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Showing 1 to 25 of 1922 Key Events

ID	Title	Event Component Count	Biological Organization	Created At	Last Updated	AOPs

1392	Increase, Oxidative Stress Short Name Increase, Oxidative Stress	1	Molecular	May 30, 2017	Feb 11, 2026	68 AOPs 220: Cyp2E1 Activation Leading to Liver Cancer 17: 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 284: 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 377: Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) 411: Oxidative stress Leading to Decreased Lung Function 424: Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction 425: Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1 429: 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 452: Adverse outcome pathway of PM-induced respiratory toxicity 464: Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits 470: Deposition of energy leads to abnormal vascular remodeling 478: Deposition of energy leading to occurrence of cataracts 479: Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress 481: AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. 482: Deposition of energy leading to occurrence of bone loss 483: Deposition of Energy Leading to Learning and Memory Impairment 505: Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway 521: Essential element imbalance leads to reproductive failure via oxidative stress 26: Calcium-mediated neuronal ROS production and energy imbalance 488: Increased reactive oxygen species production leading to decreased cognitive function 396: Deposition of ionizing energy leads to population decline via impaired meiosis 437: Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity 535: Binding and activation of GPER leading to learning and memory impairments 171: Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat. 138: Organic anion transporter (OAT1) inhibition leading to renal failure and mortality 177: Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality 186: unknown MIE leading to renal failure and mortality 200: Estrogen receptor activation leading to breast cancer 444: Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability 447: Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways 476: Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity 497: ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome 457: Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine 459: AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 507: Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway 509: Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction 510: Demethylation of PPAR promotor leading to vascular disrupting effects 511: The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects 538: Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways 260: CYP2E1 activation and formation of protein adducts leading to neurodegeneration 450: Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality 501: Excessive iron accumulation leading to neurological disorders 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production 471: Neuron defect induced early behavioral change 31: Oxidation of iron in hemoglobin leading to hematotoxicity 534: Succinate dehydrogenase (SDH) inhibition leads to oxidative stress 462: Activation of reactive oxygen species leading the atherosclerosis 331: Reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 595: Emerging OPFRS reproductive outcome pathway 596: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell injury/death 598: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and reduced cell proliferation 599: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and cell injury/death 600: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell growth 601: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell proliferation 602: Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage 603: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell cycle disruption 608: Thyroid Hormone Excess Leading to Reduced, Swimming Performance via Hypomyelination 616: organic UV filter and its Photoproducts reproductive toxicity pathways 622: Calcineurin inhibitor induced nephrotoxicity leading to kidney failure 625: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated oxidative stress 628: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated oxidative stress 472: DNA adduct formation leading to kidney failure 642: Intestinal FXR inhibition leading to steatohepatitis via gut‑liver axis dysregulation 324: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell cycle disruption 325: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death 326: Reactive oxygen species leading to growth inhibition via lipid peroxidation and decreased cell proliferation 332: Reactive oxygen species leading to growth inhibition via protein oxidation and decreased cell proliferation 333: Reactive oxygen species leading to growth inhibition via protein oxidation and cell death
1115	Increase, Reactive oxygen species Short Name Increase, ROS	1	Cellular	Nov 29, 2016	Jun 12, 2025	62 AOPs 186: unknown MIE leading to renal failure and mortality 213: Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH) 303: Frustrated phagocytosis-induced lung cancer 383: Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis 382: Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis 384: Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease 396: Deposition of ionizing energy leads to population decline via impaired meiosis 409: Frustrated phagocytosis leads to malignant mesothelioma 413: Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure 416: Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway 418: Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway 386: Deposition of ionizing energy leading to population decline via inhibition of photosynthesis 387: Deposition of ionising energy leading to population decline via mitochondrial dysfunction 319: Binding to ACE2 leading to lung fibrosis 451: Interaction with lung resident cell membrane components leads to lung cancer 476: Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity 492: Glutathione conjugation leading to reproductive dysfunction via oxidative stress 497: ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome 500: Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis 505: Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway 513: Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway 521: Essential element imbalance leads to reproductive failure via oxidative stress 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production 462: Activation of reactive oxygen species leading the atherosclerosis 299: Deposition of energy leading to population decline via DNA oxidation and follicular atresia 