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Showing 26 to 50 of 3131 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

351	376: Increased, Induced Mutations in Critical Genes	384: Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci	Nov 29, 2016	Nov 29, 2016	None
350	384: Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci	378: Tumorigenesis, Hepatocellular carcinoma	Nov 29, 2016	Dec 3, 2016	None
336	307: Increase, Vitellogenin synthesis in liver	220: Increase, Plasma vitellogenin concentrations	Nov 29, 2016	Jun 24, 2024	3 AOPs 29: Estrogen receptor agonism leading to reproductive dysfunction 536: Estrogen receptor agonism leading to reduced survival and population growth due to renal failure 537: Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
347	52: Decreased, Calcium influx	381: BDNF, Reduced	Nov 29, 2016	Jun 13, 2018	2 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 13: Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
346	376: Increased, Induced Mutations in Critical Genes	378: Tumorigenesis, Hepatocellular carcinoma	Nov 29, 2016	Nov 30, 2016	1 AOP 46: AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
345	373: Formation, Pro-mutagenic DNA Adducts	378: Tumorigenesis, Hepatocellular carcinoma	Nov 29, 2016	Nov 29, 2016	1 AOP 46: AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
344	373: Formation, Pro-mutagenic DNA Adducts	377: Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H	Nov 29, 2016	Dec 3, 2016	None
343	377: Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H	378: Tumorigenesis, Hepatocellular carcinoma	Nov 29, 2016	Nov 29, 2016	None
342	376: Increased, Induced Mutations in Critical Genes	377: Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered H	Nov 29, 2016	Nov 29, 2016	None
340	380: Activation, Pre-MIE: Metabolism of AFB1	373: Formation, Pro-mutagenic DNA Adducts	Nov 29, 2016	Dec 3, 2016	None
338	310: Alteration, Wnt pathway	240: Feminisation or incomplete development, Primary and accessory male sex organs	Nov 29, 2016	Dec 3, 2016	1 AOP 19: Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
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
45	36: Inhibition, Aromatase	3: Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Nov 29, 2016	Nov 30, 2016	1 AOP 25: Aromatase inhibition leading to reproductive dysfunction
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
77	66: Activation, ChREBP	89: Synthesis, De Novo Fatty Acid (FA)	Nov 29, 2016	Dec 3, 2016	1 AOP 34: LXR activation leading to hepatic steatosis
70	60: Induction, Chitin degradation and resorption	238: Induction, Pre-mature molting	Nov 29, 2016	Dec 3, 2016	None
69	57: Proliferation, Cell proliferation in the absence of cytotoxicity	142: Hyperplasia, Hyperplasia	Nov 29, 2016	Dec 3, 2016	1 AOP 1: Uncharacterized liver damage leading to hepatocellular carcinoma
68	55: Cell injury/death	265: Increase, HSC activation	Nov 29, 2016	Apr 21, 2026	2 AOPs 38: Protein Alkylation leading to Liver Fibrosis 494: AhR activation leading to liver fibrosis
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
66	54: Up Regulation, CD36	115: Increase, FA influx	Nov 29, 2016	Mar 27, 2024	2 AOPs 34: LXR activation leading to hepatic steatosis 517: Pregnane X Receptor (PXR) activation leads to liver steatosis
62	52: Decreased, Calcium influx	341: Impairment, Learning and memory	Nov 29, 2016	Dec 3, 2016	None
61	51: Inhibition, Ca++ ATPase	50: Increase, Ca++ (intracellular)	Nov 29, 2016	Dec 3, 2016	1 AOP 26: Calcium-mediated neuronal ROS production and energy imbalance
60	50: Increase, Ca++ (intracellular)	178: Mitochondrial electron transport chain, disrupted	Nov 29, 2016	Dec 3, 2016	1 AOP 26: Calcium-mediated neuronal ROS production and energy imbalance
59	49: Reduction, Ca and HCO3 transport to shell gland	106: Reduction, Eggshell thickness	Nov 29, 2016	Dec 3, 2016	1 AOP 28: Cyclooxygenase inhibition leading reproductive failure
51	39: Increased Cholinergic Signaling	360: Decrease, Population growth rate	Nov 29, 2016	Dec 3, 2016	None

Key Event Relationships (KERs)

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