Key Events

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ID	Title	Biological organization	Creation Date	Last Updated	AOPs
2157	Abnormal Cardiac Structure and Function	Organ	Jul 31, 2023	Jul 31, 2023
2264	Lysolecithin cell membrane integration, increased	Cellular	Oct 1, 2024	Oct 1, 2024	Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration
2263	Lysolecithin, increased	Cellular	Oct 1, 2024	Oct 1, 2024	Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
1253	MLL chromosomal translocation	Cellular	Dec 16, 2016	Aug 1, 2022	Inhibitor binding to topoisomerase II leading to infant leukaemia
2262	Neuropathy target esterase, inhibited	Molecular	Oct 1, 2024	Oct 1, 2024	Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
2265	Oligodendrocyte death, increased	Cellular	Oct 1, 2024	Oct 1, 2024	Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
281	Thyroxine (T4) in serum, Decreased	Tissue	Nov 29, 2016	Oct 10, 2022	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to altered amphibian metamorphosis Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse Kidney dysfunction by decreased thyroid hormone Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis Pendrin inhibition leading to altered amphibian metamorphosis Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1094	, hyperuricemia		Nov 29, 2016	Nov 29, 2016
1027	, Learning and memory, impairment		Nov 29, 2016	Nov 29, 2016
1796	11β-hydroxylase inhibition	Molecular	Jul 13, 2020	Jul 13, 2020	Inhibition of 11β-hydroxylase leading to decresed population trajectory
2250	17β-Hydroxysteroid dehydrogenase 2, inhibition	Molecular	Aug 9, 2024	Aug 12, 2024
1387	7α-hydroxypregnenolone synthesis in the brain, decreased	Cellular	May 2, 2017	May 17, 2017	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
382	Aberrant, Dendritic morphology	Cellular	Nov 29, 2016	Sep 16, 2017	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
2208	Aberrant, synaptic formation and plasticity	Organ	Jan 25, 2024	Jan 25, 2024	Estrogen antagonism leading to increased risk of autism-like behavior Binding and activation of GPER leading to learning and memory impairments
2166	Abnormal expression of NO	Cellular	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
1995	Abnormal lipid metabolism	Cellular	Apr 7, 2022	Apr 7, 2022	G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
560	Abnormal, Foraging activity and behavior	Individual	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure Weather event contributes abnormal foraging leading to colony loss/failure Nosema infection increases energetic demands leading to colony loss/failure
1952	Abnormal, Glucose homeostasis	Organ	Nov 18, 2021	Nov 18, 2021	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
183	Abnormal, Morphogenesis		Nov 29, 2016	Nov 29, 2016
2094	Abnormal, neuroblast migration	Cellular	Jan 19, 2023	Jan 19, 2023	Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
1891	abnormal, placental labyrinth vasculature morphology	Tissue	May 31, 2021	May 31, 2021	AhR activation leading to preeclampsia
1108	Abnormal, Role change within caste	Population	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Nosema infection causes abnormal role change that leads to colony loss/failure
564	Abnormal, Roll change within caste	Population	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
535	Abnormal, Sperm penetration (polyspermy)	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
1684	Abnormalities, Cardiac outflow tract formation	Organ	Aug 13, 2019	Aug 13, 2019	TBX1 inhibition leading to congenital cardiac conotruncal anomalies
2242	Abnormality, dendritic spine morphology	Cellular	Jul 14, 2024	Jul 14, 2024	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
1591	Absorption of photon energy	Molecular	Feb 3, 2019	Feb 5, 2019
571	Accelerated, Aging	Individual	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
1605	Accumulation of misfolded proteins	Cellular	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
46	Accumulation, Biological membranes	Cellular	Nov 29, 2016	Sep 16, 2017	Narcosis leading to respiratory failure
68	Accumulation, Collagen	Tissue	Nov 29, 2016	May 17, 2023	Protein Alkylation leading to Liver Fibrosis Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis Endocytic lysosomal uptake leading to liver fibrosis Binding to ACE2 leading to lung fibrosis Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
1942	Accumulation, Cytosolic toxic Tau oligomers	Cellular	Oct 26, 2021	Oct 26, 2021	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
570	Accumulation, Damaged mitochondrial DNA	Cellular	Nov 29, 2016	Sep 16, 2017	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
327	Accumulation, Fatty acid	Organ	Nov 29, 2016	Sep 16, 2017	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis AhR activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
846	Accumulation, Highly carboxylated porphyrins	Organ	Nov 29, 2016	May 7, 2018	Aryl hydrocarbon receptor activation leading to uroporphyria
291	Accumulation, Triglyceride	Cellular	Nov 29, 2016	Mar 26, 2024	LXR activation leading to hepatic steatosis AhR activation leading to hepatic steatosis Glucocorticoid Receptor activation leading to hepatic steatosis Pregnane X Receptor (PXR) activation leads to liver steatosis Liver X Receptor (LXR) activation leads to liver steatosis Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
1938	ACE2 increased shedding	Molecular	Oct 17, 2021	Oct 17, 2021	ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
1876	ACE2 shedding effects on viral entry	Cellular	Apr 28, 2021	Apr 28, 2021
10	Acetylcholine accumulation in synapses	Cellular	Nov 29, 2016	Jun 26, 2020	Acetylcholinesterase inhibition leading to acute mortality Acetylcholinesterase Inhibition Leading to Neurodegeneration Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function Various neuronal effects induced by elavl3, sox10, and mbp
12	Acetylcholinesterase (AchE) Inhibition	Cellular	Nov 29, 2016	Apr 29, 2020	Acetylcholinesterase inhibition leading to acute mortality Acetylcholinesterase Inhibition Leading to Neurodegeneration Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality Various neuronal effects induced by elavl3, sox10, and mbp
1724	Acinar cell proliferation	Cellular	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
1340	Activate, calmodulin	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
1359	Activate, GABA-A receptor	Molecular	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
1379	Activate, leukocyte	Cellular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1380	Activate, mucosal defense	Tissue	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1383	Activate, phospholipase	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation Helicobacter pylori to gastric ulcer
1337	Activate, PLC (Phospholipase C)	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
1360	Activate, presynaptic neuron 2	Molecular	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
2173	Activated AKT/ERK/PI3K pathway	Cellular	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
2170	Activated ANG/Tie2 pathway	Molecular	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
2171	Activated BMP/TGF-beta pathway	Cellular	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
2172	Activated Wnt/Frizzled pathway	Cellular	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
1385	Activated, gastric ulcer formation	Organ	Apr 17, 2017	Jun 2, 2017	Gastric ulcer formation NSAID induced PTGS1 inactivation to gastric ulcer NSAID induced PTGS2 inactivation to gastric ulcer Helicobacter pylori to gastric ulcer
1421	Activated, LXR	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
1355	Activated, membrane depolarization	Cellular	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy presynaptic neuron 2 repression to epilepsy
1351	Activated, NMDA receptor	Molecular	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy
1349	Activated, presynaptic neuron 1	Molecular	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy Various neuronal effects induced by elavl3, sox10, and mbp
1352	Activated, voltage-gated sodium channel	Molecular	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy
2169	Activation of Angiogenic cytokines	Cellular	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
2168	Activation of angiopoietin like protein 4	Cellular	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
2038	Activation of calpain signalling	Cellular	Jul 25, 2022	Jul 25, 2022	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
1448	activation of CCAAT/enhancer-binding protein alpha	Molecular	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
1391	Activation of Cyp2E1	Molecular	May 30, 2017	Jun 19, 2021	Cyp2E1 Activation Leading to Liver Cancer Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality
1815	Activation of ER stress	Cellular	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
1606	Activation of hepatic stellate cells	Cellular	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
2009	Activation of inflammation pathway	Cellular	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
2036	Activation of metabotropic glutamate receptor	Molecular	Jul 25, 2022	Jul 25, 2022	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
2146	Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2	Molecular	May 25, 2023	Jul 28, 2023	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
2167	Activation of MMP-2 MMP-9	Cellular	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
1238	Activation of oxidative stress pathway	Molecular	Nov 29, 2016	Jun 19, 2017
2165	Activation of PPAR	Cellular	Aug 20, 2023	Aug 20, 2023	Demethylation of PPAR promotor leading to vascular disrupting effects
1507	Activation of PPARγ	Molecular	Mar 18, 2018	Mar 18, 2018
2249	Activation of sensory receptors	Molecular	Jul 29, 2024	Jul 29, 2024
1028	Activation of specific nuclear receptors, PPAR-gamma activation	Molecular	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters Epigenetic modification of PPARG leading to adipogenesis
288	Activation of specific nuclear receptors, Transcriptional change	Cellular	Nov 29, 2016	Sep 16, 2017	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
1271	Activation of TGF-β signaling	Cellular	Feb 15, 2017	Feb 15, 2017	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
1974	Activation of Tumor Protein 53	Cellular	Mar 9, 2022	Mar 17, 2022	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
2163	Activation Sema6A	Cellular	Aug 20, 2023	Aug 20, 2023	Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
1288	Activation, 3-hydroxy-3-methylglutaryl-CoA reductase gene	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
1336	Activation, 5-HT2A (Serotonin 2A)	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
9	Activation, 5HT2c	Molecular	Nov 29, 2016	Sep 16, 2017	Kidney toxicity induced by activation of 5HT2C
18	Activation, AhR	Molecular	Nov 29, 2016	Feb 28, 2024	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 AhR activation leading to hepatic steatosis Aryl hydrocarbon receptor activation leading to uroporphyria Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR AhR activation leading to preeclampsia Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway Activation of the AhR leading to metastatic breast cancer Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation leading to liver fibrosis AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1299	Activation, AKT	Molecular	Apr 12, 2017	Apr 12, 2017	G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
484	Activation, AKT2	Molecular	Nov 29, 2016	Sep 16, 2017	AKT2 activation leading to hepatic steatosis
785	Activation, Androgen receptor	Molecular	Nov 29, 2016	Dec 3, 2016	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat) Androgen receptor activation leading to prostate cancer
1309	Activation, aPKC	Molecular	Apr 13, 2017	Apr 13, 2017
1038	Activation, beta-2 adrenergic receptor	Molecular	Nov 29, 2016	Sep 16, 2017	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
1575	Activation, Caspase 8 pathway	Molecular	Jan 7, 2019	Mar 7, 2019	IKK complex inhibition leading to liver injury
2188	Activation, caspases	Cellular	Sep 14, 2023	Sep 14, 2023	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
66	Activation, ChREBP	Molecular	Nov 29, 2016	Sep 16, 2017	LXR activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis
715	Activation, Constitutive androstane receptor	Molecular	Nov 29, 2016	Jun 28, 2018	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
398	Activation, Dendritic Cells	Cellular	Nov 29, 2016	Dec 3, 2020	Covalent Protein binding leading to Skin Sensitisation Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
2164	Activation, Dll4-Notch pathway	Cellular	Aug 20, 2023	Aug 20, 2023	Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
941	Activation, EGFR	Molecular	Nov 29, 2016	Mar 8, 2023	EGFR Activation Leading to Decreased Lung Function
913	Activation, Epidermal Growth Factor Receptor		Nov 29, 2016	Nov 29, 2016
1181	Activation, Estrogen receptor	Molecular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
1065	Activation, estrogen receptor alpha	Molecular	Nov 29, 2016	Aug 14, 2024	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse. Estrogen Receptor Alpha Agonism leads to Impaired Reproduction Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
116	Activation, FAS	Molecular	Nov 29, 2016	Sep 16, 2017	LXR activation leading to hepatic steatosis
