Recently added AOPs

Title Point of Contact MIE AO
Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis Evgeniia Kazymova
  • Increase, Oxygen-evolving complex damage
  • Decrease, Reproduction
  • Decrease, Population growth rate
Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway Brendan Ferreri-Hanberry
5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation Allie Always
  • Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)
  • Increased, predation
A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Brendan Ferreri-Hanberry
  • Memory Loss
ACE2 binding to viral S-protein leading to microvascular disfunction via ACE2 dysregulation Brendan Ferreri-Hanberry
  • Binding to ACE2
ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure. Evgeniia Kazymova
  • Binding to ACE2
  • Heart failure
Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​ Allie Always
  • Acetylcholinesterase (AchE) Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
Acetylcholinesterase Inhibition Leading to Neurodegeneration Allie Always
  • Acetylcholinesterase (AchE) Inhibition
  • N/A, Neurodegeneration
Adverse outcome pathway of PM-induced respiratory toxicity Cataia Ives
  • Non-coding RNA expression profile alteration
  • Chronic obstructive pulmonary disease
AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals Cataia Ives
AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals Brendan Ferreri-Hanberry
AhR activation leads to increased diabetes risk Arthur Author
  • Activation, AhR
  • Increased diabetes risk
Alkylation of DNA leading to reduced sperm count Brendan Ferreri-Hanberry
  • Alkylation, DNA
  • Reduce, Sperm count
Androgen receptor (AR) antagonism leading to decreased fertility in females Cataia Ives
  • Antagonism, Androgen receptor
  • Decreased fertility, Reduced number of oocytes ovulated
Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring Evgeniia Kazymova
  • Antagonism, Androgen receptor
  • Nipple retention in male offspring, increased
Androgen receptor agonism leading to male-biased sex ratio Evgeniia Kazymova
  • Agonism, Androgen receptor
  • Decrease, Population growth rate
Androgen receptor antagonism leading to testicular cancer Brendan Ferreri-Hanberry
  • Antagonism, Androgen receptor
  • Testicular Cancer
Antagonist binding to smoothened causes disruption of shh signaling resulting in orofacial clefting Arthur Author
  • Antagonism, Smoothened receptor
AOP for thyroid disorder caused by triphenyl phosphate Brendan Ferreri-Hanberry
AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment Arthur Author
  • Mitochondrial impairment
  • Urothelial Tumor
Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation Brendan Ferreri-Hanberry
  • Inhibition, Aromatase
  • Decrease, Population growth rate
Aryl hydrocarbon receptor activation leading to early stage mortality via cardiovascular toxicity Allie Always
  • Activation, AhR
  • Increase, Early Life Stage Mortality
Aryl hydrocarbon receptor activation leading to early stage mortality via impeded craniofacial development Agnes Aggy
  • Activation, AhR
  • Increase, Early Life Stage Mortality
Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway Arthur Author
Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway Agnes Aggy
  • Decrease, Lung function
Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway Brendan Ferreri-Hanberry
  • Activation, AhR
  • Lung cancer
Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway Cataia Ives
  • Activation, AhR
  • Lung cancer
Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway Allie Always
  • Activation, AhR
Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway Evgeniia Kazymova
  • Activation, AhR
  • Lung fibrosis
Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway Allie Always
  • Activation, AhR
Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease Brendan Ferreri-Hanberry
  • Binding, Thiol/seleno-proteins involved in protection against oxidative stress
  • Chronic kidney disease
Ceramide synthase inhibition leading to neural tube defects Agnes Aggy
  • Inhibition of Ceramide Synthase
combined unhealthy lifestyle factors leading to metabolic syndrome Evgeniia Kazymova
Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis Arthur Author
  • Binding, Thyroid binding globulin in serum
  • Altered, Amphibian metamorphosis
Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Brendan Ferreri-Hanberry
  • Binding, Transthyretin in serum
  • Altered, Amphibian metamorphosis
CYP26 inhibition leading to disturbed dorsal lateral hinge point bending which causes neural tube closure defects Cataia Ives