311: Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis 331: Reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 327: Excessive reactive oxygen species production leading to mortality (1) 328: Excessive reactive oxygen species production leading to mortality (2) 329: Excessive reactive oxygen species production leading to mortality (3) 330: Excessive reactive oxygen species production leading to mortality (4) 26: Calcium-mediated neuronal ROS production and energy imbalance 534: Succinate dehydrogenase (SDH) inhibition leads to oxidative stress 273: Mitochondrial complex inhibition leading to liver injury 488: Increased reactive oxygen species production leading to decreased cognitive function 298: Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer 27: Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) 511: The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects 207: NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans 423: Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway 481: AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. 282: Adverse outcome pathway on photochemical toxicity initiated by light exposure 569: Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway 595: Emerging OPFRS reproductive outcome pathway 596: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell injury/death 598: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and reduced cell proliferation 599: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and cell injury/death 600: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell growth 601: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell proliferation 602: Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage 603: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell cycle disruption 608: Thyroid Hormone Excess Leading to Reduced, Swimming Performance via Hypomyelination 613: Peroxisome proliferator-activated receptor alpha activation leading to early life stage mortality via increased reactive oxygen species production 622: Calcineurin inhibitor induced nephrotoxicity leading to kidney failure 636: Increase in reactive oxygen species (ROS) leading to human amyotrophic lateral sclerosis (ALS) 638: Co-exposure to microplastics and cadmium leading to progression from NAFLD to liver tumorigenesis 472: DNA adduct formation leading to kidney failure 324: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell cycle disruption 325: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death 326: Reactive oxygen species leading to growth inhibition via lipid peroxidation and decreased cell proliferation 332: Reactive oxygen species leading to growth inhibition via protein oxidation and decreased cell proliferation 333: Reactive oxygen species leading to growth inhibition via protein oxidation and cell death
360	Decrease, Population growth rate Short Name Decrease, Population growth rate	1	Population	Nov 29, 2016	Jan 3, 2023	61 AOPs 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 25: Aromatase inhibition leading to reproductive dysfunction 29: Estrogen receptor agonism leading to reproductive dysfunction 30: Estrogen receptor antagonism leading to reproductive dysfunction 100: Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior 122: Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation 123: Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription 155: Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation 156: Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation 157: Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation 158: Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation 159: Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation 101: Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release 102: Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition 63: Cyclooxygenase inhibition leading to reproductive dysfunction 103: Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint 292: Inhibition of tyrosinase leads to decreased population in fish 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 16: Acetylcholinesterase inhibition leading to acute mortality 312: Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement 334: Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration 336: DNA methyltransferase inhibition leading to population decline (1) 337: DNA methyltransferase inhibition leading to population decline (2) 338: DNA methyltransferase inhibition leading to population decline (3) 339: DNA methyltransferase inhibition leading to population decline (4) 340: DNA methyltransferase inhibition leading to transgenerational effects (1) 341: DNA methyltransferase inhibition leading to transgenerational effects (2) 289: Inhibition of 5α-reductase leading to impaired fecundity in female fish 297: Inhibition of retinaldehyde dehydrogenase leads to population decline 346: Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation 363: Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure 349: Inhibition of 11β-hydroxylase leading to decresed population trajectory 348: Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory 376: Androgen receptor agonism leading to male-biased sex ratio 386: Deposition of ionizing energy leading to population decline via inhibition of photosynthesis 387: Deposition of ionising energy leading to population decline via mitochondrial dysfunction 388: Deposition of ionising energy leading to population decline via programmed cell death 389: Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis 364: Thyroperoxidase inhibition leading to altered visual function via decreased eye size 365: Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning 399: Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) 410: GSK3beta inactivation leading to increased mortality via defects in developing inner ear 216: Deposition of energy leading to population decline via DNA strand breaks and follicular atresia 238: Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis 299: Deposition of energy leading to population decline via DNA oxidation and follicular atresia 311: Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis 444: Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability 138: Organic anion transporter (OAT1) inhibition leading to renal failure and mortality 177: Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality 97: 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline 203: 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline 218: Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity 219: Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior 323: PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone 536: Estrogen receptor agonism leading to reduced survival and population growth due to renal failure 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production 564: DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity. 567: Binding to plastoquinone B site leading to decreased population growth rate via photosystem II inhibition 592: DBDPE-induced DNA strand breaks and LDH activity inhibition leading to population growth rate decline via energy metabolism disrupt and apoptosis 605: Thyroid Peroxidase Inhibition Leading to Reduced, Swimming Performance via Hypomyelination 608: Thyroid Hormone Excess Leading to Reduced, Swimming Performance via Hypomyelination
