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Showing 3101 to 3125 of 3130 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

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
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
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
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
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
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
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
315	285: Reduction, Vitellogenin synthesis in liver	221: Reduction, Plasma vitellogenin concentrations	Nov 29, 2016	Mar 20, 2017	7 AOPs 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 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
312	281: T4 in serum, Decreased	280: T4 in neuronal tissue, Decreased	Nov 29, 2016	Apr 4, 2019	7 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 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 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
3632	1392: Increase, Oxidative Stress	1767: Increase, Protein oxidation	Sep 8, 2025	Sep 8, 2025	7 AOPs 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 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 603: Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell cycle disruption 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
1386	219: Reduction, Plasma 17beta-estradiol concentrations	221: Reduction, Plasma vitellogenin concentrations	Mar 17, 2017	Oct 18, 2018	7 AOPs 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 25: Aromatase inhibition leading to reproductive dysfunction 271: Inhibition of thyroid peroxidase leading to impaired fertility in fish 289: Inhibition of 5α-reductase leading to impaired fecundity in female fish 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） 549: Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
972	18: Activation, AhR	944: dimerization, AHR/ARNT	Nov 29, 2016	Mar 22, 2018	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
2270	961: Increased, Clearance of thyroxine from serum	281: T4 in serum, Decreased	Jan 26, 2021	Jan 26, 2021	7 AOPs 152: Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity 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 162: Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse 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
2056	1739: Binding to ACE2	1738: SARS-CoV-2 cell entry	Mar 2, 2020	Oct 21, 2024	7 AOPs 320: Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality 394: SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia) 406: SARS-CoV-2 infection leading to hyperinflammation 422: Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption 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)
309	279: Thyroperoxidase, Inhibition	277: TH synthesis, Decreased	Nov 29, 2016	Nov 4, 2022	8 AOPs 42: Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals 159: Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation 271: Inhibition of thyroid peroxidase leading to impaired fertility in fish 175: Thyroperoxidase inhibition 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)
295	265: Increase, HSC activation	68: Increase, Collagen accumulation	Nov 29, 2016	Dec 5, 2018	8 AOPs 38: Protein Alkylation leading to Liver Fibrosis 144: Endocytic lysosomal uptake leading to liver fibrosis 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
164	155: Inadequate DNA repair	185: Increase, Mutations	Nov 29, 2016	Mar 8, 2024	8 AOPs 15: Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations 141: Alkylation of DNA leading to cancer 2 139: Alkylation of DNA leading to cancer 1 296: Oxidative DNA damage leading to chromosomal aberrations and mutations 272: Deposition of energy leading to lung cancer 397: Bulky DNA adducts leading to mutations 443: DNA damage and mutations leading to Metastatic Breast Cancer 478: Deposition of energy leading to occurrence of cataracts
82	68: Increase, Collagen accumulation	344: Increase, Liver fibrosis	Nov 29, 2016	Dec 5, 2018	8 AOPs 38: Protein Alkylation leading to Liver Fibrosis 144: Endocytic lysosomal uptake leading to liver fibrosis 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
2168	281: T4 in serum, Decreased	1101: Altered, Amphibian metamorphosis	Aug 25, 2020	Aug 25, 2020	8 AOPs 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 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
2203	1446: Decrease, Coupling of OXPHOS	1771: Decrease, ATP pool	Nov 12, 2020	Jul 6, 2022	9 AOPs 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 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 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
2767	55: Cell injury/death	1521: Decrease, Growth	Sep 27, 2022	Sep 27, 2022	9 AOPs 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 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 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
337	309: Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	78: Reduction, Cumulative fecundity and spawning	Nov 29, 2016	Mar 20, 2017	9 AOPs 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 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） 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
255	221: Reduction, Plasma vitellogenin concentrations	309: Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	Nov 29, 2016	Mar 20, 2017	9 AOPs 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 25: Aromatase inhibition leading to reproductive dysfunction 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 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） 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
2205	1821: Decrease, Cell proliferation	1521: Decrease, Growth	Nov 12, 2020	Jul 6, 2022	10 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) 267: Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion 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
2124	1614: Decrease, AR activation	286: Altered, Transcription of genes by the AR	May 11, 2020	Mar 20, 2026	10 AOPs 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 306: Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring 307: Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring 570: Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring 571: 5α-reductase inhibition leading to hypospadias in male (mammalian) offspring 576: 5α-reductase inhibition leading to increased nipple retention (NR) in male (rodent) offspring 575: Decreased testosterone synthesis leading to increased nipple retention (NR) in male (rodent) offspring 477: Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring

Key Event Relationships (KERs)

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