CYP2E1 activation and formation of protein adducts leading to neurodegeneration Brendan Ferreri-Hanberry
  • CYP2E1 Activation
  • Protein Adduct Formation
  • Neurodegeneration
Cytochrome oxidase inhibition leading to olfactory nasal lesions Agnes Aggy
  • Inhibition, cytochrome oxidase
  • Increase, Site of Contact Nasal Tumors
Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia Allie Always
  • Deposition of Energy
  • Acute Myeloid Leukemia
Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Agnes Aggy
  • Deposition of Energy
  • Reduction, Cumulative fecundity and spawning
  • Decrease, Population growth rate
Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Agnes Aggy
  • Deposition of Energy
  • Reduction, Cumulative fecundity and spawning
  • Decrease, Population growth rate
Deposition of ionising energy leading to population decline via programmed cell death Allie Always
  • Deposition of Energy
  • Decrease, Reproduction
  • Decrease, Population growth rate
Deposition of ionising energy leading to population decline via mitochondrial dysfunction Agnes Aggy
  • Deposition of Energy
  • Decrease, Reproduction
  • Decrease, Population growth rate
Deposition of ionising energy leads to population decline via impaired oogenesis and spermatogenesis Agnes Aggy
Deposition of ionising energy leads to population decline via pollen abnormal Brendan Ferreri-Hanberry
  • Deposition of Energy
  • Decrease, Reproduction
  • Decreased, Population trajectory
Deposition of ionizing energy leads to leading to population decline via inhibition of photosynthesis Arthur Author
  • Deposition of Energy
  • Decrease, Reproduction
  • Decrease, Population growth rate
Deposition of ionizing energy leads to population decline via impaired meiosis Allie Always
  • Deposition of Ionizing Energy
  • Increased, Reactive oxygen species
  • Increase, DNA damage
  • Decrease of egg production and cummulative fecundity
  • Decrease, Reproduction
  • Decreased, Population size
DNA damage and mutations leading to Metastatic Breast Cancer Agnes Aggy
  • Increased, DNA damage and mutation
  • metastatic breast cancer
DNA methyltransferase inhibition leading to population decline (3) Evgeniia Kazymova
  • Increase, DNA methyltransferase inhibition
  • Decrease, Fecundity
  • Decrease, Population growth rate
Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Cataia Ives
  • Prolonged TLR9 activation
  • Multi Organ Failure involving Acute Respiratory Distress Syndrome
  • Increased Mortality
Dysregulated underperforming Toll Like Receptors (TLRs) leading to high pathogen load Brendan Ferreri-Hanberry
  • Toll Like Receptor (TLR) Dysregulation
Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development Allie Always
Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity Evgeniia Kazymova
Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Arthur Author
  • Activation, AhR
  • Reduction, Cumulative fecundity and spawning
  • Decrease, Population growth rate
Estrogen Receptor Alpha Agonism leads to Impaired Reproduction Evgeniia Kazymova
  • Activation, estrogen receptor alpha
  • Impaired, Reproduction
Excessive reactive oxygen species production leading to mortality (1) Cataia Ives
  • Increase, Reactive Oxygen Species production
  • Increase, Mortality
Excessive reactive oxygen species production leading to mortality (2) Brendan Ferreri-Hanberry
  • Increase, Reactive Oxygen Species production
  • Increase, Mortality
Excessive reactive oxygen species production leading to mortality (3) Arthur Author
  • Increase, Reactive Oxygen Species production
  • Increase, Mortality
Excessive reactive oxygen species production leading to mortality (4) Agnes Aggy
  • Increase, Reactive Oxygen Species production
  • Increase, Mortality
Formation of DNA photoproducts leading to growth inhibition (1) Allie Always
  • Increase, Formation of DNA photoproducts
  • Increase, Mortality
Formation of DNA photoproducts leading to growth inhibition (2) Evgeniia Kazymova
Formation of DNA photoproducts leading to growth inhibition (3) Cataia Ives
From activation of the AhR leading to breast cancer related death Evgeniia Kazymova
  • Activation, AhR
  • N/A, Breast Cancer
Frustrated phagocytosis leads to malignant mesothelioma Evgeniia Kazymova
  • Frustrated phagoytosis
  • Increased, mesotheliomas
G protein-coupled estrogen receptor 1 (GPER) signal pathway in the endocrine disrupting effect Agnes Aggy
Glucocorticoid Receptor activation leading to hepatic steatosis Agnes Aggy
  • Activation, Glucocorticoid Receptor
  • Increased, Liver Steatosis
Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility Allie Always
  • Activation, Glucocorticoid Receptor