177	Increase, Mitochondrial dysfunction Short Name Increase, Mitochondrial dysfunction	1	Cellular	Nov 29, 2016	Feb 11, 2026	42 AOPs 48: Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. 77: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 78: Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 79: Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure 80: Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure 87: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure 3: Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits 144: Endocytic lysosomal uptake leading to liver fibrosis 178: Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure 200: Estrogen receptor activation leading to breast cancer 273: Mitochondrial complex inhibition leading to liver injury 377: Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) 437: Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity 423: Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway 479: Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress 480: Mitochondrial complexes inhibition leading to heart failure via decreased ATP production 481: AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. 509: Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction 511: The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects 256: Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity 258: Renal protein alkylation leading to kidney toxicity 464: Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits 500: Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis 205: AOP from chemical insult to cell death 335: AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment 362: Immune mediated hepatitis 130: Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity 497: ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome 34: LXR activation leading to hepatic steatosis 447: Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways 207: NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans 476: Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity 530: Endocytotic lysosomal uptake leads to intestinal barrier disruption 587: Inhibition of the mitochondrial complex III of nigro-striatal neurons leads to parkinsonian motor deficits 588: Inhibition of the mitochondrial complex II of nigro-striatal neurons leads to parkinsonian motor deficits 589: Inhibition of the mitochondrial complex IV of nigro-striatal neurons leads to parkinsonian motor deficits 595: Emerging OPFRS reproductive outcome pathway 622: Calcineurin inhibitor induced nephrotoxicity leading to kidney failure 624: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated mitochondrial dysfunction 627: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated mitochondrial dysfunction 636: Increase in reactive oxygen species (ROS) leading to human amyotrophic lateral sclerosis (ALS) 472: DNA adduct formation leading to kidney failure
55	Increase, Cell injury/death Short Name Cell injury/death	1	Cellular	Nov 29, 2016	May 27, 2024	29 AOPs 48: Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. 13: Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 38: Protein Alkylation leading to Liver Fibrosis 12: 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 144: Endocytic lysosomal uptake leading to liver fibrosis 17: 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 278: IKK complex inhibition leading to liver injury 281: Acetylcholinesterase Inhibition Leading to Neurodegeneration 273: Mitochondrial complex inhibition leading to liver injury 377: Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) 265: Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium 264: Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death 266: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity 268: Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling 479: Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress 490: Co-activation of IP3R and RyR leads to reduced IQ and increased socio-economic burden through non-cholinergic mechanisms 494: AhR activation leading to liver fibrosis 530: Endocytotic lysosomal uptake leads to intestinal barrier disruption 331: Reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 596: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell injury/death 599: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and cell injury/death 624: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated mitochondrial dysfunction 625: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated oxidative stress 626: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated endoplasmic reticulum stress 627: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated mitochondrial dysfunction 628: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated oxidative stress 629: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated endoplasmic reticulum stress 325: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death 333: Reactive oxygen species leading to growth inhibition via protein oxidation and cell death
351	Increased Mortality Short Name Increased Mortality	1	Population	Nov 29, 2016	Jul 8, 2022	28 AOPs 16: Acetylcholinesterase inhibition leading to acute mortality 96: Axonal sodium channel modulation leading to acute mortality 104: Altered ion channel activity leading impaired heart function 113: Glutamate-gated chloride channel activation leading to acute mortality 160: Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality 161: Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality 138: Organic anion transporter (OAT1) inhibition leading to renal failure and mortality 177: Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality 186: unknown MIE leading to renal failure and mortality 312: Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement 320: Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality 155: Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation 156: Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation 157: Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation 158: Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation 159: Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation 363: Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure 377: Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) 364: Thyroperoxidase inhibition leading to altered visual function via decreased eye size 365: Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning 399: Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) 413: Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure 410: GSK3beta inactivation leading to increased mortality via defects in developing inner ear 450: Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality 536: Estrogen receptor agonism leading to reduced survival and population growth due to renal failure 564: DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity. 605: Thyroid Peroxidase Inhibition Leading to Reduced, Swimming Performance via Hypomyelination 608: Thyroid Hormone Excess Leading to Reduced, Swimming Performance via Hypomyelination