1197	Activation, Fibroblasts	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1293	Activation, FOXO	Cellular	Feb 15, 2017	Sep 16, 2017	Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
1304	Activation, FXR	Molecular	Apr 12, 2017	Apr 12, 2017
122	Activation, Glucocorticoid Receptor	Molecular	Nov 29, 2016	Jul 7, 2020	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility Network of SSRIs (selective serotonin reuptake inhibitors) Glucocorticoid Receptor activation leading to hepatic steatosis Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
760	Activation, Glutamate-gated chloride channel	Molecular	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to acute mortality
1018	Activation, Glutamate-gated chloride channels	Molecular	Nov 29, 2016	Sep 16, 2017	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality Various neuronal effects induced by elavl3, sox10, and mbp
1157	Activation, Hepatic nuclear receptor(s)	Molecular	Nov 29, 2016	Sep 16, 2017	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
1280	Activation, HIF-1	Cellular	Feb 15, 2017	Sep 16, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
2162	Activation, HIF1α	Cellular	Aug 20, 2023	Aug 20, 2023	Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
1303	Activation, HSD17B4	Molecular	Apr 12, 2017	Apr 12, 2017
151	Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways	Molecular	Nov 29, 2016	Nov 5, 2020
1297	Activation, insulin receptor	Molecular	Apr 12, 2017	Apr 12, 2017
762	Activation, ionotropic GABA Receptor chloride channel	Molecular	Nov 29, 2016	Sep 16, 2017	Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality
1282	Activation, JAK/STAT pathway	Cellular	Feb 15, 2017	Sep 16, 2017	Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure
1292	Activation, JNK	Cellular	Feb 15, 2017	Sep 16, 2017	Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1205	Activation, Juvenile hormone receptor	Molecular	Nov 29, 2016	Sep 16, 2017	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
826	Activation, Keratinocytes	Cellular	Nov 29, 2016	Sep 16, 2017	Covalent Protein binding leading to Skin Sensitisation
1302	Activation, L-FABP	Molecular	Apr 12, 2017	Apr 13, 2017
1468	Activation, Latent Transforming Growth Factor Beta 1	Molecular	Aug 16, 2017	Aug 16, 2017	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
165	Activation, Long term AHR receptor driven direct and indirect gene expression changes	Cellular	Nov 29, 2016	Dec 2, 2016	Sustained AhR Activation leading to Rodent Liver Tumours
1314	Activation, LRH-1	Molecular	Apr 13, 2017	Apr 13, 2017
167	Activation, LXR	Molecular	Nov 29, 2016	May 21, 2024	LXR activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis Liver X Receptor (LXR) activation leads to liver steatosis
483	Activation, LXR alpha	Molecular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
1198	Activation, Macrophages	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1998	Activation, Microglia	Cellular	Apr 7, 2022	Apr 7, 2022	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
1300	Activation, mTORC1	Molecular	Apr 12, 2017	Apr 12, 2017	G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
1298	Activation, mTORC2	Molecular	Apr 12, 2017	Apr 12, 2017
879	Activation, MTTP	Cellular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
1602	Activation, Muscarinic Acetylcholine Receptors	Molecular	Feb 6, 2019	Apr 17, 2020	Acetylcholinesterase Inhibition Leading to Neurodegeneration
1174	Activation, NADPH Oxidase	Molecular	Nov 29, 2016	Sep 16, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
559	Activation, Nicotinic acetylcholine receptor	Molecular	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure
479	Activation, NR1H4	Molecular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
478	Activation, NRF2	Molecular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
2030	Activation, PARP1	Molecular	Jul 18, 2022	Jul 18, 2022	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
1310	Activation, PI3K	Molecular	Apr 13, 2017	Apr 13, 2017	G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
227	Activation, PPARα	Molecular	Nov 29, 2016	Dec 28, 2020	PPARα activation in utero leading to impaired fertility in males PPARα activation leading to impaired fertility in adult male rodents NFE2L2/FXR activation leading to hepatic steatosis PPARα activation leading to hepatocellular adenomas and carcinomas in rodents PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
234	Activation, PPARα & PPARγ	Molecular	Nov 29, 2016	Dec 3, 2016
380	Activation, Pre-MIE: Metabolism of AFB1	Molecular	Nov 29, 2016	Nov 29, 2016
239	Activation, Pregnane-X receptor, NR1l2	Molecular	Nov 29, 2016	May 22, 2024	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Pregnane X Receptor (PXR) activation leads to liver steatosis
1369	Activation, PTGS-1 (Prostaglandin-endoperoxide synthase 1)	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1370	Activation, PTGS-2 (Prostaglandin-endoperoxide synthase 2)	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
245	Activation, PXR/SXR	Molecular	Nov 29, 2016	Sep 16, 2017	Percellome Toxicogenomics Approach for AOP Building: Case study on Pentachlorophenol NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
258	Activation, SCD-1	Molecular	Nov 29, 2016	Sep 16, 2017	LXR activation leading to hepatic steatosis
480	Activation, SHP	Molecular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
924	Activation, Sp1	Molecular	Nov 29, 2016	Aug 20, 2021
457	Activation, SREBF1	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis AKT2 activation leading to hepatic steatosis
1301	Activation, SREBP-1	Molecular	Apr 12, 2017	Apr 12, 2017
264	Activation, SREBP-1c	Molecular	Nov 29, 2016	Sep 16, 2017	LXR activation leading to hepatic steatosis
265	Activation, Stellate cells	Cellular	Nov 29, 2016	Nov 10, 2019	Protein Alkylation leading to Liver Fibrosis Endocytic lysosomal uptake leading to liver fibrosis AhR activation leading to liver fibrosis
978	Activation, Suppression of NFAT activation and hindrance of nuclear localization	Molecular	Nov 29, 2016	Dec 3, 2016
1283	Activation, TGF-beta pathway	Cellular	Feb 15, 2017	Sep 16, 2017	Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1576	Activation, Tissue resident cells (Kuppfer cells)	Cellular	Jan 7, 2019	Jan 7, 2019	IKK complex inhibition leading to liver injury
1469	Activation, Transforming Growth Factor beta pathway	Molecular	Aug 16, 2017	Aug 16, 2017	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
272	Activation/Proliferation, T-cells	Organ	Nov 29, 2016	Nov 5, 2020	Covalent Protein binding leading to Skin Sensitisation Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
1793	Activator protein 1 activation	Cellular	Jul 9, 2020	Jul 9, 2020	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1679	Acute inhalation toxicity	Individual	Jul 3, 2019	Jul 3, 2019
1955	Acute Myeloid Leukemia	Individual	Dec 3, 2021	Dec 3, 2021	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
1937	ADAM17 expression induction	Cellular	Oct 17, 2021	Oct 17, 2021	ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
2177	Adhesion disfunction	Cellular	Aug 21, 2023	Aug 21, 2023
2025	Affected folate transporter	Cellular	Jul 14, 2022	Jul 14, 2022	Ceramide synthase inhibition leading to neural tube defects
25	Agonism, Androgen receptor	Molecular	Nov 29, 2016	Mar 20, 2017	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Androgen receptor agonism leading to male-biased sex ratio Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
111	Agonism, Estrogen receptor	Molecular	Nov 29, 2016	Jun 24, 2024	Estrogen receptor agonism leading to reproductive dysfunction ER agonism leading to skewed sex ratios due to altered sexual differentiation in males ER agonism leading to reduced survival due to renal failure Estrogen receptor agonism leading to reduced survival and population growth due to renal failure Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
1984	Agonism, Estrogen Receptor alpha	Molecular	Apr 5, 2022	Apr 5, 2022
2201	Agonism, Retinoic acid receptor	Molecular	Jan 14, 2024	Jan 24, 2024	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory Retinoic acid receptor agonism during neurodevelopment leading to microcephaly Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function
1586	Airway epithelial injury	Cellular	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
2086	Airway inflammation	Organ	Jan 9, 2023	Jan 17, 2023	AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
2013	Airway remodeling	Organ	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
1907	Airway Surface Liquid Height, Decreased	Tissue	Jul 19, 2021	Sep 9, 2021	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
97	Alkylation, DNA	Molecular	Nov 29, 2016	Sep 16, 2017	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations Alkylation of DNA leading to cancer 1 Alkylation of DNA leading to cancer 2 Alkylation of DNA leading to reduced sperm count
244	Alkylation, Protein	Molecular	Nov 29, 2016	Sep 16, 2017	Protein Alkylation leading to Liver Fibrosis Renal protein alkylation leading to kidney toxicity
1210	Alteration, Food-web structures	Population	Nov 29, 2016	Dec 3, 2016	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
1060	Alteration, lipid metabolism	Cellular	Nov 29, 2016	Oct 30, 2023	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
310	Alteration, Wnt pathway	Cellular	Nov 29, 2016	Sep 16, 2017	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
854	Alterations, Cellular proliferation / hyperplasia	Tissue	Nov 29, 2016	Sep 16, 2017	Sustained AhR Activation leading to Rodent Liver Tumours Androgen receptor activation leading to prostate cancer
2089	Altered Bone Cell Homeostasis	Cellular	Jan 11, 2023	Aug 23, 2024	Deposition of energy leading to occurrence of bone loss
2204	Altered brain morphology	Organ	Jan 14, 2024	Jan 14, 2024	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory
2245	Altered Cell Differentiation Signaling	Molecular	Jul 24, 2024	Aug 23, 2024	Deposition of energy leading to occurrence of bone loss
1560	Altered differentiation	Cellular	Dec 20, 2018	Mar 17, 2022	Histone deacetylase inhibition leads to neural tube defects
2202	Altered expression of cell cycle genes	Molecular	Jan 14, 2024	Mar 7, 2024	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
2022	Altered function of the brain	Organ	Jul 6, 2022	Jul 6, 2022
1214	Altered gene expression specific to CAR activation, Hepatocytes	Cellular	Nov 29, 2016	Dec 19, 2018	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat
17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway	Molecular	Nov 29, 2016	Aug 19, 2021	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway
1921	Altered gene expression, NF-kB dependent Interleukin-6 pathway	Molecular	Aug 19, 2021	Aug 19, 2021	Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
1917	Altered gene expression, NRF2 dependent antioxidant pathway	Molecular	Aug 17, 2021	Aug 19, 2021	PPARG activation leading to intrahepatic cholestasis Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
1923	Altered gene expression, P53 dependent apoptosis pathway	Molecular	Aug 19, 2021	Aug 19, 2021	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway
1920	Altered gene expression, TGF-β dependent fibrosis pathway	Molecular	Aug 19, 2021	Aug 19, 2021	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway
2221	Altered Liver X receptor activity	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
2005	Altered neurotransmission in development	Cellular	May 16, 2022	Jul 24, 2024	Binding to voltage gate sodium channels during development leads to cognitive impairment
2222	Altered peroxisome proliferator–activated receptor alpha activity	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
21	Altered regulation, Alpha hemoglobin	Cellular	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
2066	Altered Signaling Pathways	Molecular	Sep 28, 2022	Feb 13, 2024
2244	Altered Stress Response Signaling	Molecular	Jul 24, 2024	Aug 26, 2024	Deposition of energy leads to abnormal vascular remodeling Deposition of Energy Leading to Learning and Memory Impairment
698	Altered, Action Potential	Cellular	Nov 29, 2016	Mar 31, 2022	Altered ion channel activity leading impaired heart function
1101	Altered, Amphibian metamorphosis	Organ	Nov 29, 2016	Sep 2, 2020	Thyroperoxidase inhibition leading to altered amphibian metamorphosis Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis Pendrin inhibition leading to altered amphibian metamorphosis Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
1243	Altered, Ca2+-calmodulin activated signal transduction	Cellular	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure
317	Altered, Cardiovascular development/function	Organ	Nov 29, 2016	Sep 16, 2017	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
2115	Altered, cholesterol metabolism	Molecular	Feb 22, 2023	Feb 22, 2023	Unknown MIE altering cholesterol metabolism leading to decreased cognition Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
723	Altered, Chromosome number	Cellular	Nov 29, 2016	May 27, 2019	Chemical binding to tubulin in oocytes leading to aneuploid offspring
536	Altered, Chromosome number (polyploid) zygote	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
1211	Altered, food-web structures	Population	Nov 29, 2016	Dec 3, 2016
534	Altered, Formation of cortical envelope	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
