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 Carole Yauk
  • Alkylation, DNA
  • Increase, Heritable mutations in offspring
1.11
Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Dan Villeneuve
  • Agonism, Androgen receptor
  • Decrease, Population growth rate
1.12
Antagonist binding to PPARα leading to body-weight loss Kurt A. Gust
  • Binding of antagonist, PPAR alpha
  • Decreased, Body Weight
2.3
Aromatase inhibition leading to reproductive dysfunction Dan Villeneuve
  • Inhibition, Aromatase
  • Decrease, Population growth rate
1.12
Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 Markus Hecker
  • Activation, AhR
1.27
Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Amani Farhat
  • Activation, AhR
  • Increase, Early Life Stage Mortality
1.7
Aryl hydrocarbon receptor activation leading to uroporphyria Amani Farhat
  • 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. Anna Price
  • 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 Ping Gong
  • Binding at picrotoxin site, iGABAR chloride channel
  • Occurrence, Epileptic seizure
1.15
Chitin synthase 1 inhibition leading to mortality Simon Schmid
  • 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 Anna Price
  • 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 Florianne Tschudi-Monnet
  • Binding of antagonist, NMDA receptors
  • N/A, Neurodegeneration
  • Impairment, Learning and memory
1.13
Covalent Protein binding leading to Skin Sensitisation Sharon Munn
  • Covalent Binding, Protein
  • sensitisation, skin
1.1
Cyp2E1 Activation Leading to Liver Cancer Francina Webster
  • Activation of Cyp2E1
  • Liver Cancer
1.24
Histone deacetylase inhibition leading to testicular atrophy Shihori Tanabe
  • Histone deacetylase inhibition
  • Testicular atrophy
1.52
Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Anna Price
  • 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 Andrea Terron
  • Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I)
  • Parkinsonian motor deficits
1.33
Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Kevin Crofton
  • Thyroperoxidase, Inhibition
  • Cognitive Function, Decreased
1.10
Protein Alkylation leading to Liver Fibrosis Brigitte Landesmann
  • Alkylation, Protein
  • N/A, Liver fibrosis
1.14
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation You Song
  • Decrease, Coupling of oxidative phosphorylation
  • Decrease, Growth
1.92

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
Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response Takumi Ohishi
  • Inhibition, Calcineurin Activity
  • Impairment, T-cell dependent antibody response
1.38

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
  • Binding, Thiol/seleno-proteins involved in protection against oxidative stress
  • Impairment, Learning and memory
1.13

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 Dries Knapen
  • Inhibition, Deiodinase 1
  • Increased Mortality
  • Decrease, Population growth rate
1.35
Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Dries Knapen
  • Inhibition, Deiodinase 1
  • Increased Mortality
  • Decrease, Population growth rate
1.35
Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Dries Knapen
  • Inhibition, Deiodinase 2
  • Increased Mortality
  • Decrease, Population growth rate
1.35
Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Dries Knapen
  • Inhibition, Deiodinase 2
  • Increased Mortality
  • Decrease, Population growth rate
1.35
Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Dries Knapen
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
1.35

EAGMST Approved

Open for comment. Do not cite

Title Point of Contact MIE AO OECD Project
Oxidative DNA damage leading to chromosomal aberrations and mutations Carole Yauk
  • 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
Deposition of energy leading to lung cancer Vinita Chauhan
  • Deposition of Energy
  • Increase, lung cancer
1.56

EAGMST Under Review

Open for citation & comment

Title Point of Contact MIE AO OECD Project
AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC) Ted Simon
  • Formation, Pro-mutagenic DNA Adducts
  • Tumorigenesis, Hepatocellular carcinoma
1.8
Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Elise Grignard
  • reduction in ovarian granulosa cells, Aromatase (Cyp19a1)
  • impaired, Fertility
  • irregularities, ovarian cycle
1.21
Chemical binding to tubulin in oocytes leading to aneuploid offspring Francesco Marchetti
  • Binding, Tubulin
  • Increase, Aneuploid offspring
1.11
Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat Kristin Lichti-Kaiser
  • Activation, Constitutive androstane receptor
  • Increase, hepatocellular adenomas and carcinomas
1.17
Disruption of VEGFR Signaling Leading to Developmental Defects Tom Knudsen
  • Inhibition, VegfR2
  • Increased, Developmental Defects
1.6
Estrogen receptor antagonism leading to reproductive dysfunction Dan Villeneuve
  • Antagonism, Estrogen receptor
  • Decrease, Population growth rate
1.12
Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response Takao Ashikaga
  • Impaired IL-1R1 signaling in T cell
  • Impairment of TDAR
1.48
Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors Justin Teeguarden
  • Decrease, Intracellular pH
  • Increase, Site of Contact Nasal Tumors
2.7
PPARα activation in utero leading to impaired fertility in males Elise Grignard
  • Activation, PPARα
  • impaired, Fertility
  • Malformation, Male reproductive tract
1.21
Sustained AhR Activation leading to Rodent Liver Tumours Rick Becker
  • Activation, Long term AHR receptor driven direct and indirect gene expression changes
  • Formation, Hepatocellular and Bile duct tumors
1.7
Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Lucia Vergauwen
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
1.35