281	Thyroxine (T4) in serum, Decreased Short Name T4 in serum, Decreased	1	Tissue	Nov 29, 2016	Oct 10, 2022	26 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 54: Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment 8: Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 65: XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 134: Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 152: Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity 159: Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation 175: Thyroperoxidase inhibition leading to altered amphibian metamorphosis 176: Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis 194: Hepatic nuclear receptor activation leading to altered amphibian metamorphosis 366: Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis 367: Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis 363: Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure 364: Thyroperoxidase inhibition leading to altered visual function via decreased eye size 365: Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning 119: Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) 110: Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) 162: Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse 128: Kidney dysfunction by decreased thyroid hormone 188: Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis 192: Pendrin inhibition leading to altered amphibian metamorphosis 193: Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis 457: Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine 458: AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 459: AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 605: Thyroid Peroxidase Inhibition Leading to Reduced, Swimming Performance via Hypomyelination
1521	Decrease, Growth Short Name Decrease, Growth	1	Individual	May 24, 2018	Jul 6, 2022	26 AOPs 263: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation 290: Mitochondrial ATP synthase antagonism leading to growth inhibition (1) 291: Mitochondrial ATP synthase antagonism leading to growth inhibition (2) 286: Mitochondrial complex III antagonism leading to growth inhibition (1) 287: Mitochondrial complex III antagonism leading to growth inhibition (2) 245: Reduction in photophosphorylation leading to growth inhibition in aquatic plants 265: Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium 264: Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death 266: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity 267: Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion 268: Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling 473: Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin 331: Reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 596: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell injury/death 598: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and reduced cell proliferation 599: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and cell injury/death 600: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell growth 602: Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage 603: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell cycle disruption 601: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell proliferation 567: Binding to plastoquinone B site leading to decreased population growth rate via photosystem II inhibition 324: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell cycle disruption 325: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death 326: Reactive oxygen species leading to growth inhibition via lipid peroxidation and decreased cell proliferation 332: Reactive oxygen species leading to growth inhibition via protein oxidation and decreased cell proliferation 333: Reactive oxygen species leading to growth inhibition via protein oxidation and cell death
18	Activation, AhR Short Name Activation, AhR	2	Molecular	Nov 29, 2016	May 31, 2025	22 AOPs 21: Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 57: AhR activation leading to hepatic steatosis 131: Aryl hydrocarbon receptor activation leading to uroporphyria 150: Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 151: AhR activation leading to preeclampsia 414: Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway 415: Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway 416: Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway 417: Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway 418: Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway 419: Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway 420: Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway 439: Activation of the AhR leading to metastatic breast cancer 455: Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development 456: Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity 458: AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 494: AhR activation leading to liver fibrosis 459: AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 563: Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis 578: AhR activation leading to cancer progression via immunosuppression 577: AhR activation leading to endometriosis
341	Impairment, Learning and memory Short Name Impairment, Learning and memory	2	Individual	Nov 29, 2016	Apr 27, 2026	22 AOPs 13: Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 48: Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. 54: Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment 77: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 78: Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 87: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure 88: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste 89: Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure 90: Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 12: 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 99: Histamine (H2) receptor antagonism leading to reduced survival 17: 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 475: Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons 483: Deposition of Energy Leading to Learning and Memory Impairment 490: Co-activation of IP3R and RyR leads to reduced IQ and increased socio-economic burden through non-cholinergic mechanisms 499: Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release 500: Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis 520: Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory 525: Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory 533: Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory 535: Binding and activation of GPER leading to learning and memory impairments 610: Decreased thyroid hormone levels in the brain regulated via transport, metabolism and TR activation leading to decreased cognition and motor function