1239	Altered, Gene Expression	Molecular	Nov 29, 2016	Mar 6, 2019	Estrogen receptor activation leading to breast cancer Histone deacetylase inhibition leads to neural tube defects Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory
1930	altered, inner ear development	Organ	Aug 23, 2021	Aug 24, 2021	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
339	Altered, Larval development	Individual	Nov 29, 2016	Dec 3, 2016	Estrogen receptor agonism leading to reproductive dysfunction
752	Altered, Meiotic chromosome dynamics	Cellular	Nov 29, 2016	May 27, 2019	Chemical binding to tubulin in oocytes leading to aneuploid offspring Deposition of ionizing energy leads to population decline via impaired meiosis Deposition of ionising energy leads to population decline via pollen abnormal
2259	Altered, Microbial Bile Acid Metabolism	Molecular	Aug 29, 2024	Aug 29, 2024
186	Altered, Neuroanatomy	Organ	Nov 29, 2016	Sep 16, 2017	XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
192	Altered, Neurophysiology	Organ	Nov 29, 2016	Sep 16, 2017	XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
2067	Altered, Nitric Oxide Levels	Cellular	Sep 28, 2022	Apr 13, 2023	Deposition of energy leads to abnormal vascular remodeling
1640	Altered, Photoreceptor patterning	Cellular	May 22, 2019	Jun 16, 2021	Inhibition of retinaldehyde dehydrogenase leads to population decline Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
1240	Altered, Protein Production	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
363	Altered, Reproductive behaviour	Individual	Nov 29, 2016	Dec 3, 2016	Estrogen receptor agonism leading to reproductive dysfunction
1877	Altered, retinal layer structure	Tissue	May 11, 2021	Jul 8, 2022	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure
1829	Altered, Thyroid hormone-dependent gene expression	Molecular	Dec 9, 2020	Dec 9, 2020	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
286	Altered, Transcription of genes by the androgen receptor	Tissue	Nov 29, 2016	Apr 5, 2024	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals) Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to decreased fertility in females 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring Androgen receptor activation leading to prostate cancer Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
1643	Altered, Visual function	Organ	May 22, 2019	Jul 8, 2022	Inhibition of retinaldehyde dehydrogenase leads to population decline Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
2108	Altered, white brain matter	Tissue	Feb 21, 2023	Feb 21, 2023	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition Unknown MIE altering cholesterol metabolism leading to decreased cognition Increased reactive oxygen species production leading to decreased cognitive function Inhibition of voltage-gated sodium channels leading to decreased cognition Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
1673	Alveolar collapse	Cellular	Jul 3, 2019	Oct 27, 2021	Lung surfactant function inhibition leading to decreased lung function
1674	Alveolar reopening	Tissue	Jul 3, 2019	Jul 3, 2019
1428	Analgesia	Individual	Jun 8, 2017	Jun 8, 2017	Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
1127	Anemia, Impaired oxygen and nutrient delivery to tissue, impaired carbon dioxide and waste product removal		Nov 29, 2016	Nov 29, 2016
2160	Angiogenesis disfunction	Organ	Aug 19, 2023	Aug 19, 2023
2181	Angiogenesis dysfunction	Organ	Aug 28, 2023	Aug 28, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction Demethylation of PPAR promotor leading to vascular disrupting effects Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway
1935	Angiotensin (1-7) levels diminished	Molecular	Oct 15, 2021	Oct 15, 2021	ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
1936	Angiotensin II degradation reduced	Molecular	Oct 17, 2021	Oct 17, 2021	ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
1688	anogenital distance (AGD), decreased	Tissue	Aug 30, 2019	Dec 22, 2022	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1685	Anomalies, Congenital cardiac conotruncal	Individual	Aug 13, 2019	Aug 13, 2019	TBX1 inhibition leading to congenital cardiac conotruncal anomalies
1073	anovulation,		Nov 29, 2016	Nov 29, 2016
26	Antagonism, Androgen receptor	Molecular	Nov 29, 2016	Apr 5, 2024	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to decreased fertility in females Androgen receptor antagonism leading to testicular cancer Androgen receptor (AR) antagonism leading to hypospadias in male offspring Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
112	Antagonism, Estrogen receptor	Molecular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor antagonism leading to reproductive dysfunction DNA damage and mutations leading to Metastatic Breast Cancer Estrogen antagonism leading to increased risk of autism-like behavior
2220	Antagonism, Glucocorticoid hormone receptor	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
638	Antagonism, Histamine Receptor (H2)	Molecular	Nov 29, 2016	Sep 16, 2017	Histamine (H2) receptor antagonism leading to reduced survival
2232	Antagonism, Retinoic acid receptors	Molecular	Jun 6, 2024	Jun 6, 2024	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory
2027	Antagonism, Smoothened receptor	Molecular	Jul 15, 2022	Jul 28, 2022	Antagonism of Smoothened receptor leading to orofacial clefting
1656	Antagonism, Thyroid Receptor	Molecular	Jun 8, 2019	Jan 11, 2021	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
1691	Antagonism,LH receptor	Molecular	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
1432	Anti-depressant Activity	Individual	Jun 23, 2017	Jun 23, 2017	Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
1169	Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin	Molecular	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1148	Anticoagulant rodenticide interferes with gamma-carboxyglutamate formation, Inhibition of protein synthesis in bone		Nov 29, 2016	Nov 29, 2016
1262	Apoptosis	Cellular	Feb 7, 2017	Feb 28, 2024	AOP from chemical insult to cell death NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans Histone deacetylase inhibition leading to testicular atrophy Inhibition of N-linked glycosylation leads to liver injury Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway Activation of the AhR leading to metastatic breast cancer Adverse outcome pathway of PM-induced respiratory toxicity AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity Antagonism of Smoothened receptor leading to orofacial clefting Decrease, GLI1/2 target gene expression leads to orofacial clefting Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis Decrease, cholesterol synthesis leads to orofacial clefting Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation Binding and activation of GPER leading to learning and memory impairments Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
525	Apoptosis of adult Leydig cells, Decreased testosterone by adult Leydig cells	Cellular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
2184	Apoptosis of vascular smooth muscle cells	Cellular	Sep 4, 2023	Sep 4, 2023
1817	Apoptotic cell death	Cellular	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
1443	Atherosclerosis	Individual	Jun 29, 2017	Dec 18, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
2209	autism-like behavior	Individual	Jan 25, 2024	Jan 25, 2024	Estrogen antagonism leading to increased risk of autism-like behavior
1814	benzoquinone imine and acylglucuronide metabolites	Molecular	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
1755	beta-catenin activation	Cellular	Mar 23, 2020	Nov 25, 2022	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
214	Bile accumulation, Pathological condition	Cellular	Nov 29, 2016	Sep 16, 2017	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
857	Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain	Molecular	Nov 29, 2016	Nov 29, 2016
667	Binding at picrotoxin site, iGABAR chloride channel	Molecular	Nov 29, 2016	Apr 29, 2019	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
2218	Binding of (ant)agonist to liver X receptor	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
2219	Binding of (ant)agonist to peroxisome proliferator–activated receptor alpha	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
1851	Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R)	Molecular	Mar 30, 2021	Mar 30, 2021	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Binding to ACE2 leading to lung fibrosis
875	Binding of agonist, Ionotropic glutamate receptors	Molecular	Nov 29, 2016	Sep 16, 2017	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons
387	Binding of agonist, NMDARs	Molecular	Nov 29, 2016	Nov 29, 2016
2217	Binding of antagonist to glucocorticoid hormone receptor	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
2216	Binding of antagonist to thyroid hormone receptor	Molecular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
201	Binding of antagonist, NMDA receptors	Molecular	Nov 29, 2016	Jun 13, 2018	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 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
998	Binding of antagonist, PPAR alpha	Molecular	Nov 29, 2016	Sep 16, 2017	Antagonist binding to PPARα leading to body-weight loss
1199	Binding of FK506 to FKBP12,		Nov 29, 2016	Nov 29, 2016
1200	Binding of FK506 to FKBP12, Formation		Nov 29, 2016	Nov 29, 2016
1653	Binding of inhibitor to mitochondrial complex III	Molecular	Jun 7, 2019	Jun 7, 2019	Mitochondrial complex inhibition leading to liver injury
1654	Binding of inhibitor to mitochondrial complex IV	Molecular	Jun 7, 2019	Jun 7, 2019	Mitochondrial complex inhibition leading to liver injury
1655	Binding of inhibitor to mitochondrial complex V	Molecular	Jun 7, 2019	Jun 7, 2019	Mitochondrial complex inhibition leading to liver injury
888	Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I)	Molecular	Nov 29, 2016	Mar 28, 2018	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome Mitochondrial complex inhibition leading to liver injury
1580	Binding of microtubule stabilizing agents (MSA) to microtubules	Molecular	Jan 29, 2019	Jan 29, 2019	Microtubule interacting drugs lead to peripheral neuropathy
1486	Binding of substrate, endocytic receptor	Molecular	Oct 25, 2017	Oct 25, 2017	Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
1485	Binding of substrate, endocytotic receptor	Molecular	Oct 25, 2017	Oct 25, 2017
1252	Binding to (interferes with) topoisomerase II enzyme	Molecular	Dec 16, 2016	Aug 1, 2022	Inhibitor binding to topoisomerase II leading to infant leukaemia
1739	Binding to ACE2	Molecular	Mar 2, 2020	Aug 30, 2023	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality 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 Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia) Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke) SARS-CoV-2 infection leading to hyperinflammation SARS-CoV-2 infection leading to pyroptosis SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction. ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure. Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
1710	Binding to estrogen receptor (ER)-α in immune cells	Molecular	Dec 29, 2019	Aug 14, 2020	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
1956	Binding to hERG channel	Molecular	Dec 13, 2021	Dec 13, 2021
1353	Binding to voltage-gated sodium channel	Molecular	Apr 14, 2017	Jul 31, 2024	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy Binding to voltage gate sodium channels during development leads to cognitive impairment Inhibition of voltage-gated sodium channels leading to decreased cognition
977	Binding, Binding of calcineurin with FK506-FKBP complexes		Nov 29, 2016	Nov 29, 2016
2109	Binding, extracellular matrix protein laminin	Molecular	Feb 21, 2023	Feb 21, 2023	Binding to the extracellular protein laminin leading to decreased cognitive function
1201	Binding, Immunophilins	Molecular	Nov 29, 2016	Oct 17, 2017
261	Binding, SH-/selen-proteins	Molecular	Nov 29, 2016	Sep 16, 2017
1487	Binding, Thiol/seleno-proteins involved in protection against oxidative stress	Molecular	Nov 9, 2017	Jul 15, 2022	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 Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
1831	Binding, Thyroid binding globulin in serum	Molecular	Dec 9, 2020	Dec 9, 2020	Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
957	Binding, Transthyretin in serum	Molecular	Nov 29, 2016	Sep 16, 2017	Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis
718	Binding, Tubulin	Molecular	Nov 29, 2016	Apr 20, 2021	Chemical binding to tubulin in oocytes leading to aneuploid offspring
301	Binding, VEGF-A		Nov 29, 2016	Nov 29, 2016
1716	Blockade of STAT5 phosphorylation	Cellular	Jan 5, 2020	Feb 15, 2021	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
1529	Blockade, L-Type Calcium Channels	Molecular	Jun 19, 2018	Nov 1, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
1570	Blocking of IL-1R	Molecular	Dec 24, 2018	Jun 1, 2019
1874	blood brain barrier disruption	Cellular	Apr 27, 2021	Apr 27, 2021	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
1676	Blood extravasation into the lungs	Organ	Jul 3, 2019	Jul 3, 2019
1132	Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal	Cellular	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1867	Bradykinin system, hyperactivated	Molecular	Apr 20, 2021	Jan 24, 2022	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
