project
5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Allie Always	5α-reductase, inhibition	decrease, male anogenital distance	1.90
AhR activation leading to preeclampsia	Agnes Aggy	Activation, AhR	increase, Preeclampsia	1.42
Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Evgeniia Kazymova	Antagonism, Androgen receptor	decrease, male anogenital distance	1.90
Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Allie Always	Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R)	Lung fibrosis	1.96
Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis	Cataia Ives	Binding to ACE2		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	Binding to ACE2	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	Binding to ACE2	Cerebrovascular disease (stroke)	1.96
Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption	Cataia Ives	Binding to ACE2		1.96
Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation	Arthur Author	Binding to ACE2	Viral infection and host-to-host transmission, proliferated	1.96
Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia	Agnes Aggy	Binding to ACE2	dysgeusia	1.96
Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Arthur Author	Binding to ACE2 SARS-CoV-2 cell entry Increased SARS-CoV-2 production	Thrombosis and Disseminated Intravascular Coagulation	1.96
Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)	Cataia Ives	Binding to estrogen receptor (ER)-α in immune cells	Exacerbation of systemic lupus erythematosus (SLE)	1.73
Bulky DNA adducts leading to mutations	Evgeniia Kazymova	Bulky DNA adducts, increase	Increase, Mutations	1.11
Chitinase inhibition leading to mortality	Evgeniia Kazymova	Inhibition, Chitinase	Increase, Mortality	1.94
Chitobiase inhibition leading to mortality	Cataia Ives	Inhibition, Chitobiase	Increase, Mortality	1.94
Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Arthur Author	Inhibition, Bile Salt Export Pump (ABCB11)	Cholestasis, Pathology	1.19
Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Cataia Ives	Fibrinolysis, decreased Bradykinin system, hyperactivated	Hyperinflammation	1.96
Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring	Cataia Ives		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	Activation, EGFR	Decrease, Lung function	1.51
Endothelial cell dysfunction leading to thromboinflammation	Arthur Author		Thromboinflammation, Increased	1.96
Frustrated phagocytosis-induced lung cancer	Arthur Author	Frustrated phagoytosis	Lung cancer	1.86
Increased DNA damage leading to increased risk of breast cancer	Allie Always	Increase, DNA damage	Increase, Mutations Increased, Ductal Hyperplasia N/A, Breast Cancer	1.80
Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Evgeniia Kazymova	Increase in reactive oxygen and nitrogen species (RONS)	Increase, DNA damage Increase, Mutations Increased, Ductal Hyperplasia N/A, Breast Cancer	1.80
Inhibition of 11β-hydroxylase leading to decresed population trajectory	Allie Always	11β-hydroxylase inhibition	Decrease, Population growth rate	1.93
Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory	Agnes Aggy	Inhibition of 11β-HSD	Decrease, Population growth rate	1.93
Inhibition of ALDH1A (RALDH) causing reduced all-trans retinoic acid levels leading to impaired fertility, females	Cataia Ives	Inhibition of ALDH1A (RALDH)	impaired, Fertility	1.97
Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis	Evgeniia Kazymova	Induced dysregulation of ACE2	N/A, Liver fibrosis	1.96
Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response	Brendan Ferreri-Hanberry	Inhibition of JAK3	Impairment of T-cell dependent antibody response	1.74
Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity	Agnes Aggy	Inhibition of mitochondrial DNA polymerase gamma (Pol gamma)	Occurrence, Kidney toxicity	1.43
Kidney dysfunction by decreased thyroid hormone	Arthur Author	Thyroid hormone synthesis, Decreased	Occurrence, Kidney toxicity	1.40
L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility	Arthur Author	Blockade, L-Type Calcium Channels	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	Accumulation, Biological membranes		1.2
Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis	Brendan Ferreri-Hanberry	Inactivation of PPARγ	Lung fibrosis	1.54
PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cataia Ives	Activation, PPARα	Increase, hepatocellular adenomas and carcinomas	1.17
Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity	Allie Always	Binding of substrate, endocytic receptor	Occurrence, Kidney toxicity	1.43
SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)	Arthur Author	Binding to ACE2	impaired olfactory function (anosmia)	1.96
Secretion of inflammatory cytokines after cellular sensing of the stressor leading to plaque progression	Arthur Author	Sensing of the stressor by pulmonary cells	Plaque progression in arteries	1.55
Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease	Evgeniia Kazymova	Stimulation, TLR7/8	Psoriatic skin disease	1.75
Sulfonylureareceptor binding leading to mortality	Arthur Author	Increase, Sulfonylurea receptor binding	Increase, Mortality	1.94
Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Evgeniia Kazymova	Antagonism, Thyroid Receptor	Cognitive Function, Decreased	1.84
Trypsin inhibition leading to pancreatic acinar cell tumors	Arthur Author	Trypsin inhibition	Pancreatic acinar cell tumors	1.60
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased lipid storage	Cataia Ives	Decrease, Coupling of oxidative phosphorylation	Decrease, Growth	1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased lipid peroxidation	Arthur Author	Decrease, Coupling of oxidative phosphorylation	Decrease, Growth	1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased protein oxidation	Agnes Aggy	Decrease, Coupling of oxidative phosphorylation	Decrease, Growth	1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via oxidative DNA damage	Brendan Ferreri-Hanberry	Decrease, Coupling of oxidative phosphorylation	Decrease, Growth	1.92

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

AOPs With OECD Status

WPHA/WNT Endorsed

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EAGMST Approved

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EAGMST Under Review

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Under Development

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Open for adoption

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