277	Thyroid hormone synthesis, Decreased Short Name TH synthesis, Decreased	1	Cellular	Nov 29, 2016	Nov 4, 2022	21 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 65: XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 128: Kidney dysfunction by decreased thyroid hormone 134: Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 54: Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment 159: Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation 175: Thyroperoxidase inhibition leading to altered amphibian metamorphosis 176: Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis 188: Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis 192: Pendrin inhibition leading to altered amphibian metamorphosis 193: Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis 271: Inhibition of thyroid peroxidase leading to impaired fertility in fish 363: Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure 364: Thyroperoxidase inhibition leading to altered visual function via decreased eye size 365: Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning 119: Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) 110: Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) 402: Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain 457: Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine 459: AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 605: Thyroid Peroxidase Inhibition Leading to Reduced, Swimming Performance via Hypomyelination
563	Death/Failure, Colony Short Name Death/Failure, Colony	1	Population	Nov 29, 2016	Jun 7, 2018	21 AOPs 78: Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 79: Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure 80: Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure 82: Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure 84: Suppression of immune system contributes to impaired development and leads to colony loss/failure 85: Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure 86: Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure 87: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure 88: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste 89: Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure 90: Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 77: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 81: Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure 178: Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure 179: Varroa mite infestation increases virus levels leading to colony loss/failure 180: Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure 181: Weather event contributes to colony loss/failure 182: Weather event contributes abnormal foraging leading to colony loss/failure 183: Nosema infection increases energetic demands leading to colony loss/failure 184: Nosema infection causes abnormal role change that leads to colony loss/failure 185: Queen egg-laying decrease leads to colony loss/failure
459	Increase, Liver steatosis Short Name Increase, Liver steatosis	1	Organ	Nov 29, 2016	Feb 11, 2026	21 AOPs 58: NR1I3 (CAR) suppression leading to hepatic steatosis 60: NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis 61: NFE2L2/FXR activation leading to hepatic steatosis 62: AKT2 activation leading to hepatic steatosis 36: Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis 213: Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH) 285: Inhibition of N-linked glycosylation leads to liver injury 318: Glucocorticoid Receptor activation leading to hepatic steatosis 517: Pregnane X Receptor (PXR) activation leads to liver steatosis 518: Liver X Receptor (LXR) activation leads to liver steatosis 529: Xenobiotic binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism leading to liver steatosis 232: NFE2/Nrf2 repression to steatosis 57: AhR activation leading to hepatic steatosis 494: AhR activation leading to liver fibrosis 591: DBDPE-induced DNA damage increase in liver leading to Non-alcoholic fatty liver disease via liver steatosis and inhibition of regeneration 624: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated mitochondrial dysfunction 625: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated oxidative stress 626: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated endoplasmic reticulum stress 627: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated mitochondrial dysfunction 628: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated oxidative stress 629: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via lipogenesis-associated endoplasmic reticulum stress
1262	Apoptosis Short Name Apoptosis	1	Cellular	Feb 7, 2017	May 31, 2025	20 AOPs 205: AOP from chemical insult to cell death 207: NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans 212: Histone deacetylase inhibition leading to testicular atrophy 285: Inhibition of N-linked glycosylation leads to liver injury 419: Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway 439: Activation of the AhR leading to metastatic breast cancer 452: Adverse outcome pathway of PM-induced respiratory toxicity 393: AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation 476: Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity 460: Antagonism of Smoothened receptor leading to orofacial clefting 491: Decrease, GLI1/2 target gene expression leads to orofacial clefting 500: Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis 502: Decrease, cholesterol synthesis leads to orofacial clefting 441: Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation 535: Binding and activation of GPER leading to learning and memory impairments 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production 563: Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis 595: Emerging OPFRS reproductive outcome pathway 616: organic UV filter and its Photoproducts reproductive toxicity pathways 638: Co-exposure to microplastics and cadmium leading to progression from NAFLD to liver tumorigenesis