  • Increased, Disease susceptibility
Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration Brendan Ferreri-Hanberry
  • Activation, Glucocorticoid Receptor
  • Decrease, Population growth rate
GSK3beta inactivation leading to increased mortality via defects in developing inner ear Cataia Ives
  • GSK3beta inactivation
  • Increased Mortality
  • Decrease, Population growth rate
hERG inhibition leading to cardiac toxicity Evgeniia Kazymova
  • Binding to hERG channel
  • hERG channel biogenesis interference
  • Sudden cardiac death
Histone deacetylase inhibition leads to impeded craniofacial development Agnes Aggy
  • Histone deacetylase inhibition
  • Facial cartilage structures are reduced in size and morphologically distorted
Histone deacetylase inhibition leads to neural tube defects Allie Always
  • Histone deacetylase inhibition
  • Neural tube defects
Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease Cataia Ives
  • Hyperactivation of ACE/Ang-II/AT1R axis
  • Chronic kidney disease
Hypothalamic estrogen receptors inhibition leading to ovarian cancer Cataia Ives
  • Suppression, Estrogen receptor (ER) activity
  • Promotion, ovarian adenomas
  • Promotion, ovarian granular cell tumors
IKK complex inhibition leading to liver injury Brendan Ferreri-Hanberry
  • Inhibition, IKK complex
  • Necrotic Tissue
  • Liver Injury
Imbalance in redox homeostasis leading to structural damage to tissues Allie Always
Immune mediated hepatitis Agnes Aggy
  • benzoquinone imine and acylglucuronide metabolites
  • Immune mediated hepatitis
Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males Arthur Author
  • Increased (ectopic) all-trans retinoic acid concentration
  • Reduce, Sperm count
Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM) Agnes Aggy
  • Increase, TNF
  • Gestational diabetes mellitus
Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) Evgeniia Kazymova
  • Inhibition, Cytochrome P450 enzyme (CYP17A1) activity
  • Malformation, cryptorchidism - maldescended testis
Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome Evgeniia Kazymova
  • Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I)
  • Chemical induced Fanconi syndrome
Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis Cataia Ives
  • Inhibition of cystathionine beta-synthase
  • Impaired,anterior-posterior axis development
Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) Brendan Ferreri-Hanberry
  • Inhibition of Fyna
  • Increased Mortality
  • Decrease, Population growth rate
Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity Brendan Ferreri-Hanberry
  • Thiol group of chemicals interact with sulfuhydryl groups of proteins to form thiol adducts
  • Growth, reduction
  • Decreased, survival
Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity Agnes Aggy
  • Inhibition, Mitochondrial Electron Transport Chain Complexes
  • Occurrence, Kidney toxicity
Inhibition of N-linked glycosylation leads to liver injury Arthur Author
  • Inhibition of N-linked glycosylation
  • Liver Injury
Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries Arthur Author
  • Inhibition of ALDH1A (RALDH)
  • transposition of the great arteries
Inhibition of voltage gate sodium channels leading to impairment in learning and memory during development Arthur Author
  • Inhibit, voltage-gated sodium channel
  • Impairment, Learning and memory
Interaction with lung resident cell membrane components leads to lung cancer Evgeniia Kazymova
  • Substance interaction with the lung resident cell membrane components
  • Lung cancer
Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Allie Always
  • Deposition of Energy
  • Increase in reactive oxygen and nitrogen species (RONS)
  • Increase, DNA damage
  • Decrease, Population growth rate
Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation Brendan Ferreri-Hanberry
  • Deposition of Energy
  • Increase risk, microcephaly
Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways Brendan Ferreri-Hanberry
  • Increased, Kidney Failure
Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis Cataia Ives
  • Activation, Latent Transforming Growth Factor Beta 1
  • Pulmonary fibrosis
Luteinizing hormone receptor antagonism leading to reproductive dysfunction Brendan Ferreri-Hanberry
  • Antagonism,LH receptor
  • Decline, Population trajectory
Metabolic Syndrome leading to Toll Like Receptor dysregulation Cataia Ives
Microtubule interacting drugs lead to peripheral neuropathy Arthur Author
  • Binding of microtubule stabilizing agents (MSA) to microtubules
  • Sensory axonal peripheral neuropathy
Mitochondrial complex inhibition leading to liver injury Arthur Author