2093	Brain thyroid hormone (T4/T3) decreased	Organ	Jan 19, 2023	Jan 19, 2023	Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
1588	Bronchiolitis obliterans	Individual	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans
1879	Bulky DNA adducts, increase	Molecular	May 17, 2021	May 17, 2021	Bulky DNA adducts leading to mutations
1149	Calcium cannot bind to the hydroxyapatite matrix of bone, Osteocalcin and other bone proteins (periostin, MGP and periostin like factor) not formed		Nov 29, 2016	Nov 29, 2016
2001	Cardiac hypertrophy	Organ	Apr 22, 2022	Apr 22, 2022
2190	Cardiomyocyte differentiation inhibition	Cellular	Sep 16, 2023	Sep 16, 2023
2257	Celiac disease	Individual	Aug 13, 2024	Aug 13, 2024	Gluten intake leading to celiac disease - under development
1505	Cell cycle, disrupted	Cellular	Jan 21, 2018	Jun 30, 2021	Histone deacetylase inhibition leading to testicular atrophy AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation Deposition of ionizing energy leads to population decline via impaired meiosis
2103	Cellular dysfunction (human placenta trophoblast cells)	Cellular	Feb 7, 2023	Feb 7, 2023
429	Cellular Proliferation and Clonal Expansion of Mutant Cells (Pre-neoplastic Foci), Alteration of cellular growth homeostasis		Nov 29, 2016	Nov 29, 2016
2228	Cerebellar gene expression. Altered	Molecular	Jun 6, 2024	Jun 6, 2024	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function
2230	Cerebellar hypoplasia	Tissue	Jun 6, 2024	Jun 6, 2024	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function
2229	Cerebellar neuronal differentiation. Decreased	Organ	Jun 6, 2024	Jun 6, 2024	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function
1875	Cerebrovascular disease (stroke)	Organ	Apr 27, 2021	Mar 30, 2022	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke)
853	Changes/Inhibition, Cellular Homeostasis and Apoptosis	Cellular	Nov 29, 2016	Sep 16, 2017	Sustained AhR Activation leading to Rodent Liver Tumours
1564	Chemical induced Fanconi syndrome	Individual	Dec 20, 2018	Dec 20, 2018	Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
357	Cholestasis, Pathology	Individual	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
1454	chronic high fat diet	Individual	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
1603	Chronic kidney disease	Organ	Feb 18, 2019	Feb 18, 2019	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
1894	chronic low grade systemic inflammation	Individual	Jun 24, 2021	Jun 24, 2021
2008	Chronic obstructive pulmonary disease	Individual	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
1753	Chronic reactive oxygen species	Molecular	Mar 23, 2020	Nov 9, 2021	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
1251	Chronic, Mucus hypersecretion	Tissue	Nov 29, 2016	Aug 25, 2021
1908	Cilia Beat Frequency, Decreased	Cellular	Jul 19, 2021	Sep 10, 2021	Oxidative stress Leading to Decreased Lung Function Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
491	Clonal Expansion/Cell Proliferation, to form Altered Hepatic Foci (AHF)	Organ	Nov 29, 2016	Sep 16, 2017	AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
1845	Coagulation	Organ	Mar 25, 2021	Aug 30, 2023	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
402	Cognitive function, decreased	Individual	Nov 29, 2016	Jul 25, 2024	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition Binding to the extracellular protein laminin leading to decreased cognitive function Unknown MIE altering cholesterol metabolism leading to decreased cognition Increased reactive oxygen species production leading to decreased cognitive function Inhibition of voltage-gated sodium channels leading to decreased cognition AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals Binding to voltage gate sodium channels during development leads to cognitive impairment
2075	Cognitive, sensed as hypoxic/low oxygen environment	Organ	Nov 16, 2022	Nov 16, 2022	Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
1275	Collagen Deposition	Tissue	Feb 15, 2017	Feb 15, 2017	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis
1558	Collagen production, reduced	Tissue	Dec 20, 2018	Dec 20, 2018	Histone deacetylase inhibition leads to impeded craniofacial development
1997	Colon epithelial injury	Organ	Apr 7, 2022	Apr 7, 2022
2101	Conformational changes of thyroid receptor	Molecular	Feb 7, 2023	Feb 7, 2023
2131	Conjugation, GSH	Cellular	Apr 5, 2023	Sep 14, 2023	Glutathione conjugation leading to reproductive dysfunction via oxidative stress
1832	Coordinated gene expression changes by PPARα activation	Molecular	Dec 19, 2020	Dec 19, 2020
1835	Cortisol and 11β-(OH) testosterone decreased	Cellular	Feb 9, 2021	Feb 9, 2021	Inhibition of 11β-hydroxylase leading to decresed population trajectory
1221	Cough, Dyspnea, Sneezing, Acute respiratory effect		Nov 29, 2016	Nov 29, 2016
396	Covalent Binding, Protein	Molecular	Nov 29, 2016	Nov 5, 2020	Covalent Protein binding leading to Skin Sensitisation Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
1508	CYP2E1 Activation	Molecular	Mar 26, 2018	Apr 9, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
1386	CYP7B activity, inhibition	Molecular	May 2, 2017	May 17, 2017	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
1906	Cystic Fibrosis Transmembrane Regulator Function, Decreased	Molecular	Jul 19, 2021	Aug 3, 2021	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction
2102	Cytotoxicity (human trophoblast cells)	Cellular	Feb 7, 2023	Feb 7, 2023
829	Damage, Lipid bilayer	Cellular	Nov 29, 2016	Dec 3, 2016	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
250	Damaging, Red blood cells; hemolysis	Cellular	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
563	Death/Failure, Colony	Population	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure Suppression of immune system contributes to impaired development and leads to colony loss/failure Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure Varroa mite infestation increases virus levels leading to colony loss/failure Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure Weather event contributes to colony loss/failure Weather event contributes abnormal foraging leading to colony loss/failure Nosema infection increases energetic demands leading to colony loss/failure Nosema infection causes abnormal role change that leads to colony loss/failure Queen egg-laying decrease leads to colony loss/failure
2200	decline, neural progenitor cells	Organ	Jan 10, 2024	Jan 10, 2024	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
361	Decline, Population	Population	Nov 29, 2016	Dec 3, 2016	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
679	Decline, Population trajectory	Population	Nov 29, 2016	Dec 3, 2016	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
1258	Decompartmentalization	Cellular	Feb 7, 2017	Sep 16, 2017	AOP from chemical insult to cell death
1890	Decrease (loss of) fetal male germ cells	Cellular	May 29, 2021	Nov 11, 2021	Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
1545	Decrease in mitochondrial oxidative phosphorylation	Cellular	Dec 19, 2018	Dec 19, 2018	Mitochondrial complex inhibition leading to liver injury
2215	Decrease Left Ventricular function	Organ	Apr 3, 2024	Apr 3, 2024	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
1696	Decrease of egg production and cummulative fecundity	Individual	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction Deposition of ionizing energy leads to population decline via impaired meiosis
851	Decrease of GABAergic interneurons	Cellular	Nov 29, 2016	Apr 4, 2019	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory
386	Decrease of neuronal network function	Organ	Nov 29, 2016	May 28, 2018	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment 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 Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Excessive iron accumulation leading to neurological disorders Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons Estrogen antagonism leading to increased risk of autism-like behavior Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory
385	Decrease of synaptogenesis	Cellular	Nov 29, 2016	Sep 16, 2017	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory
425	Decrease of Thyroidal iodide	Cellular	Nov 29, 2016	Apr 4, 2019	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
2057	Decrease, hatching of egg	Individual	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2058	Decrease, 20-hydroxyecdysone	Molecular	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
993	Decrease, Abdominal muscle contraction	Tissue	Nov 29, 2016	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
1834	Decrease, Acyl-CoA dehydrogenases	Molecular	Jan 15, 2021	Jan 15, 2021	Glucocorticoid Receptor activation leading to hepatic steatosis
1771	Decrease, Adenosine triphosphate pool	Cellular	Apr 30, 2020	Jun 14, 2021	Excessive reactive oxygen species production leading to mortality (2) Excessive reactive oxygen species production leading to mortality (3) Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation Thermal stress leading to population decline (1) Mitochondrial ATP synthase antagonism leading to growth inhibition (1) Mitochondrial ATP synthase antagonism leading to growth inhibition (2) Mitochondrial complex III antagonism leading to growth inhibition (1) Mitochondrial complex III antagonism leading to growth inhibition (2) Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
1614	Decrease, androgen receptor activation	Tissue	Apr 10, 2019	Apr 5, 2024	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring Androgen receptor antagonism leading to testicular cancer Androgen receptor (AR) antagonism leading to hypospadias in male offspring Androgen receptor (AR) antagonism leading to decreased fertility in females
914	Decrease, Apoptosis of ciliated epithelial cells	Cellular	Nov 29, 2016	Aug 17, 2021
35	Decrease, Aromatase (Cyp19a1)	Cellular	Nov 29, 2016	Nov 29, 2016
1966	Decrease, Asexual reproduction	Individual	Jan 17, 2022	Jan 17, 2022
1472	Decrease, ATP production	Cellular	Oct 10, 2017	Apr 11, 2021	Reduction in photophosphorylation leading to growth inhibition in aquatic plants Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
1808	Decrease, ATP synthase activity	Molecular	Nov 2, 2020	Nov 2, 2020
1534	Decrease, Blood pressure	Individual	Jun 19, 2018	Jun 19, 2018
1531	Decrease, Calcium binding to Troponin C	Cellular	Jun 19, 2018	Jun 19, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
1530	Decrease, Calcium currents	Cellular	Jun 19, 2018	Jun 19, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
1532	Decrease, Cardiac contractility	Organ	Jun 19, 2018	Jun 19, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
1533	Decrease, Cardiac ejection fraction	Organ	Jun 19, 2018	Jun 19, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
1821	Decrease, Cell proliferation	Cellular	Nov 12, 2020	Dec 7, 2020	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation Mitochondrial ATP synthase antagonism leading to growth inhibition (1) Mitochondrial complex III antagonism leading to growth inhibition (1) Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) Antagonism of Smoothened receptor leading to orofacial clefting Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion Decrease, GLI1/2 target gene expression leads to orofacial clefting Decrease, cholesterol synthesis leads to orofacial clefting
2060	Decrease, Chitin laminar organization	Tissue	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
1473	Decrease, Chlorophyll synthesis	Cellular	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
1266	Decrease, Circulating crustacean cardioactive peptide	Tissue	Feb 9, 2017	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
988	Decrease, Circulating ecdysis triggering hormone	Tissue	Nov 29, 2016	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
1446	Decrease, Coupling of oxidative phosphorylation	Molecular	Jun 29, 2017	May 28, 2021	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
1523	Decrease, Cuticular chitin content	Tissue	May 24, 2018	Feb 17, 2021	S-adenosylmethionine depletion leading to population decline (2) S-adenosylmethionine depletion leading to population decline (1) Chitin synthase 1 inhibition leading to mortality Sulfonylureareceptor binding leading to mortality
1313	Decrease, cytosolic fatty acid	Molecular	Apr 13, 2017	Apr 13, 2017
996	Decrease, Digestion of old cuticle	Organ	Nov 29, 2016	Oct 21, 2020	Chitinase inhibition leading to mortality Chitobiase inhibition leading to mortality
1613	Decrease, dihydrotestosterone (DHT) level	Tissue	Apr 10, 2019	Apr 5, 2024	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) Inhibition of 5α-reductase leading to impaired fecundity in female fish 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
2052	Decrease, dopa decarboxylase	Cellular	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
1056	Decrease, E2 blood concentrations at hypothalamus	Tissue	Nov 29, 2016	Sep 16, 2017	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
1267	Decrease, Ecdysis motoneuron bursts	Tissue	Feb 9, 2017	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
2196	Decrease, elavl3	Molecular	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
1268	Decrease, Excitatory postsynaptic potential	Tissue	Feb 9, 2017	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
1699	Decrease, expression of gonadotropin releasing hormone receptor	Molecular	Oct 30, 2019	Oct 30, 2019	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
