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
  • 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

Open for comment. Do not cite

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

EAGMST Approved

Open for comment. Do not cite

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

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
  • 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

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
  • 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

EAGMST Under Review

Open for citation & comment

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

Open for comment. Do not cite

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

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
  • 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

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
  • 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

Open for comment. Do not cite

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

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
  • 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

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
  • 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

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
  • 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

Under Development: Contributions and Comments Welcome

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