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Showing 76 to 100 of 3158 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

3716	2137: Increase, Gonadotropins concentration in plasma	2402: Increased, E2 production in ovaries	Jan 29, 2026	Jun 2, 2026	4 AOPs 623: Activation, estrogen receptor alpha leads to persistent vaginal cornification via increased kisspeptin release 637: Activation, estrogen receptor alpha leads to increased uterine weight via earlier proliferation of cells of the uterine lining 639: Activation, estrogen receptor alpha leads to precocious puberty via increased kisspeptin release 640: Activation, estrogen receptor alpha leads to decreased fertility via prolonged estrus cycle
3717	2402: Increased, E2 production in ovaries	2294: Plasma E2, increased	Jan 29, 2026	Jun 2, 2026	4 AOPs 623: Activation, estrogen receptor alpha leads to persistent vaginal cornification via increased kisspeptin release 637: Activation, estrogen receptor alpha leads to increased uterine weight via earlier proliferation of cells of the uterine lining 639: Activation, estrogen receptor alpha leads to precocious puberty via increased kisspeptin release 640: Activation, estrogen receptor alpha leads to decreased fertility via prolonged estrus cycle
2810	1392: Increase, Oxidative Stress	1634: Increase, Oxidative DNA damage	Dec 16, 2022	Mar 8, 2024	4 AOPs 478: Deposition of energy leading to occurrence of cataracts 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
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
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
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
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
3264	1392: Increase, Oxidative Stress	1097: Occurrence, renal proximal tubular necrosis	Jul 3, 2024	Jul 3, 2024	4 AOPs 138: Organic anion transporter (OAT1) inhibition leading to renal failure and mortality 177: Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality 186: unknown MIE leading to renal failure and mortality 447: Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
2588	1366: Decrease, Oogenesis	78: Reduction, Cumulative fecundity and spawning	Mar 1, 2022	Mar 1, 2022	4 AOPs 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 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
2769	1686: Energy Deposition	1392: Increase, Oxidative Stress	Sep 28, 2022	Aug 26, 2024	4 AOPs 470: Deposition of energy leads to abnormal vascular remodeling 483: Deposition of Energy Leading to Learning and Memory Impairment 482: Deposition of energy leading to occurrence of bone loss 478: Deposition of energy leading to occurrence of cataracts
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
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
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
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
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
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)
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
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
1310	1243: Altered, Ca2+-calmodulin activated signal transduction	341: Impairment, Learning and memory	Nov 29, 2016	Dec 3, 2016	4 AOPs 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 77: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 87: Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
1327	626: Increased, serotonin (5-HT)	1142: Increased, valve movement	Jan 17, 2017	Jan 17, 2017	4 AOPs 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
1430	1317: Decreased, serotonin transporter activity	1320: Increased, extracellular serotonin	Apr 14, 2017	Apr 14, 2017	4 AOPs 214: Network of SSRIs (selective serotonin reuptake inhibitors) 221: Mental stress to depression 222: Mental stress to agitation 226: SSRI (Selective serotonin reuptake inhibitor) to hypertension
1431	1317: Decreased, serotonin transporter activity	1323: Decreased, intracellular serotonin	Apr 14, 2017	Apr 14, 2017	4 AOPs 214: Network of SSRIs (selective serotonin reuptake inhibitors) 221: Mental stress to depression 222: Mental stress to agitation 226: SSRI (Selective serotonin reuptake inhibitor) to hypertension

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