1824	Decrease, Fatty acid β-oxidation	Cellular	Nov 25, 2020	Nov 25, 2020
328	Decrease, Fecundity	Individual	Nov 29, 2016	Jun 12, 2018	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (3) DNA methyltransferase inhibition leading to population decline (4) Thermal stress leading to population decline (3) Thermal stress leading to population decline (2) Thermal stress leading to population decline (1) Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
1781	Decrease, Fecundity (F3)	Individual	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2)
330	Decrease, Fertility	Individual	Nov 29, 2016	Jun 29, 2017	HMG-CoA reductase inhibition leading to decreased fertility
2040	Decrease, GLI1/2 target gene expression	Cellular	Jul 25, 2022	Mar 22, 2023	Antagonism of Smoothened receptor leading to orofacial clefting Decrease, GLI1/2 target gene expression leads to orofacial clefting Decrease, cholesterol synthesis leads to orofacial clefting
2028	Decrease, GLI1/2 translocation to nucleus	Molecular	Jul 15, 2022	Oct 28, 2022	Antagonism of Smoothened receptor leading to orofacial clefting Decrease, cholesterol synthesis leads to orofacial clefting
1773	Decrease, Global DNA methylation	Molecular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2)
2071	Decrease, Glucose pool	Cellular	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
1951	Decrease, Glucose uptake	Cellular	Nov 18, 2021	Nov 18, 2021	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
1949	Decrease, GLUT4	Cellular	Nov 18, 2021	Nov 18, 2021	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
1476	Decrease, Glycolysis	Cellular	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
1521	Decrease, Growth	Individual	May 24, 2018	Jul 6, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation Mitochondrial ATP synthase antagonism leading to growth inhibition (1) Mitochondrial ATP synthase antagonism leading to growth inhibition (2) Mitochondrial complex III antagonism leading to growth inhibition (1) Mitochondrial complex III antagonism leading to growth inhibition (2) Reduction in photophosphorylation leading to growth inhibition in aquatic plants Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
1778	Decrease, Heritable DNA methylation (F3)	Molecular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2)
633	Decrease, histaminergic neuron excitation	Cellular	Nov 29, 2016	Sep 16, 2017	Histamine (H2) receptor antagonism leading to reduced survival
788	Decrease, Incorporation of active iodide into iodotyrosines	Cellular	Nov 29, 2016	Sep 16, 2017
867	Decrease, Intracellular pH	Cellular	Nov 29, 2016	Sep 16, 2017	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
2059	Decrease, knickkopf gene	Cellular	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
1478	Decrease, Leaf cell mitosis	Tissue	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
1479	Decrease, Leaf development	Organ	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
1377	Decrease, leukocyte adherence	Tissue	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1474	Decrease, Light harvest capacity	Cellular	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
1250	Decrease, Lung function	Individual	Nov 29, 2016	Sep 8, 2021	EGFR Activation Leading to Decreased Lung Function Lung surfactant function inhibition leading to decreased lung function Oxidative stress Leading to Decreased Lung Function Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
2198	Decrease, mbp	Molecular	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
40	Decrease, Mitochondrial ATP production	Cellular	Nov 29, 2016	Sep 16, 2017	Calcium-mediated neuronal ROS production and energy imbalance Reduction in photophosphorylation leading to growth inhibition in aquatic plants Renal protein alkylation leading to kidney toxicity Deposition of ionising energy leading to population decline via mitochondrial dysfunction Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
1770	Decrease, Mitochondrial membrane potential	Cellular	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (2) Deposition of ionising energy leading to population decline via mitochondrial dysfunction Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
2063	Decrease, New cuticle secretion	Organ	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
572	Decrease, Number of worker bees	Population	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure Suppression of immune system contributes to impaired development and leads to colony loss/failure Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
1366	Decrease, Oogenesis	Organ	Apr 15, 2017	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (3) DNA methyltransferase inhibition leading to population decline (4) Thermal stress leading to population decline (3) Thermal stress leading to population decline (2) Thermal stress leading to population decline (1) Deposition of energy leading to population decline via DNA strand breaks and follicular atresia Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and follicular atresia Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Deposition of ionizing energy leads to population decline via impaired meiosis
1782	Decrease, Oogenesis (F3)	Organ	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2)
488	Decrease, Ovulation	Organ	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction
1477	Decrease, Oxidative phosphorylation	Cellular	Oct 10, 2017	Dec 20, 2018	Reduction in photophosphorylation leading to growth inhibition in aquatic plants Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome Excessive reactive oxygen species production leading to mortality (2) Deposition of ionising energy leading to population decline via mitochondrial dysfunction
2041	Decrease, palatal shelf outgrowth	Tissue	Jul 27, 2022	May 16, 2023	Antagonism of Smoothened receptor leading to orofacial clefting Decrease, GLI1/2 target gene expression leads to orofacial clefting Decrease, cholesterol synthesis leads to orofacial clefting
1475	Decrease, Photosynthesis	Cellular	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
1517	Decrease, Photosystem II activity	Molecular	May 24, 2018	Oct 7, 2020
1862	Decrease, Photosystem II efficiency	Cellular	Apr 11, 2021	Apr 11, 2021	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
1810	Decrease, Plasma membrane ATPase activity	Cellular	Nov 2, 2020	Nov 2, 2020
360	Decrease, Population growth rate	Population	Nov 29, 2016	Jan 3, 2023	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Aromatase inhibition leading to reproductive dysfunction Estrogen receptor agonism leading to reproductive dysfunction Estrogen receptor antagonism leading to reproductive dysfunction Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint Inhibition of tyrosinase leads to decreased population in fish Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Acetylcholinesterase inhibition leading to acute mortality Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (3) DNA methyltransferase inhibition leading to population decline (4) DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2) Inhibition of 5α-reductase leading to impaired fecundity in female fish Inhibition of retinaldehyde dehydrogenase leads to population decline Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation Thermal stress leading to population decline (3) Thermal stress leading to population decline (2) Thermal stress leading to population decline (1) Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Inhibition of 11β-hydroxylase leading to decresed population trajectory Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory Androgen receptor agonism leading to male-biased sex ratio Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Deposition of ionising energy leading to population decline via mitochondrial dysfunction Deposition of ionising energy leading to population decline via programmed cell death Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) GSK3beta inactivation leading to increased mortality via defects in developing inner ear Deposition of energy leading to population decline via DNA strand breaks and follicular atresia Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and follicular atresia Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone Estrogen receptor agonism leading to reduced survival and population growth due to renal failure Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
2061	Decrease, Prevent chitin degradation by chitinases	Tissue	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
1863	Decrease, Reproduction	Individual	Apr 11, 2021	Apr 11, 2021	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Deposition of ionising energy leading to population decline via mitochondrial dysfunction Deposition of ionising energy leading to population decline via programmed cell death Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis Deposition of ionizing energy leads to population decline via impaired meiosis Deposition of ionising energy leads to population decline via pollen abnormal Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
771	Decrease, Serum thyroid hormone (T4/T3)	Tissue	Nov 29, 2016	Sep 16, 2017	Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
2044	Decrease, Smoothend relocation and activation	Cellular	Aug 23, 2022	Oct 27, 2022	Antagonism of Smoothened receptor leading to orofacial clefting
2043	Decrease, Sonic Hedgehog second messenger production	Cellular	Aug 12, 2022	Mar 22, 2023	Antagonism of Smoothened receptor leading to orofacial clefting Decrease, GLI1/2 target gene expression leads to orofacial clefting Decrease, cholesterol synthesis leads to orofacial clefting
2197	Decrease, sox10	Molecular	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
2020	Decrease, sox9 expression	Molecular	Jun 28, 2022	Sep 25, 2024	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
266	Decrease, Steroidogenic acute regulatory protein (STAR)	Cellular	Nov 29, 2016	Sep 16, 2017	PPARα activation in utero leading to impaired fertility in males
1382	Decrease, surfactant	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation Helicobacter pylori to gastric ulcer
1690	Decrease, testosterone levels	Tissue	Aug 30, 2019	May 24, 2024	Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis HMG-CoA reductase inhibition leading to decreased fertility PPARα activation in utero leading to impaired fertility in males PPARα activation leading to impaired fertility in adult male rodents Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility Inhibition of 5α-reductase leading to Leydig cell tumors (in rat) Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
1687	decrease, transcription of genes by AR	Cellular	Aug 30, 2019	Aug 30, 2019	Androgen receptor antagonism leading to testicular cancer
1622	Decrease, Transgenerational DNA methylation	Molecular	Apr 22, 2019	Apr 22, 2019
289	Decrease, Translocator protein (TSPO)	Cellular	Nov 29, 2016	Sep 16, 2017	PPARα activation in utero leading to impaired fertility in males
1772	Decrease, Triglyceride	Cellular	Apr 30, 2020	May 27, 2024	Excessive reactive oxygen species production leading to mortality (3)
2051	Decrease, Tyrosine	Molecular	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
642	Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol	Molecular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
646	Decreased Cholesterol, Decreased sperm quantity and/or quality in the adult testis	Organ	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
645	Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells	Cellular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
644	Decreased Cholesterol, Decreased Transport of Cholesterol to the Inner Mitochondrial Membrane	Molecular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
643	Decreased Cholesterol, Decreased Uptake of Lipoproteins	Molecular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell
1452	decreased DNA methylation of tyrosine hydroxylase	Cellular	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
1450	decreased dopamine	Molecular	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
2176	Decreased endothelial cell proliferation	Cellular	Aug 21, 2023	Aug 21, 2023
543	Decreased fertility in the adult, Decreased sperm quantity and/or quality in the adult testis	Individual	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
972	Decreased fertility, Reduced number of oocytes ovulated	Individual	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
2026	decreased folate uptake	Cellular	Jul 14, 2022	Jul 14, 2022	Ceramide synthase inhibition leading to neural tube defects
969	Decreased GnRH Release, Decreased Kisspeptin stimulation of GnRH neurons	Cellular	Nov 29, 2016	Sep 16, 2017	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
1571	Decreased IL-1 production	Cellular	Dec 24, 2018	Jun 24, 2019
968	Decreased Kisspeptin release from neurons in AVPV, Decreased hypothalamic estrogen reduces kisspeptinergic neuron response	Cellular	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
970	Decreased LH release from Anterior Pituitary, Decreased GnRH stimulation of Anterior Pituitary Gonadotrophs	Cellular	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
1453	decreased methylation of dopamine transporter promoter	Cellular	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
1751	Decreased mortality	Individual	Mar 17, 2020	Mar 17, 2020