Open for comment. Do not cite

Title Point of Contact MIE AO OECD Project
Increases in cellular reactive oxygen species (Chronic reactive oxygen species) leading to human treatment-resistant gastric cancer Shihori Tanabe
  • Increases in cellular reactive oxygen species
  • 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 Satomi Onoue
  • ROS generation from photoactivated chemicals
  • Inflamatory events in light-exposed tissues
1.49
Endocytic lysosomal uptake leading to liver fibrosis Marina Kuburic
  • Endocytotic lysosomal uptake
  • N/A, Liver fibrosis
1.47
Substance interaction with the lung resident cell membrane components leading to lung fibrosis Sabina Halappanavar
  • 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 Young Jun Kim
  • 5α-reductase, inhibition
  • Decrease, Population growth rate
1.81
Inhibition of tyrosinase leads to decreased population in fish Young Jun Kim
  • Inhibition of tyrosinase
  • Decrease, Population growth rate
1.78
Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death You Song
  • 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 Young Jun Kim
  • Binding to ACE2
  • Increased Mortality
1.96
Binding to ACE2 leading to lung fibrosis Young Jun Kim
  • Induced dysregulation of ACE2
  • Lung fibrosis
1.96
Inhibition of thyroid peroxidase leading to impaired fertility in fish June-Woo Park
  • Thyroperoxidase, Inhibition
  • Reduction, Cumulative fecundity and spawning
1.59
Lung surfactant function inhibition leading to decreased lung function Jorid Birkelund Sørli
  • 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) Charles Wood
  • Activation, Androgen receptor
  • Increase, hepatocellular adenomas and carcinomas
1.26
Oxidation of iron in hemoglobin leading to hematotoxicity Mitchell S. Wilbanks
  • 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 Katie Paul Friedman
  • 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 Barnett Rattner
  • 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 Frazer Lowe
  • Peptide Oxidation
  • Hypertension
1.50
Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol Jun Kanno
  • Activation, PXR/SXR
2.5
PPARα activation leading to impaired fertility in adult male rodents Elise Grignard
  • Activation, PPARα
  • impaired, Fertility
1.21
Renal protein alkylation leading to kidney toxicity Angela Mally
  • 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 Terje Svingen
  • 5α-reductase, inhibition
  • decrease, male anogenital distance
1.90
AhR activation leading to preeclampsia Sabrina Tait
  • Activation, AhR
  • increase, Preeclampsia
1.42
Alcohol Induced DNA damage and mutations leading to Metastatic Breast Cancer Usha Adiga
  • Increased, DNA damage and mutation
  • metastatic breast cancer
1.103
Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring Terje Svingen
  • Antagonism, Androgen receptor
  • decrease, male anogenital distance
1.90
Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Young Jun Kim
  • 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 Laure-Alix Clerbaux
  • 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 Anna Price
  • 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) Magda Sachana
  • Binding to ACE2
  • Cerebrovascular disease (stroke)
1.96
Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption Laure-Alix Clerbaux
  • Binding to ACE2
1.96
Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation Sally Mayasich
  • Binding to ACE2
  • Viral infection and host-to-host transmission, proliferated
1.96
Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia Young Jun Kim
  • Binding to ACE2
  • dysgeusia
1.96
Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation Shihori Tanabe
  • Binding to ACE2
  • Thrombosis and Disseminated Intravascular Coagulation
1.96
Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE) Yasuharu Otsubo
  • Binding to estrogen receptor (ER)-α in immune cells
  • Exacerbation of systemic lupus erythematosus (SLE)
1.73
Bulky DNA adducts leading to mutations Carole Yauk
  • Bulky DNA adducts, increase
  • Increase, Mutations
1.11
Chitinase inhibition leading to mortality Simon Schmid
  • Inhibition, Chitinase
  • Increase, Mortality
1.94
Chitobiase inhibition leading to mortality Simon Schmid
  • Inhibition, Chitobiase
  • Increase, Mortality
1.94
Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) Mathieu Vinken
  • Inhibition, Bile Salt Export Pump (ABCB11)
  • Cholestasis, Pathology
1.19
Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation Penny Nymark
  • Fibrinolysis, decreased
  • Bradykinin system, hyperactivated
  • Hyperinflammation
1.96
Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Terje Svingen
