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

926	Oxidation, Glutathione (To be considered with MIE) Short Name Oxidation, Glutathione	1	Molecular	Nov 29, 2016	Nov 9, 2017	2 AOPs 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 413: Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
1287	Glutathione synthesis Short Name Glutathione synthesis	1	Cellular	Feb 15, 2017	Sep 16, 2017	209: Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
1290	Glutathione homeostasis Short Name Glutathione homeostasis	1	Cellular	Feb 15, 2017	Sep 16, 2017	209: Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP

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

130	Depletion, GSH Short Name Depletion, GSH	1	Cellular	Nov 29, 2016	Sep 14, 2023	492: Glutathione conjugation leading to reproductive dysfunction via oxidative stress
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
209	Peptide Oxidation Short Name Peptide Oxidation	1	Molecular	Nov 29, 2016	Nov 13, 2017	4 AOPs 27: Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) 108: Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat) 149: Peptide Oxidation Leading to Hypertension 210: Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
373	Formation, Pro-mutagenic DNA Adducts Short Name Formation, Pro-mutagenic DNA Adducts	1	Molecular	Nov 29, 2016	Sep 16, 2017	2 AOPs 46: AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC) 472: DNA adduct formation leading to kidney failure
380	Activation, Pre-MIE: Metabolism of AFB1 Short Name Activation, Pre-MIE: Metabolism of AFB1	0	Molecular	Nov 29, 2016	Nov 29, 2016	None
384	Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci Short Name	0		Nov 29, 2016	Nov 29, 2016	None
396	Covalent Binding, Protein Short Name Covalent Binding, Protein	1	Molecular	Nov 29, 2016	Nov 5, 2020	2 AOPs 40: Covalent Protein binding leading to Skin Sensitisation 39: Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
397	Response, Keratinocytes Short Name Response, Keratinocytes	0	Cellular	Nov 29, 2016	Nov 29, 2016	None
409	Metabolism of AFB1, Production of Reactive Electrophiles Short Name	1	Molecular	Nov 29, 2016	Sep 16, 2017	46: AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
423	Increased, Clonal Expansion / Cell Proliferation to Form Pre-Neoplastic Altered Hepatic Foci Short Name	0		Nov 29, 2016	Nov 29, 2016	None
429	Cellular Proliferation and Clonal Expansion of Mutant Cells (Pre-neoplastic Foci), Alteration of cellular growth homeostasis Short Name	0		Nov 29, 2016	Nov 29, 2016	None
491	Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF) Short Name	1	Organ	Nov 29, 2016	Sep 16, 2017	46: AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
826	Activation, Keratinocytes Short Name Activation, Keratinocytes	2	Cellular	Nov 29, 2016	Sep 16, 2017	40: Covalent Protein binding leading to Skin Sensitisation
898	Disruption, Lysosome Short Name Disruption, Lysosome	1	Cellular	Nov 29, 2016	Aug 29, 2024	3 AOPs 257: Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity 144: Endocytic lysosomal uptake leading to liver fibrosis 530: Endocytotic lysosomal uptake leads to intestinal barrier disruption
926	Oxidation, Glutathione (To be considered with MIE) Short Name Oxidation, Glutathione	1	Molecular	Nov 29, 2016	Nov 9, 2017	2 AOPs 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 413: Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
927	KE1 : S-Glutathionylation, eNOS Short Name S-Glutathionylation, eNOS	2	Molecular	Nov 29, 2016	Nov 20, 2017	149: Peptide Oxidation Leading to Hypertension
944	dimerization, AHR/ARNT Short Name dimerization, AHR/ARNT	2	Molecular	Nov 29, 2016	May 31, 2025	7 AOPs 150: Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF 21: Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 151: AhR activation leading to preeclampsia 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 563: Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis
1000	stabilization, PPAR alpha co-repressor Short Name stabilization, PPAR alpha co-repressor	2	Molecular	Nov 29, 2016	Apr 30, 2019	6: Antagonist binding to PPARα leading to body-weight loss
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 332: Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell growth 331: Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 326: Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation and reduced cell proliferation 333: Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation 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 324: Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation and cell death 325: Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation and reduced cell growth 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
1171	Increase, Clonal Expansion of Altered Hepatic Foci Short Name	0	Cellular	Nov 29, 2016	Jan 6, 2021	37: PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
1391	Activation of Cyp2E1 Short Name Activation of Cyp2E1	0	Molecular	May 30, 2017	Jun 19, 2021	2 AOPs 220: Cyp2E1 Activation Leading to Liver Cancer 450: Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
1392	Increase, Oxidative Stress Short Name Increase, Oxidative Stress	1	Molecular	May 30, 2017	Feb 11, 2026	67 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 324: Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation and cell death 325: Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation and reduced cell growth 326: Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation and reduced cell proliferation 331: Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death 332: Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell growth 333: Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation 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
1487	Binding, Thiol/seleno-proteins involved in protection against oxidative stress Short Name	0	Molecular	Nov 9, 2017	Jul 15, 2022	2 AOPs 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
1498	Loss of alveolar capillary membrane integrity Short Name	0	Tissue	Jan 3, 2018	May 17, 2023	2 AOPs 173: Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis 302: Lung surfactant function inhibition leading to decreased lung function
1508	CYP2E1 Activation Short Name CYP2E1 Activation	0	Molecular	Mar 26, 2018	Apr 9, 2018	260: CYP2E1 activation and formation of protein adducts leading to neurodegeneration