1562	Decreased Na/K ATPase activity	Cellular	Dec 20, 2018	Sep 24, 2024	Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity Na+ /K+ -ATPase inhibition leading to hypertension Decreased Sodium/Potassium ATPase activity leads to Heart failure
1837	decreased oocyte maturation	Organ	Feb 9, 2021	Feb 9, 2021	Inhibition of 11β-hydroxylase leading to decresed population trajectory
1836	Decreased plasma Cortisol level	Tissue	Feb 9, 2021	Feb 9, 2021	Inhibition of 11β-hydroxylase leading to decresed population trajectory
1642	Decreased plasma RA level	Tissue	May 22, 2019	May 22, 2019	Inhibition of retinaldehyde dehydrogenase leads to population decline
967	Decreased positive estrogenic feedback on hypothalamus, Reduced estradiol in circulation decreases estrogen concentration at hypothalamus	Organ	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
2203	Decreased proliferation of cortical neural progenitor cells	Cellular	Jan 14, 2024	Jan 29, 2024	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
1538	Decreased protection against oxidative stress	Cellular	Sep 13, 2018	Jul 15, 2022	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 Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
1563	Decreased proximal tubular vectorial transport	Tissue	Dec 20, 2018	Dec 20, 2018	Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome
1641	Decreased retinoic acid (RA) synthesis	Cellular	May 22, 2019	May 22, 2019	Inhibition of retinaldehyde dehydrogenase leads to population decline
1451	decreased reward	Individual	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
1981	Decreased SIRT1 expression	Cellular	Mar 22, 2022	Mar 24, 2022	DNA damage and mutations leading to Metastatic Breast Cancer
2140	Decreased spawning and cumulative fecundity, decreased gonadosomatic index	Individual	May 16, 2023	May 16, 2023
505	Decreased sperm quantity / quality in the adult, Decreased fertility	Individual	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
520	Decreased sperm quantity or quality in the adult, Decreased fertility	Individual	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1798	Decreased spermatogenesis	Organ	Jul 13, 2020	Feb 9, 2021	Inhibition of 11β-hydroxylase leading to decresed population trajectory Deposition of ionizing energy leads to population decline via impaired meiosis Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability
649	Decreased steroidogenesis, Alterations in the Leydig Cell Cytoskeleton	Tissue	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
648	Decreased steroidogenesis, Increased Apoptosis of Adult Leydig Cells	Tissue	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
640	Decreased steroidogenesis, Proteomic alterations in the adult Leydig cell	Molecular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell
660	decreased testosterone by fetal Leydig cells, Dysgenesis of fetal Leydig cells	Organ	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
659	Decreased testosterone by the fetal Leydig cells, Activation by other estradiol agonists	Cellular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
654	Decreased testosterone by the fetal Leydig cells, Activation by other glucocorticoid receptor agonists	Cellular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
661	Decreased testosterone by the fetal Leydig cells, Alterations in the fetal testis proteome	Molecular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
541	Decreased testosterone by the fetal Leydig cells, Decreased COUP-TFII stem Leydig cells	Cellular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
657	Decreased testosterone by the fetal Leydig cells, Dysgenesis of fetal Leydig cells	Organ	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome
540	Decreased testosterone by the fetal Leydig cells, Dysgensis of fetal Leydig cells	Organ	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
662	Decreased testosterone by the fetal Leydig cells, Hypermethylation in the fetal testis	Molecular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
653	Decreased testosterone by the fetal Leydig cells, Increased corticosterone	Cellular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis
655	Decreased testosterone by the fetal Leydig cells, Increased COUP-TFII in fetal Leydig cells	Cellular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis
658	Decreased testosterone by the fetal Leydig cells, Increased estradiol	Cellular	Nov 29, 2016	Sep 16, 2017	Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis
1756	Decreased, plasma 11-ketotestosterone level	Tissue	Mar 23, 2020	May 24, 2022	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone Inhibition of 11β-hydroxylase leading to decresed population trajectory Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
8	Decreased, 3-hydroxyacyl-CoA dehydrogenase type-2 activity	Cellular	Nov 29, 2016	Sep 16, 2017	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
1401	Decreased, 5-HT3	Tissue	Jun 1, 2017	Jun 1, 2017	Serotonin transporter activation to seizure
1881	Decreased, all-trans retinoic acid (atRA) concentration	Tissue	May 24, 2021	Feb 13, 2023	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
1987	Decreased, Androgen and Progestin	Cellular	Apr 5, 2022	Jun 6, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
742	Decreased, Androgen receptor activity	Molecular	Nov 29, 2016	Dec 3, 2016	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
1409	Decreased, angiogenesis	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS2 inactivation to gastric ulcer
627	Decreased, anxiety	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
1183	Decreased, Apoptosis (Epithelial Cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer Androgen receptor activation leading to prostate cancer
800	Decreased, Aromatase (Cyp19a1) mRNA	Cellular	Nov 29, 2016	Sep 16, 2017	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
2123	decreased, Bcl-2 expression	Molecular	Apr 4, 2023	Sep 7, 2023	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
1407	Decreased, bicarbonate	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
1058	Decreased, bile flow	Organ	Nov 29, 2016	Sep 16, 2017	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
848	Decreased, Binding of NE to NE receptors on GnRH neurons	Cellular	Nov 29, 2016	Sep 16, 2017	Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
2261	Decreased, blood plasma volume	Tissue	Sep 20, 2024	Sep 26, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
315	Decreased, Body length		Nov 29, 2016	Nov 29, 2016
864	Decreased, Body Weight	Individual	Nov 29, 2016	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
52	Decreased, Calcium influx	Cellular	Nov 29, 2016	Jun 13, 2018	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities 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
656	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII)	Cellular	Nov 29, 2016	Jun 6, 2024	Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
1178	Decreased, Chloride conductance		Nov 29, 2016	Nov 29, 2016
807	Decreased, cholesterol	Tissue	Nov 29, 2016	May 24, 2022	HMG-CoA reductase inhibition leading to decreased fertility PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone
533	Decreased, Cortical granule release/distribution upon fertilization	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
527	Decreased, Decreased fecundity	Individual	Nov 29, 2016	Dec 3, 2016	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
482	Decreased, DHB4/HSD17B4	Molecular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
1083	Decreased, Dopaminergic activity	Cellular	Nov 29, 2016	Dec 3, 2016	Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
2233	Decreased, ERαβ heterodimers	Molecular	Jun 19, 2024	Jun 19, 2024	Binding and activation of GPER leading to learning and memory impairments
1319	Decreased, extracellular chloride (Cl-)	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
1347	Decreased, extracellular serotonin	Molecular	Apr 14, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation Serotonin transporter activation to seizure Serotonin transporter activation to depression Serotonin transporter activation to agitation SSRI (Selective serotonin reuptake inhibitor) to hypertension
1318	Decreased, extracellular sodium (Na+)	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
1878	Decreased, Eye size	Organ	May 11, 2021	Jun 24, 2021	Thyroperoxidase inhibition leading to altered visual function via decreased eye size Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
1414	Decreased, GABA	Cellular	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
1179	Decreased, GABA release	Cellular	Nov 29, 2016	Dec 3, 2016	Sodium channel (Nav1.1) inhibition leading to population decline
1145	Decreased, gametogenesis		Nov 29, 2016	Nov 29, 2016
819	Decreased, Glomerular filtration	Tissue	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
578	Decreased, Glucose oxidase enzyme activity	Molecular	Nov 29, 2016	Sep 16, 2017	Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
529	Decreased, GnRH cfos activity	Molecular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
530	Decreased, GnRH pulsatility/release	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
1071	Decreased, GnRH pulsatility/release in hypothalamus	Cellular	Nov 29, 2016	Sep 16, 2017	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
1986	Decreased, Gonadotropins	Molecular	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
140	Decreased, HSD17B10 expression	Cellular	Nov 29, 2016	Sep 16, 2017	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
579	Decreased, Hydrogen peroxide production	Molecular	Nov 29, 2016	Sep 16, 2017	Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
2214	Decreased, Insulin-like peptide 3 (INSL3)	Molecular	Mar 19, 2024	Jul 18, 2024	Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
2121	decreased, Intellectual Quotient	Population	Apr 4, 2023	Apr 4, 2023	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
1416	Decreased, intracellular chloride	Cellular	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
1323	Decreased, intracellular serotonin	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation SSRI (Selective serotonin reuptake inhibitor) to hypertension
1177	Decreased, Ionotropic GABA receptor chloride channel conductance	Cellular	Nov 29, 2016	Dec 3, 2016	Various neuronal effects induced by elavl3, sox10, and mbp
477	Decreased, Ketogenesis	Cellular	Nov 29, 2016	Sep 16, 2017	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
861	Decreased, Ketogenesis (production of ketone bodies)	Cellular	Nov 29, 2016	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
531	Decreased, LH Surge	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation Reduced availability of GnRH leading to uterine adenocarcinoma via increased estrogen availability at target organ level
1072	Decreased, LH Surge from anterior pituitary	Cellular	Nov 29, 2016	Dec 3, 2016	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
635	Decreased, locomotion	Individual	Nov 29, 2016	Dec 3, 2016	Histamine (H2) receptor antagonism leading to reduced survival
166	Decreased, Long-term potentiation (LTP)	Organ	Nov 29, 2016	Sep 16, 2017	Calcium-mediated neuronal ROS production and energy imbalance
168	Decreased, Lymphocytes	Individual	Nov 29, 2016	Dec 3, 2016	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
1988	Decreased, Maturation Inducing Steroid Surge by Granulosa cells	Tissue	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
805	Decreased, mevalonate	Cellular	Nov 29, 2016	Dec 3, 2016	HMG-CoA reductase inhibition leading to decreased fertility
860	Decreased, Mitochondrial Fatty Acid Beta Oxidation	Molecular	Nov 29, 2016	Sep 16, 2017	Glucocorticoid Receptor activation leading to hepatic steatosis
179	Decreased, Mitochondrial fatty acid beta-oxidation	Molecular	Nov 29, 2016	Sep 16, 2017	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
1404	Decreased, mucosal blood flow	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
1406	Decreased, mucous	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
2105	Decreased, myelin basic protein expression in oligodendrocytes	Molecular	Feb 21, 2023	Feb 21, 2023	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
2111	Decreased, neural progenitor cell adhesion to laminin	Cellular	Feb 21, 2023	Feb 21, 2023	Binding to the extracellular protein laminin leading to decreased cognitive function
618	Decreased, Neuronal network function in adult brain	Organ	Nov 29, 2016	Sep 16, 2017	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality Various neuronal effects induced by elavl3, sox10, and mbp
1330	Decreased, neuroplasticity	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation Serotonin transporter activation to agitation Serotonin transporter activation to depression
193	Decreased, Nitric Oxide	Cellular	Nov 29, 2016	Sep 16, 2017	Calcium-mediated neuronal ROS production and energy imbalance
2116	Decreased, oligodendrocyte differentiation	Cellular	Feb 22, 2023	Feb 22, 2023	Unknown MIE altering cholesterol metabolism leading to decreased cognition Increased reactive oxygen species production leading to decreased cognitive function Inhibition of voltage-gated sodium channels leading to decreased cognition
1045	Decreased, Ovarian E2	Tissue	Nov 29, 2016	Sep 16, 2017	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