  • 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
  • Activation, EGFR
  • Decrease, Lung function
1.51
Endothelial cell dysfunction leading to thromboinflammation Luigi Margiotta-Casaluci
  • Thromboinflammation, Increased
1.96
Frustrated phagocytosis-induced lung cancer Carole Seidel
  • Frustrated phagocytosis
  • Lung cancer
1.86
Hypothalamic estrogen receptors inhibition leading to ovarian cancer Kalyan Gayen
  • Suppression, Estrogen receptor (ER) activity
  • Promotion, ovarian adenomas
  • Promotion, ovarian granular cell tumors
1.104
Increased DNA damage leading to increased risk of breast cancer Jessica Helm
  • 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 Jessica Helm
  • 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 Young Jun Kim
  • 11β-hydroxylase inhibition
  • Decrease, Population growth rate
1.93
Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory Young Jun Kim
  • 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 Terje Svingen
  • Inhibition of ALDH1A (RALDH)
  • impaired, Fertility
1.97
Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis Young Jun Kim
  • Induced dysregulation of ACE2
  • N/A, Liver fibrosis
1.96
Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response Yasuhiro Yoshida
  • Inhibition of JAK3
  • Impairment of T-cell dependent antibody response
1.74
Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Angela Mally
  • Inhibition of mitochondrial DNA polymerase gamma (Pol gamma)
  • Occurrence, Kidney toxicity
1.43
Inhibition of voltage gate sodium channels leading to impairment in learning and memory during development Andrea Terron
  • Inhibit, voltage-gated sodium channel
  • Impairment, Learning and memory
1.91
Kidney dysfunction by decreased thyroid hormone Jung-Hwa Oh
  • Thyroid hormone synthesis, Decreased
  • Occurrence, Kidney toxicity
1.40
L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility Luigi Margiotta-Casaluci
  • Blockade, L-Type Calcium Channels
  • 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
  • Accumulation, Biological membranes
1.2
Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis Jinhee Choi
  • Inactivation of PPARγ
  • Lung fibrosis
1.54
PPARα activation leading to hepatocellular adenomas and carcinomas in rodents Chris Corton
  • Activation, PPARα
  • Increase, hepatocellular adenomas and carcinomas
1.17
Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity Angela Mally
  • 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) Sandra Coecke
  • Binding to ACE2
  • impaired olfactory function (anosmia)
1.96
Secretion of inflammatory cytokines after cellular sensing of the stressor leading to plaque progression Sarah Søs Poulsen
  • 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 Hiroyuki Komatsu
  • Stimulation, TLR7/8
  • Psoriatic skin disease
1.75
Sulfonylureareceptor binding leading to mortality Simon Schmid
  • Increase, Sulfonylurea receptor binding
  • Increase, Mortality
1.94
Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Kevin Crofton
  • Antagonism, Thyroid Receptor
  • Cognitive Function, Decreased
1.84
Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Lucia Vergauwen
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
1.35
Thyroperoxidase inhibition leading to altered visual function via decreased eye size Lucia Vergauwen
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
1.35
Trypsin inhibition leading to pancreatic acinar cell tumors Shigeru Hisada
  • Trypsin inhibition
  • Pancreatic acinar cell tumors
1.60
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity You Song
  • Decrease, Coupling of oxidative phosphorylation
  • Decrease, Growth
1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion You Song
  • Decrease, Coupling of oxidative phosphorylation
  • Decrease, Growth
1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium You Song
  • Decrease, Coupling of oxidative phosphorylation
  • Decrease, Growth
1.92
Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling You Song
  • 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 Dan Villeneuve
  • 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 Kristie Sullivan
  • Covalent Binding, Protein
  • Increase, Allergic Respiratory Hypersensitivity Response
1.20
Inhibition of retinaldehyde dehydrogenase leads to population decline Young Jun Kim
  • Retinaldehyde dehydrogenase inhibition
  • Decrease, Population growth rate
1.77
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Kristie Sullivan
  • Binding, Transthyretin in serum
  • Cognitive Function, Decreased
1.41
Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity Jung-Hwa Oh
  • Inhibition, Phospholipase A
  • Formation, Liver fibrosis
1.39