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Showing 26 to 50 of 3158 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

3724	459: Increase, Liver steatosis	2405: Increase, Hepatocellular lipotoxicity	Feb 10, 2026	Feb 10, 2026	6 AOPs 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
3726	134: Increase, Kupffer cell activation	1489: Increase, Steatohepatitis	Feb 10, 2026	Feb 10, 2026	6 AOPs 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
3727	1489: Increase, Steatohepatitis	1271: Activation of TGF-β signaling	Feb 10, 2026	Feb 10, 2026	6 AOPs 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
3728	1271: Activation of TGF-β signaling	265: Increase, HSC activation	Feb 10, 2026	Feb 10, 2026	6 AOPs 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
3729	344: Increase, Liver fibrosis	2406: Increase, Regenerative nodule formation	Feb 10, 2026	Feb 10, 2026	6 AOPs 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
3730	2406: Increase, Regenerative nodule formation	2407: Increase, Cirrhosis	Feb 10, 2026	Feb 10, 2026	6 AOPs 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
67	55: Cell injury/death	134: Increase, Kupffer cell activation	Nov 29, 2016	Nov 29, 2016	6 AOPs 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
5	3: Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	219: Reduction, Plasma 17beta-estradiol concentrations	Nov 29, 2016	Mar 20, 2017	6 AOPs 7: Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female 25: Aromatase inhibition leading to reproductive dysfunction 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 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 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
359	386: Neuronal network function, Decreased	341: Impairment, Learning and memory	Nov 29, 2016	Jul 15, 2022	6 AOPs 90: Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 78: Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 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 13: Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 475: Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
2265	291: Accumulation, Triglyceride	459: Increase, Liver steatosis	Jan 15, 2021	Mar 27, 2024	6 AOPs 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 57: AhR activation leading to hepatic steatosis 591: DBDPE-induced DNA damage increase in liver leading to Non-alcoholic fatty liver disease via liver steatosis and inhibition of regeneration
2204	1771: Decrease, ATP pool	1821: Decrease, Cell proliferation	Nov 12, 2020	Dec 7, 2020	6 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) 601: Excessive reactive oxygen species leading to growth inhibition via fatty acid oxidation and reduced cell proliferation 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
748	758: Hippocampal Physiology, Altered	402: Cognitive function, decreased	Nov 29, 2016	Jul 26, 2024	6 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 134: Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 300: Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 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
3129	1392: Increase, Oxidative Stress	177: Increase, Mitochondrial dysfunction	Feb 17, 2024	May 31, 2024	6 AOPs 481: AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. 437: Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity 497: ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome 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 595: Emerging OPFRS reproductive outcome pathway
1910	155: Inadequate DNA repair	1635: Increase, DNA strand breaks	May 19, 2019	Jul 3, 2026	6 AOPs 296: Oxidative DNA damage leading to chromosomal aberrations and mutations 322: Alkylation of DNA leading to decreased sperm count 602: Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage 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 644: Bulky DNA adducts leading to chromosomal aberrations and mutations
1977	1686: Energy Deposition	1635: Increase, DNA strand breaks	Aug 26, 2019	Jul 29, 2024	6 AOPs 272: Deposition of energy leading to lung cancer 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 478: Deposition of energy leading to occurrence of cataracts 470: Deposition of energy leads to abnormal vascular remodeling 483: Deposition of Energy Leading to Learning and Memory Impairment
3032	2181: Angiogenesis dysfunction	2161: Increase, Vascular disrupting effects	Aug 28, 2023	Aug 28, 2023	5 AOPs 511: The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects 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 507: Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway 508: Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
3031	1928: increased，Vascular endothelial dysfunction	2181: Angiogenesis dysfunction	Aug 28, 2023	Aug 28, 2023	5 AOPs 511: The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects 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 507: Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway 508: Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
252	219: Reduction, Plasma 17beta-estradiol concentrations	285: Reduction, Vitellogenin synthesis in liver	Nov 29, 2016	Mar 20, 2017	5 AOPs 25: Aromatase inhibition leading to reproductive dysfunction 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 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 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
749	757: Hippocampal anatomy, Altered	758: Hippocampal Physiology, Altered	Nov 29, 2016	Jul 25, 2024	5 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 134: Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 300: Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 8: Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 442: Binding to voltage gate sodium channels during development leads to cognitive impairment
746	280: T4 in neuronal tissue, Decreased	756: Hippocampal gene expression, Altered	Nov 29, 2016	Aug 11, 2018	5 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 134: Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 8: Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 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
910	890: Degeneration of dopaminergic neurons of the nigrostriatal pathway	896: Parkinsonian motor deficits	Nov 29, 2016	Oct 3, 2025	5 AOPs 3: Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits 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 593: Redox cycling of a chemical by mitochondria leads to degeneration of nigrostriatal dopaminergic neurons
675	675: Reduced, Reproductive Success	360: Decrease, Population growth rate	Nov 29, 2016	Dec 3, 2016	5 AOPs 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 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
581	559: Activation, Nicotinic acetylcholine receptor	177: Increase, Mitochondrial dysfunction	Nov 29, 2016	Dec 3, 2016	5 AOPs 87: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure 77: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 80: Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure 79: Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure 78: Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1
643	619: Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)	626: Increased, serotonin (5-HT)	Nov 29, 2016	Dec 3, 2016	5 AOPs 98: 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation 195: 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase 97: 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline 204: 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase 203: 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
2212	1005: Reduced, Swimming performance	351: Increased Mortality	Nov 30, 2020	Sep 8, 2021	5 AOPs 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

Key Event Relationships (KERs)

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