2074	Decreased, oxygen binding capacity by hemocyanin	Molecular	Nov 16, 2022	Nov 16, 2022	Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
1324	Decreased, packaged serotonin	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation SSRI (Selective serotonin reuptake inhibitor) to hypertension
216	Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway)	Cellular	Nov 29, 2016	Dec 3, 2016	AhR activation leading to hepatic steatosis
859	Decreased, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids	Molecular	Nov 29, 2016	Sep 16, 2017
2237	Decreased, Plasma sodium concentrations	Tissue	Jul 8, 2024	Sep 26, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
765	Decreased, population 1	Population	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to acute mortality
992	Decreased, Population 2		Nov 29, 2016	Nov 29, 2016
997	Decreased, Population size	Population	Nov 29, 2016	Dec 3, 2016	Deposition of ionizing energy leads to population decline via impaired meiosis
442	Decreased, Population trajectory	Population	Nov 29, 2016	Apr 18, 2017	Deposition of ionising energy leads to population decline via pollen abnormal Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
231	Decreased, PPAR-alpha activation	Molecular	Nov 29, 2016	Sep 16, 2017	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
232	Decreased, PPAR-beta activation	Molecular	Nov 29, 2016	Sep 16, 2017	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis
233	Decreased, PPAR-gamma activation	Molecular	Nov 29, 2016	Oct 30, 2023	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
858	Decreased, PPARalpha transactivation of gene expression	Molecular	Nov 29, 2016	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
749	Decreased, Progesterone from corpus luteum	Tissue	Nov 29, 2016	Sep 16, 2017	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
747	Decreased, Prolactin	Tissue	Nov 29, 2016	Sep 16, 2017	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
1104	Decreased, Prostaglandin F2alpha concentration, plasma	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
681	Decreased, Prostaglandin F2alpha synthesis, ovary	Organ	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
2113	Decreased, radial glia cell density	Cellular	Feb 21, 2023	Feb 21, 2023	Binding to the extracellular protein laminin leading to decreased cognitive function
1055	Decreased, Reduced estradiol in circulation decreases estrogen concentration at hypothalamus		Nov 29, 2016	Nov 29, 2016
825	Decreased, Renal ability to dilute urine	Organ	Nov 29, 2016	Dec 3, 2016	Kidney dysfunction by decreased thyroid hormone
820	Decreased, Renal plasma flow	Tissue	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
1141	Decreased, Reproductive Success	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
1327	Decreased, seizure	Individual	Apr 13, 2017	Apr 13, 2017
1317	Decreased, serotonin transporter activity	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation SSRI (Selective serotonin reuptake inhibitor) to hypertension
1022	Decreased, serum T4/T3	Tissue	Nov 29, 2016	Sep 16, 2017
629	Decreased, sheltering	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation
585	Decreased, Sodium conductance 1	Cellular	Nov 29, 2016	Sep 16, 2017	Sodium channel inhibition leading to reduced survival sodium channel inhibition leading to increased predation Sodium channel inhibition leading to congenital malformations Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
1176	Decreased, sodium conductance 2	Cellular	Nov 29, 2016	Dec 3, 2016	Sodium channel (Nav1.1) inhibition leading to population decline
821	Decreased, Sodium reabsorption	Organ	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
2236	Decreased, Sodium uptake in gills	Cellular	Jul 8, 2024	Sep 24, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
647	Decreased, steroidogenic protein expression	Cellular	Nov 29, 2016	Jul 16, 2024	Modulation of Adult Leydig Cell Function Subsequent to Proteomic Alterations in the Adult Leydig Cell Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
636	Decreased, survival	Population	Nov 29, 2016	Dec 3, 2016	Histamine (H2) receptor antagonism leading to reduced survival Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1325	Decreased, synaptic release	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation SSRI (Selective serotonin reuptake inhibitor) to hypertension
989	Decreased, synthesis and secretion of molting fluid proteases		Nov 29, 2016	Nov 29, 2016
994	Decreased, Synthesis of molting fluid proteases	Tissue	Nov 29, 2016	Dec 3, 2016
528	Decreased, Synthesis of NE	Cellular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
743	Decreased, Testosterone binding to androgen receptor (hypothalamus)	Molecular	Nov 29, 2016	Sep 16, 2017	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
2104	Decreased, thyroid hormone binding to thyroid hormone receptor	Molecular	Feb 21, 2023	Feb 21, 2023	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
1093	Decreased, Thyroxine (T4) in tissues	Tissue	Nov 29, 2016	Sep 3, 2020
1003	Decreased, Triiodothyronine (T3)	Tissue	Nov 29, 2016	Oct 7, 2022	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
1116	Decreased, Triiodothyronine (T3) in tissues	Tissue	Nov 29, 2016	Sep 1, 2020	Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
737	Decreased, Uptake of inorganic iodide	Cellular	Nov 29, 2016	Sep 16, 2017
304	Decreased, VegfR2		Nov 29, 2016	Nov 29, 2016
2147	Decreased, Viable Offspring	Individual	Jun 2, 2023	Apr 10, 2024	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone Essential element imbalance leads to reproductive failure via oxidative stress
1295	Defect of Embryogenesis	Tissue	Feb 15, 2017	Sep 16, 2017	Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
890	Degeneration of dopaminergic neurons of the nigrostriatal pathway	Organ	Nov 29, 2016	Mar 15, 2018	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Various neuronal effects induced by elavl3, sox10, and mbp
428	Delay, Developmental GABA shift	Cellular	Nov 29, 2016	Nov 29, 2016
2047	Delay, Ovarian maturation	Cellular	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
2267	Delayed neuropathy, increased	Individual	Oct 1, 2024	Oct 1, 2024	Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
532	Delayed, Ovulation	Individual	Nov 29, 2016	Dec 3, 2016	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
1140	Delayed, Sexual maturity	Individual	Nov 29, 2016	Dec 3, 2016
2266	Demyelination, increased	Cellular	Oct 1, 2024	Oct 1, 2024	Inhibition of neuropathy target esterase leading to delayed neuropathy via lysolecithin cell membrane integration Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
2142	Depletion, Ectoplasmic specialization (ES)	Cellular	May 17, 2023	May 17, 2023	Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1143	Depletion, energy reserves	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
130	Depletion, GSH	Cellular	Nov 29, 2016	Sep 14, 2023	Glutathione conjugation leading to reproductive dysfunction via oxidative stress
1482	Depletion, mtDNA	Cellular	Oct 25, 2017	Oct 25, 2017	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
1686	Deposition of Energy	Molecular	Aug 22, 2019	Aug 23, 2024	Deposition of energy leading to lung cancer Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Deposition of ionising energy leading to population decline via mitochondrial dysfunction Deposition of ionising energy leading to population decline via programmed cell death Deposition of ionising energy leads to population decline via pollen abnormal Deposition of energy leading to population decline via DNA strand breaks and follicular atresia Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and follicular atresia Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Deposition of energy leads to abnormal vascular remodeling Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin Deposition of energy leading to occurrence of cataracts Deposition of energy leading to occurrence of bone loss Deposition of Energy Leading to Learning and Memory Impairment
1550	Deposition of Ionizing Energy	Molecular	Dec 19, 2018	Dec 13, 2021	Deposition of ionizing energy leads to population decline via impaired meiosis
663	Desensitization, Nicotinic acetylcholine receptor	Molecular	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
2189	Development-related pathway alterations	Cellular	Sep 16, 2023	Sep 17, 2023
2035	development, liver cancer	Tissue	Jul 21, 2022	Jul 21, 2022
1272	Differentiation of Myofibroblast	Cellular	Feb 15, 2017	Feb 15, 2017
944	dimerization, AHR/ARNT	Molecular	Nov 29, 2016	Sep 16, 2017	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR AhR activation leading to preeclampsia Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
1869	Diminished protective oxidative stress response	Cellular	Apr 20, 2021	Oct 30, 2023	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation SARS-CoV-2 infection leading to hyperinflammation SARS-CoV-2 infection leading to pyroptosis Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Increased reactive oxygen species production leading to decreased cognitive function
652	Direct effects of Corticosterone on steroidogenesis, Decreased testosterone by adult Leydig cells	Cellular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
1958	Direct hERG channel blockage	Cellular	Dec 13, 2021	Dec 13, 2021
1260	Direct mitochondrial inhibition	Molecular	Feb 7, 2017	Sep 16, 2017	AOP from chemical insult to cell death
721	Disorganization, Meiotic Spindle	Cellular	Nov 29, 2016	Apr 20, 2021	Chemical binding to tubulin in oocytes leading to aneuploid offspring
1830	Displacement, Serum thyroxine (T4) from carrier protein	Molecular	Dec 9, 2020	Dec 9, 2020	Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
958	Displacement, Serum thyroxine (T4) from transthyretin	Molecular	Nov 29, 2016	Dec 17, 2016	Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
2110	Disrupted binding, laminin-beta1-integrin receptors with laminin	Molecular	Feb 21, 2023	Feb 21, 2023	Binding to the extracellular protein laminin leading to decreased cognitive function
2225	Disrupted Lipid Storage	Cellular	May 8, 2024	May 23, 2024	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
1882	Disrupted meiotic initiation of fetal oogonia of the ovary	Cellular	May 24, 2021	Feb 27, 2022	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
2227	Disrupted PPAR isoform nuclear signaling	Molecular	May 14, 2024	May 22, 2024	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
1977	Disruption of sodium channel gating kinetics	Cellular	Mar 15, 2022	Jul 24, 2024	Binding to voltage gate sodium channels during development leads to cognitive impairment Inhibition of voltage-gated sodium channels leading to decreased cognition
1983	Disruption, action potential generation	Cellular	Mar 31, 2022	Jul 24, 2024	Binding to voltage gate sodium channels during development leads to cognitive impairment
2141	Disruption, Estrogen receptor	Molecular	May 17, 2023	May 17, 2023	Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1536	Disruption, Intracellular calcium mobilization	Cellular	Jun 21, 2018	Jun 21, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
898	Disruption, Lysosome	Cellular	Nov 29, 2016	Aug 29, 2024	Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity Endocytic lysosomal uptake leading to liver fibrosis Endocytotic lysosomal uptake leads to intestinal barrier disruption
169	Disruption, Membrane integrity	Cellular	Nov 29, 2016	Sep 16, 2017	Narcosis leading to respiratory failure
720	Disruption, Microtubule dynamics	Molecular	Nov 29, 2016	Nov 7, 2019	Chemical binding to tubulin in oocytes leading to aneuploid offspring
178	Disruption, Mitochondrial electron transport chain	Cellular	Nov 29, 2016	Sep 16, 2017	Calcium-mediated neuronal ROS production and energy imbalance Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
1681	Disruption, Neural crest cell migration	Cellular	Aug 13, 2019	Aug 13, 2019	TBX1 inhibition leading to congenital cardiac conotruncal anomalies
2151	Disruption, neurotransmitter release	Molecular	Jun 27, 2023	Jul 21, 2023	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Various neuronal effects induced by elavl3, sox10, and mbp Binding and activation of GPER leading to learning and memory impairments
1682	Disruption, Progenitor cells of second heart field	Cellular	Aug 13, 2019	Feb 15, 2022	TBX1 inhibition leading to congenital cardiac conotruncal anomalies Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
1537	Disruption, Sarcomere assembly	Cellular	Jun 21, 2018	Jun 21, 2018	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility
1590	Distribution and deposition of chemicals to skin and/or eyes	Molecular	Feb 3, 2019	Feb 3, 2019
1581	Disturbance in microtubule dynamic instability	Cellular	Jan 29, 2019	Jan 29, 2019	Microtubule interacting drugs lead to peripheral neuropathy
831	Disturbance, Lysosomal function	Cellular	Nov 29, 2016	Sep 16, 2017	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity
2114	Disturbed, cortical architecture	Organ	Feb 21, 2023	Feb 21, 2023	Binding to the extracellular protein laminin leading to decreased cognitive function
2112	Disturbed, radial glia cell alignment and migration	Cellular	Feb 21, 2023	Feb 21, 2023	Binding to the extracellular protein laminin leading to decreased cognitive function
1388	Dopamine release in the brain, decreased	Tissue	May 2, 2017	May 17, 2017	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