1771	Decrease, Adenosine triphosphate pool Short Name Decrease, ATP pool	1	Cellular	Apr 30, 2020	Jun 14, 2021	19 AOPs 328: Excessive reactive oxygen species production leading to mortality (2) 329: Excessive reactive oxygen species production leading to mortality (3) 264: Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death 263: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation 290: Mitochondrial ATP synthase antagonism leading to growth inhibition (1) 291: Mitochondrial ATP synthase antagonism leading to growth inhibition (2) 286: Mitochondrial complex III antagonism leading to growth inhibition (1) 287: Mitochondrial complex III antagonism leading to growth inhibition (2) 266: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity 331: Reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 596: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell injury/death 598: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and reduced cell proliferation 599: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and cell injury/death 600: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell growth 601: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell proliferation 612: Peroxisome proliferator-activated receptor alpha activation leading to early life stage mortality via reduced adenosine triphosphate 326: Reactive oxygen species leading to growth inhibition via lipid peroxidation and decreased cell proliferation 332: Reactive oxygen species leading to growth inhibition via protein oxidation and decreased cell proliferation 333: Reactive oxygen species leading to growth inhibition via protein oxidation and cell death
1686	Deposition of Energy Short Name Energy Deposition	1	Molecular	Aug 22, 2019	Aug 23, 2024	17 AOPs 272: Deposition of energy leading to lung cancer 432: Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia 386: Deposition of ionizing energy leading to population decline via inhibition of photosynthesis 387: Deposition of ionising energy leading to population decline via mitochondrial dysfunction 388: Deposition of ionising energy leading to population decline via programmed cell death 435: Deposition of ionising energy leads to population decline via pollen abnormal 216: Deposition of energy leading to population decline via DNA strand breaks and follicular atresia 238: Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis 311: Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis 299: Deposition of energy leading to population decline via DNA oxidation and follicular atresia 441: Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation 444: Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability 470: Deposition of energy leads to abnormal vascular remodeling 473: Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin 478: Deposition of energy leading to occurrence of cataracts 482: Deposition of energy leading to occurrence of bone loss 483: Deposition of Energy Leading to Learning and Memory Impairment
78	Reduction, Cumulative fecundity and spawning Short Name	1	Individual	Nov 29, 2016	Mar 20, 2017	17 AOPs 29: Estrogen receptor agonism leading to reproductive dysfunction 25: Aromatase inhibition leading to reproductive dysfunction 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 30: Estrogen receptor antagonism leading to reproductive dysfunction 122: Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation 123: Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription 271: Inhibition of thyroid peroxidase leading to impaired fertility in fish 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 289: Inhibition of 5α-reductase leading to impaired fecundity in female fish 216: Deposition of energy leading to population decline via DNA strand breaks and follicular atresia 238: Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis 299: Deposition of energy leading to population decline via DNA oxidation and follicular atresia 311: Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） 537: Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production 549: Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
1821	Decrease, Cell proliferation Short Name Decrease, Cell proliferation	1	Cellular	Nov 12, 2020	Dec 7, 2020	16 AOPs 263: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation 290: Mitochondrial ATP synthase antagonism leading to growth inhibition (1) 286: Mitochondrial complex III antagonism leading to growth inhibition (1) 399: Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) 460: Antagonism of Smoothened receptor leading to orofacial clefting 267: Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion 491: Decrease, GLI1/2 target gene expression leads to orofacial clefting 502: Decrease, cholesterol synthesis leads to orofacial clefting 591: DBDPE-induced DNA damage increase in liver leading to Non-alcoholic fatty liver disease via liver steatosis and inhibition of regeneration 598: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and reduced cell proliferation 602: Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage 603: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell cycle disruption 601: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell proliferation 324: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell cycle disruption 326: Reactive oxygen species leading to growth inhibition via lipid peroxidation and decreased cell proliferation 332: Reactive oxygen species leading to growth inhibition via protein oxidation and decreased cell proliferation
350	Increase, Mortality Short Name Increase, Mortality	1	Individual	Nov 29, 2016	Oct 26, 2020	16 AOPs 327: Excessive reactive oxygen species production leading to mortality (1) 328: Excessive reactive oxygen species production leading to mortality (2) 329: Excessive reactive oxygen species production leading to mortality (3) 358: Chitinase inhibition leading to mortality 359: Chitobiase inhibition leading to mortality 360: Chitin synthase 1 inhibition leading to mortality 361: Sulfonylureareceptor binding leading to mortality 465: Alcohol dehydrogenase leading to reproductive dysfunction 466: Doda decarboxylase leading to mortality 467: Knickkopf leading to mortality 471: Neuron defect induced early behavioral change 330: Excessive reactive oxygen species production leading to mortality (4) 4: Ecdysone receptor agonism leading to mortality via suppression of Ftz-f1 342: Ecdysone receptor hyperactivation leading to mortality via mis-timed activation of nuclear receptor cascade 343: Ecdysone receptor antagonism leading to mortality via mis-timed ecdysone receptor-responsive nuclear receptor cascade 606: Ecdysone receptor antagonism leading to mortality via inhibition of chitin synthase 1
