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Showing 3076 to 3100 of 3158 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

1676	709: Increase, Cytotoxicity (renal tubular cell)	814: Occurrence, Kidney toxicity	Oct 25, 2017	Mar 8, 2022	4 AOPs 256: Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity 257: Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity 258: Renal protein alkylation leading to kidney toxicity 437: Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
747	756: Hippocampal gene expression, Altered	757: Hippocampal anatomy, Altered	Nov 29, 2016	Aug 11, 2018	4 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
515	327: Accumulation, Fatty acid	459: Increase, Liver steatosis	Nov 29, 2016	Dec 3, 2016	4 AOPs 58: NR1I3 (CAR) suppression leading to hepatic steatosis 36: Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis 60: NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis 57: AhR activation leading to hepatic steatosis
563	566: impaired, Larval development	563: Death/Failure, Colony	Nov 29, 2016	Dec 3, 2016	4 AOPs 82: Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure 86: Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure 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
583	341: Impairment, Learning and memory	560: Abnormal, Foraging activity and behavior	Nov 29, 2016	Dec 3, 2016	4 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 89: Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure 88: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste
908	177: Increase, Mitochondrial dysfunction	890: Degeneration of dopaminergic neurons of the nigrostriatal pathway	Nov 29, 2016	Oct 3, 2025	4 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
872	425: Thyroidal Iodide, Decreased	277: TH synthesis, Decreased	Nov 29, 2016	Jun 4, 2018	4 AOPs 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 176: Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis 188: Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
11	12: AchE Inhibition	10: ACh Synaptic Accumulation	Nov 29, 2016	Sep 10, 2023	4 AOPs 16: Acetylcholinesterase inhibition leading to acute mortality 281: Acetylcholinesterase Inhibition Leading to Neurodegeneration 312: Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement 405: Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
366	279: Thyroperoxidase, Inhibition	281: T4 in serum, Decreased	Nov 29, 2016	Nov 18, 2025	4 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 175: Thyroperoxidase inhibition leading to altered amphibian metamorphosis 363: Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
208	188: Neuroinflammation	352: N/A, Neurodegeneration	Nov 29, 2016	Feb 23, 2021	4 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. 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 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 471: Neuron defect induced early behavioral change
361	388: Overactivation, NMDARs	389: Increased, Intracellular Calcium overload	Nov 29, 2016	Sep 10, 2023	4 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. 281: Acetylcholinesterase Inhibition Leading to Neurodegeneration 464: Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits 475: Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
363	177: Increase, Mitochondrial dysfunction	55: Cell injury/death	Nov 29, 2016	Nov 29, 2016	4 AOPs 144: Endocytic lysosomal uptake leading to liver fibrosis 48: Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. 530: Endocytotic lysosomal uptake leads to intestinal barrier disruption 624: Increased 11β-Hydroxysteroid dehydrogenase type 1 activity leading to MASLD progression via insulin resistance-associated mitochondrial dysfunction
403	281: T4 in serum, Decreased	402: Cognitive function, decreased	Nov 29, 2016	Apr 27, 2026	4 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 458: AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
2131	1690: Decrease, circulating testosterone levels	1614: Decrease, AR activation	May 11, 2020	Mar 20, 2026	4 AOPs 288: Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) 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 575: Decreased testosterone synthesis leading to increased nipple retention (NR) in male (rodent) offspring
2130	26: Antagonism, Androgen receptor	1614: Decrease, AR activation	May 11, 2020	Mar 20, 2026	4 AOPs 306: Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring 344: Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring 477: Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring 345: Androgen receptor (AR) antagonism leading to decreased fertility in females
2101	1619: Increase, DNMT inhibition	1773: Decrease, Global DNA methylation	Apr 30, 2020	Apr 30, 2020	4 AOPs 336: DNA methyltransferase inhibition leading to population decline (1) 337: DNA methyltransferase inhibition leading to population decline (2) 340: DNA methyltransferase inhibition leading to transgenerational effects (1) 341: DNA methyltransferase inhibition leading to transgenerational effects (2)
1886	328: Decrease, Fecundity	360: Decrease, Population growth rate	Apr 22, 2019	Apr 22, 2019	4 AOPs 336: DNA methyltransferase inhibition leading to population decline (1) 337: DNA methyltransferase inhibition leading to population decline (2) 338: DNA methyltransferase inhibition leading to population decline (3) 444: Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
1880	1617: Inhibition, 5α-reductase	1613: Decrease, DHT level	Apr 18, 2019	Mar 20, 2026	4 AOPs 289: Inhibition of 5α-reductase leading to impaired fecundity in female fish 305: 5α-reductase inhibition leading to short anogenital distance (AGD) 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
1911	1635: Increase, DNA strand breaks	155: Inadequate DNA repair	May 19, 2019	Mar 8, 2024	4 AOPs 296: Oxidative DNA damage leading to chromosomal aberrations and mutations 272: Deposition of energy leading to lung cancer 478: Deposition of energy leading to occurrence of cataracts 644: Bulky DNA adducts leading to chromosomal aberrations and mutations
1935	1613: Decrease, DHT level	1614: Decrease, AR activation	Jun 3, 2019	Mar 20, 2026	4 AOPs 288: Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) 305: 5α-reductase inhibition leading to short anogenital distance (AGD) 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
1912	155: Inadequate DNA repair	1636: Increase, Chromosomal aberrations	May 19, 2019	Dec 17, 2024	4 AOPs 296: Oxidative DNA damage leading to chromosomal aberrations and mutations 272: Deposition of energy leading to lung cancer 478: Deposition of energy leading to occurrence of cataracts 644: Bulky DNA adducts leading to chromosomal aberrations and mutations
3363	1505: Cell cycle disruption	1821: Decrease, Cell proliferation	Oct 8, 2024	Jun 23, 2026	4 AOPs 591: DBDPE-induced DNA damage increase in liver leading to Non-alcoholic fatty liver disease via liver steatosis and inhibition of regeneration 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 324: Reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell cycle disruption
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
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
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

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