  • Increase, Mitochondrial complex III antagonism
  • Mitochondrial Complex IV inhibition
  • Mitochondrial Complex V inhibition
  • Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I)
  • Inhibition, NADH-ubiquinone oxidoreductase (complex I)
  • Binding of inhibitor to mitochondrial complex III
  • Binding of inhibitor to mitochondrial complex IV
  • Binding of inhibitor to mitochondrial complex V
  • Necrotic Tissue
  • Liver Injury
Mitochondrial dysfunction to metabolic diseases Arthur Author
Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function Brendan Ferreri-Hanberry
  • Acetylcholinesterase (AchE) Inhibition
  • Cognitive Function, Decreased
Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure Agnes Aggy
  • Oxidation, Glutathione (To be considered with MIE)
  • Increased Mortality
Oxidative stress Leading to Decreased Lung Function Brendan Ferreri-Hanberry
  • Oxidative Stress
  • Decrease, Lung function
Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction Arthur Author
  • Oxidative Stress
  • Decrease, Lung function
Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1 Agnes Aggy
  • Oxidative Stress
  • Decrease, Lung function
Photosystem II antagonism leading to growth inhibition via dysregulation of growth hormone Cataia Ives
Photosystem II antagonism leading to growth inhibition via oxidative damage Allie Always
Photosystem II antagonism leading to growth inhibition via suppression of photosynthesis Evgeniia Kazymova
PM-related Adverse outcome pathway frameworks on various systems Cataia Ives
PM2.5-related AOP frameworks on liver diseases Arthur Author
PPARalpha Agonism Impairs Fish Reproduction Arthur Author
  • Activation, PPARα
PPARG activation leading to intrahepatic cholestasis Evgeniia Kazymova
Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population Brendan Ferreri-Hanberry
reactive oxygen species generation leading to increased cardiovascular morbidity and mortality Allie Always
Reduced environmental pH leading to thinner shells in Mytilus edulis Cataia Ives
Reduction in photophosphorylation leading to growth inhibition in aquatic plants Arthur Author
  • Increase, Uncoupling of photophosphorylation
  • Decrease, Growth
ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality Arthur Author
S-adenosylmethionine depletion leading to population decline (1) Agnes Aggy
  • Inhibition, Chitin synthase 1
  • Increase, Mortality
S-adenosylmethionine depletion leading to population decline (2) Allie Always
  • Increase, Sulfonylurea receptor binding
  • Increase, Mortality
SARS-CoV-2 infection leading to hyperinflammation Arthur Author
  • Binding to ACE2
  • Hyperinflammation
SARS-CoV-2 infection leading to pyroptosis Agnes Aggy
  • Binding to ACE2
  • Pyroptosis
SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction. Allie Always
  • Binding to ACE2
  • Myocardial Infarction
Sensitization induction of the intestinal tract by food proteins Cataia Ives
Superoxide dismutase inhibition leading to increased insulin resistance Evgeniia Kazymova
TBX1 inhibition leading to congenital cardiac conotruncal anomalies Agnes Aggy
  • Inhibition, TBX1
  • Anomalies, Congenital cardiac conotruncal
test AOP Allie Always
Thermal stress leading to population decline (1) Agnes Aggy
  • N/A, Mitochondrial dysfunction 1
  • Decrease, Fecundity
  • Decrease, Population growth rate
Thermal stress leading to population decline (2) Allie Always
  • N/A, Mitochondrial dysfunction 1
  • Decrease, Fecundity
  • Decrease, Population growth rate
Thermal stress leading to population decline (3) Evgeniia Kazymova
  • N/A, Mitochondrial dysfunction 1
  • Decrease, Fecundity
  • Decrease, Population growth rate
Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain Allie Always
Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Cataia Ives
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Allie Always
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
Thyroperoxidase inhibition leading to altered visual function via decreased eye size Evgeniia Kazymova
  • Thyroperoxidase, Inhibition
  • Increased Mortality
  • Decrease, Population growth rate
Toll-like receptor 4 (TLR4) activation leads to neurodegeneration via increase in neuroinflammation Arthur Author
  • Toll like receptor 4 Activation
  • N/A, Neurodegeneration (updated)
Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis Arthur Author
  • Toll-like receptor 4 activation
  • Inactivation of PPARγ
  • Pulmonary fibrosis
XYZ leading to ABC Arthur Author
α-diketone-induced bronchiolitis obliterans Agnes Aggy
  • Interaction of α-diketones with arginine residues
  • Bronchiolitis obliterans