1446	Decrease, Coupling of oxidative phosphorylation Short Name Decrease, Coupling of OXPHOS	3	Cellular	Jun 29, 2017	Nov 7, 2025	15 AOPs 267: Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion 263: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation 264: Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death 265: Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium 266: Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity 268: Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling 534: Succinate dehydrogenase (SDH) inhibition leads to oxidative stress 331: Reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 596: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell injury/death 598: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and reduced cell proliferation 612: Peroxisome proliferator-activated receptor alpha activation leading to early life stage mortality via reduced adenosine triphosphate 613: Peroxisome proliferator-activated receptor alpha activation leading to early life stage mortality via increased reactive oxygen species production 326: Reactive oxygen species leading to growth inhibition via lipid peroxidation and decreased cell proliferation 332: Reactive oxygen species leading to growth inhibition via protein oxidation and decreased cell proliferation 333: Reactive oxygen species leading to growth inhibition via protein oxidation and cell death
1739	Binding to ACE2 Short Name Binding to ACE2	1	Molecular	Mar 2, 2020	Oct 21, 2024	15 AOPs 320: Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality 374: 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 381: Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia 385: Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation 394: SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia) 395: Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke) 406: SARS-CoV-2 infection leading to hyperinflammation 407: SARS-CoV-2 infection leading to pyroptosis 426: SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction. 427: ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure. 422: Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption 428: Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis 430: Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation 379: Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation 468: Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
402	Cognitive function, decreased Short Name Cognitive function, decreased	2	Individual	Nov 29, 2016	Jul 25, 2024	15 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 65: XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 134: Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 152: Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity 300: Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 405: Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function 485: Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition 486: Binding to the extracellular protein laminin leading to decreased cognitive function 487: Unknown MIE altering cholesterol metabolism leading to decreased cognition 488: Increased reactive oxygen species production leading to decreased cognitive function 489: Inhibition of voltage-gated sodium channels leading to decreased cognition 458: AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 459: AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals 442: Binding to voltage gate sodium channels during development leads to cognitive impairment 581: Glucocorticoid receptor (GR) activation during development leads to cognitive function (COG) decrease
286	Altered, Transcription of genes by the androgen receptor Short Name	1	Tissue	Nov 29, 2016	Mar 20, 2026	14 AOPs 19: Androgen receptor antagonism leading to adverse effects in the male foetus (mammals) 307: Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring 344: Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring 345: Androgen receptor (AR) antagonism leading to decreased fertility in females 305: 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring 495: Androgen receptor activation leading to prostate cancer 306: Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） 372: Androgen receptor antagonism leading to testicular cancer 570: Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring 571: 5α-reductase inhibition leading to hypospadias in male (mammalian) offspring 575: Decreased testosterone synthesis leading to increased nipple retention (NR) in male (rodent) offspring 576: 5α-reductase inhibition leading to increased nipple retention (NR) in male (rodent) offspring 477: Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring
406	decreased, Fertility Short Name decreased, Fertility	2	Individual	Nov 29, 2016	Dec 17, 2024	13 AOPs 7: Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female 51: PPARα activation leading to impaired fertility in adult male rodents 18: PPARα activation in utero leading to impaired fertility in males 64: Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility 348: Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory 349: Inhibition of 11β-hydroxylase leading to decresed population trajectory 396: Deposition of ionizing energy leads to population decline via impaired meiosis 398: Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia 492: Glutathione conjugation leading to reproductive dysfunction via oxidative stress 345: Androgen receptor (AR) antagonism leading to decreased fertility in females 592: DBDPE-induced DNA strand breaks and LDH activity inhibition leading to population growth rate decline via energy metabolism disrupt and apoptosis 400: Inhibition of CYP26B1 activity in fetal testis leading to reduced fertility 640: Activation, estrogen receptor alpha leads to decreased fertility via prolonged estrus cycle
386	Decrease of neuronal network function Short Name Neuronal network function, Decreased	1	Organ	Nov 29, 2016	May 28, 2018	13 AOPs 13: Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 78: Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 90: Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 54: Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment 17: 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 405: Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function 429: 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 501: Excessive iron accumulation leading to neurological disorders 475: Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons 522: Estrogen antagonism leading to increased risk of autism-like behavior 533: Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory 610: Decreased thyroid hormone levels in the brain regulated via transport, metabolism and TR activation leading to decreased cognition and motor function 636: Increase in reactive oxygen species (ROS) leading to human amyotrophic lateral sclerosis (ALS)