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

79	Inhibition, Cyclooxygenase activity Short Name Inhibition, Cyclooxygenase activity	2	Molecular	Nov 29, 2016	Sep 16, 2017	6 AOPs 28: Cyclooxygenase inhibition leading reproductive failure 100: Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior 101: Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release 103: Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint 63: Cyclooxygenase inhibition leading to reproductive dysfunction 102: Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
110	Impairment, Endothelial network Short Name Impairment, Endothelial network	1	Cellular	Nov 29, 2016	Jan 18, 2022	2 AOPs 43: Disruption of VEGFR Signaling Leading to Developmental Defects 150: Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
201	Binding of antagonist, NMDA receptors Short Name Binding of antagonist, NMDA receptors	0	Molecular	Nov 29, 2016	Jun 13, 2018	2 AOPs 13: Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 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
276	Up Regulation, TGFbeta1 expression Short Name Up Regulation, TGFbeta1 expression	1	Cellular	Nov 29, 2016	Sep 16, 2017	None
301	Binding, VEGF-A Short Name Binding, VEGF-A	0		Nov 29, 2016	Nov 29, 2016	None
304	Decreased, VegfR2 Short Name Decreased, VegfR2	0		Nov 29, 2016	Nov 29, 2016	None
352	N/A, Neurodegeneration Short Name N/A, Neurodegeneration	1	Tissue	Nov 29, 2016	Feb 23, 2021	7 AOPs 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 48: Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. 281: Acetylcholinesterase Inhibition Leading to Neurodegeneration 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 450: Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality 500: Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis 471: Neuron defect induced early behavioral change
768	Increase, Cytotoxicity Short Name Increase, Cytotoxicity	2	Cellular	Nov 29, 2016	Sep 16, 2017	3 AOPs 108: Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat) 136: Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors 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
846	Accumulation, Highly carboxylated porphyrins Short Name	1	Organ	Nov 29, 2016	May 7, 2018	131: Aryl hydrocarbon receptor activation leading to uroporphyria
902	Inflammation, Liver Short Name Inflammation, Liver	1	Organ	Nov 29, 2016	Sep 16, 2017	2 AOPs 377: Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) 615: Suppression of Keap1 cysteine oxidation leading to liver inflammation
981	Reduction, NFAT/AP-1 complex formation Short Name Reduction, NFAT/AP-1 complex formation	2	Cellular	Nov 29, 2016	Jun 27, 2021	154: Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
982	Suppression, Suppression in mixed lymphocyte reaction (MLR) Short Name	0	Cellular	Nov 29, 2016	Dec 3, 2016	None
1101	Altered, Amphibian metamorphosis Short Name Altered, Amphibian metamorphosis	2	Organ	Nov 29, 2016	Sep 2, 2020	11 AOPs 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 189: Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis 190: Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis 191: Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis 192: Pendrin inhibition leading to altered amphibian metamorphosis 193: Dual oxidase (DUOX) 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
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
1202	Suppression, IL-2 and IL-4 production Short Name Suppression, IL-2 and IL-4 production	2	Cellular	Nov 29, 2016	Jun 27, 2021	154: Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
1203	Suppression, Suppression of production of cytotoxic T-cells Short Name	0	Tissue	Nov 29, 2016	Dec 3, 2016	None
1269	Increase, COX-2 expression Short Name Increase, COX-2 expression	1	Molecular	Feb 9, 2017	Mar 20, 2018	21: Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
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
1500	Increased, fibroblast proliferation and myofibroblast differentiation Short Name	0	Tissue	Jan 5, 2018	May 17, 2023	173: Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
1572	Impaired IL-1 signaling Short Name Impaired IL-1 signaling	0	Molecular	Dec 24, 2018	Jun 24, 2019	None
1634	Increase, Oxidative DNA damage Short Name Increase, Oxidative DNA damage	1	Molecular	May 19, 2019	Oct 8, 2024	6 AOPs 296: Oxidative DNA damage leading to chromosomal aberrations and mutations 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 478: Deposition of energy leading to occurrence of cataracts 330: Excessive reactive oxygen species production leading to mortality (4) 602: Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage
1753	Chronic reactive oxygen species Short Name Chronic ROS	1	Molecular	Mar 23, 2020	Jun 12, 2025	None
1939	Viral infection and host-to-host transmission, proliferated Short Name Viral infection, proliferated	1	Individual	Oct 24, 2021	Jun 29, 2024	430: Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
2068	Increase, Endothelial Dysfunction Short Name Increase, Endothelial Dysfunction	1	Tissue	Sep 28, 2022	Aug 26, 2024	2 AOPs 470: Deposition of energy leads to abnormal vascular remodeling 462: Activation of reactive oxygen species leading the atherosclerosis
2118	Succinate dehydrogenase, inhibited Short Name SDH, inhibited	3	Molecular	Apr 3, 2023	May 4, 2023	5 AOPs 457: Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine 534: Succinate dehydrogenase (SDH) inhibition leads to oxidative stress 474: Succinate dehydrogenase inactivation leads to cancer by promoting EMT 546: Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms 588: Inhibition of the mitochondrial complex II of nigro-striatal neurons leads to parkinsonian motor deficits

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