472	Down Regulation, CPT1A	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
1286	Down Regulation, GSS and GSTs gene	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
131	Down Regulation, Gulcose-6-phosphate dehydrogenase	Cellular	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
474	Down Regulation, HMGCS2	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
427	Down Regulation, K-Cl co-transporter 2 (KCC2)	Cellular	Nov 29, 2016	Nov 29, 2016
1787	Downregulation, ACE2	Cellular	May 15, 2020	Mar 31, 2021	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
2088	Dysfunction of respiratory system	Individual	Jan 9, 2023	Jan 9, 2023	AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1184	Dysfunction, Mitochondrial Dynamics		Nov 29, 2016	Nov 29, 2016
1945	Dysfunctional Autophagy	Cellular	Oct 26, 2021	Oct 26, 2021	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Adverse outcome pathway of PM-induced respiratory toxicity
1850	dysgeusia	Organ	Mar 28, 2021	Apr 26, 2021	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
1703	Dysregulation of heart rate and vascular tone	Organ	Nov 25, 2019	Dec 20, 2019	Acetylcholinesterase inhibition leading to acute mortality
2224	Dysregulation of transcriptional expression within PPAR signaling network	Molecular	May 8, 2024	May 23, 2024	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
1854	Dysregulation, ACE2 expression and activity	Molecular	Mar 31, 2021	Feb 18, 2023	Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis Binding to ACE2 leading to lung fibrosis
1600	Eczematous eruption (Erythema, Papules, Vesicles, Pruritius, Weeping, Oozing, Crusting)	Organ	Feb 3, 2019	Feb 3, 2019
1248	EGFR , Activation		Nov 29, 2016	Nov 29, 2016
1247	EGFR , PPAR-alpha activation		Nov 29, 2016	Nov 29, 2016
222	Elimination of (high doses), Posterior cardinal vein		Nov 29, 2016	Nov 29, 2016
2011	Emphysema	Organ	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
1841	Encephalitis	Organ	Feb 23, 2021	Feb 23, 2021	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 Various neuronal effects induced by elavl3, sox10, and mbp
1539	Endocytotic lysosomal uptake	Molecular	Nov 6, 2018	Aug 29, 2024	Endocytic lysosomal uptake leading to liver fibrosis Endocytotic lysosomal uptake leads to intestinal barrier disruption
2017	Endoplasmic reticulum stress	Cellular	Jun 27, 2022	Jun 27, 2022	PM2.5-related AOP frameworks on liver diseases Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
2175	Endothelial cell death	Cellular	Aug 21, 2023	Aug 21, 2023
1913	Endothelial cell dysfunction	Cellular	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
2212	Epididymal agenesis	Organ	Mar 19, 2024	Jun 28, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
2152	Epigenetic modification process	Cellular	Jul 27, 2023	Jul 27, 2023	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
1457	Epithelial Mesenchymal Transition	Cellular	Jul 26, 2017	Apr 24, 2024	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis α-diketone-induced bronchiolitis obliterans Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway DNA damage and mutations leading to Metastatic Breast Cancer Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer Adverse outcome pathway of PM-induced respiratory toxicity Succinate dehydrogenase inactivation leading to cancer
2251	Estradiol availability, increased	Tissue	Aug 9, 2024	Aug 12, 2024
1180	Estrogen receptor activation,		Nov 29, 2016	Nov 29, 2016
2126	Estrogen receptor alpha inactivation	Molecular	Apr 5, 2023	Apr 10, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
1714	Exacerbation of systemic lupus erythematosus (SLE)	Individual	Dec 29, 2019	Aug 14, 2020	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
1859	Excitation of intracellular water	Molecular	Apr 11, 2021	Apr 11, 2021
1217	Excitation of trigeminal nerves induces Sensory Airway Irritation,	Organ	Nov 29, 2016	Sep 24, 2018
1273	Expression of Collagen	Cellular	Feb 15, 2017	Feb 15, 2017
2153	Expression of factors ruling proliferation, modified	Cellular	Jul 27, 2023	Jul 27, 2023	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
1905	eya1 expression, inhibited	Molecular	Jul 14, 2021	Oct 7, 2021	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
1559	Facial cartilage structures are reduced in size and morphologically distorted	Tissue	Dec 20, 2018	Dec 20, 2018	Histone deacetylase inhibition leads to impeded craniofacial development Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development
1131	Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin)	Molecular	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1119	Failure in gamma-glutamyl carboxylation of glutamine residues on clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin)		Nov 29, 2016	Nov 29, 2016
1130	Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage)	Organ	Nov 29, 2016	Sep 16, 2017	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1528	Fatty Acid Beta Oxidation, Decreased	Molecular	Jun 11, 2018	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
240	Feminisation or incomplete development, Primary and accessory male sex organs	Organ	Nov 29, 2016	Sep 16, 2017	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
2241	Ferroptosis related pathways activation	Cellular	Jul 9, 2024	Jul 9, 2024	Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
1866	Fibrinolysis, decreased	Molecular	Apr 20, 2021	Oct 19, 2021	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
2012	Fibroblast proliferation and differentiation	Cellular	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
1587	Fibroproliferative airway lesions	Tissue	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans
1442	Foam cell formation	Organ	Jun 29, 2017	Jun 29, 2017
1597	Formation of DNA photo-adducts	Cellular	Feb 3, 2019	Feb 3, 2019
1440	Formation of HDL-SAA	Cellular	Jun 29, 2017	Jun 29, 2017
1899	formation of neutrophil extracellular traps (NETs)	Cellular	Jul 8, 2021	Jul 8, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
1598	Formation of protein photo-adducts	Cellular	Feb 3, 2019	Feb 3, 2019
118	Formation, Formation of hemoglobin adducts	Cellular	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
856	Formation, Hepatocellular and Bile duct tumors	Organ	Nov 29, 2016	Sep 16, 2017	Sustained AhR Activation leading to Rodent Liver Tumours
840	Formation, Liver fibrosis	Tissue	Nov 29, 2016	Sep 16, 2017	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
347	Formation, Liver tumor	Individual	Nov 29, 2016	Dec 3, 2016	Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
839	Formation, Mallory body	Cellular	Nov 29, 2016	Dec 3, 2016	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
373	Formation, Pro-mutagenic DNA Adducts	Molecular	Nov 29, 2016	Sep 16, 2017	AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
976	Formation, The binding of FK506 with FKBP12	Molecular	Nov 29, 2016	Dec 3, 2016
1903	foxi1 expression, increased	Molecular	Jul 14, 2021	Oct 28, 2021	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
1911	FOXJ1 Protein, Decreased	Cellular	Jul 23, 2021	Sep 10, 2021	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
1646	Frizzled activation	Molecular	May 29, 2019	May 29, 2019
1668	Frustrated phagocytosis	Cellular	Jul 3, 2019	Sep 16, 2022	Frustrated phagocytosis-induced lung cancer Frustrated phagocytosis leads to malignant mesothelioma
1932	Gastrointestinal disorders	Individual	Sep 2, 2021	Sep 8, 2021
1513	General Apoptosis	Cellular	Apr 4, 2018	Oct 18, 2023	CYP2E1 activation and formation of protein adducts leading to neurodegeneration Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway
1236	Generation of novel epitopes , Antigen presentation	Cellular	Nov 29, 2016	Dec 3, 2016
682	Generation, Amplified excitatory postsynaptic potential (EPSP)	Cellular	Nov 29, 2016	May 18, 2018	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
1896	Genomic instability	Cellular	Jul 6, 2021	Jul 6, 2021	Frustrated phagocytosis leads to malignant mesothelioma Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
1953	Gestational diabetes mellitus	Individual	Nov 18, 2021	Nov 18, 2021	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
494	Glucocorticoid Receptor Agonist, Activation	Molecular	Nov 29, 2016	Sep 16, 2017	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
651	Glucocorticoid Receptor mediated alterations in steriodogenic enzymes, Decreased testosterone by adult Leydig cells	Cellular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
1488	Glutamate dyshomeostasis	Cellular	Nov 9, 2017	Jul 15, 2022	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
1290	Glutathione homeostasis	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
1287	Glutathione synthesis	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
2254	Gluten-reactive and transglutaminase 2 reactive B cell receptors, generation	Molecular	Aug 13, 2024	Sep 13, 2024	Gluten intake leading to celiac disease - under development
2256	Gluten-reactive B cells and transglutaminase 2-reactive B cells, activation and differentiation	Cellular	Aug 13, 2024	Sep 13, 2024	Gluten intake leading to celiac disease - under development
2260	Gluten-reactive CD4+ T cells, activation and proliferation	Cellular	Sep 13, 2024	Sep 13, 2024	Gluten intake leading to celiac disease - under development
2253	Gluten-reactive T cell receptors, generation	Molecular	Aug 13, 2024	Sep 13, 2024	Gluten intake leading to celiac disease - under development
1519	Glycolysis	Cellular	May 24, 2018	May 24, 2018
1800	Granulosa cell proliferation of gonadotropin-independent follicles, Reduced	Cellular	Oct 13, 2020	Apr 20, 2022	Androgen receptor (AR) antagonism leading to decreased fertility in females
1467	Growth, reduction	Individual	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1647	GSK3beta inactivation	Molecular	May 29, 2019	Oct 5, 2021	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
1954	Gut microbiota, alteration	Organ	Nov 30, 2021	Jan 4, 2022	Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
1535	Heart failure	Organ	Jun 19, 2018	Sep 27, 2024	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction. ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure. Decreased Sodium/Potassium ATPase activity leads to Heart failure
1412	Helicobacter pylori infection	Tissue	Jun 2, 2017	Jun 2, 2017	Helicobacter pylori to gastric ulcer
1124	Hemorrhage , Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal		Nov 29, 2016	Nov 29, 2016
1121	Hemorrhage , organ dysfunction, hypovolemic shock		Nov 29, 2016	Nov 29, 2016
1123	Hemorrhage, organ dysfunction, hypovolemic shock, Impaired oxygen delivery to tissue		Nov 29, 2016	Nov 29, 2016
1133	Hemostasis, Depletion from blood of fully functional carboxylated clotting factors	Tissue	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
2016	Hepatocyte cell apoptosis	Cellular	Jun 7, 2022	Jun 7, 2022
1393	Hepatocytotoxicity	Cellular	May 30, 2017	Jun 19, 2021	Cyp2E1 Activation Leading to Liver Cancer
1291	Hepatotoxicity	Cellular	Feb 15, 2017	Feb 15, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
1957	hERG channel biogenesis interference	Molecular	Dec 13, 2021	Dec 13, 2021
2099	hERG channel blockade	Molecular	Jan 29, 2023	Jan 29, 2023	hERG channel blockade leading to sudden cardiac death
757	Hippocampal anatomy, Altered	Tissue	Nov 29, 2016	Jul 24, 2024	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Binding to voltage gate sodium channels during development leads to cognitive impairment
756	Hippocampal gene expression, Altered	Tissue	Nov 29, 2016	Aug 11, 2018	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
758	Hippocampal Physiology, Altered	Tissue	Nov 29, 2016	Jul 24, 2024	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals Binding to voltage gate sodium channels during development leads to cognitive impairment
1503	Histone acetylation, increase	Cellular	Jan 21, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy Histone deacetylase inhibition leads to neural tube defects
1502	Histone deacetylase inhibition	Molecular	Jan 21, 2018	Jul 14, 2022	Histone deacetylase inhibition leading to testicular atrophy Histone deacetylase inhibition leads to impeded craniofacial development Histone deacetylase inhibition leads to neural tube defects Ceramide synthase inhibition leading to neural tube defects
2252	Human leukocyte antigen DQ2/8-gluten complexes, formation	Molecular	Aug 13, 2024	Sep 13, 2024	Gluten intake leading to celiac disease - under development
1853	Hyperactivation of ACE/Ang-II/AT1R axis	Molecular	Mar 31, 2021	Mar 31, 2021	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
1868	Hyperinflammation	Tissue	Apr 20, 2021	Dec 29, 2021	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation SARS-CoV-2 infection leading to hyperinflammation Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
1943	Hyperphosphorylation of Tau	Cellular	Oct 26, 2021	Oct 26, 2021	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
142	Hyperplasia, Hyperplasia	Tissue	Nov 29, 2016	Sep 16, 2017	Uncharacterized liver damage leading to hepatocellular carcinoma
415	Hyperplasia, Leydig cell	Cellular	Nov 29, 2016	Sep 27, 2017	PPARα activation leading to impaired fertility in adult male rodents
1078	Hyperplasia, Mammary gland	Tissue	Nov 29, 2016	Sep 16, 2017	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
1052	Hyperplasia, ovarian epithelium	Tissue	Nov 29, 2016	Sep 16, 2017	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
1051	Hyperplasia, ovarian stromal cells	Cellular	Nov 29, 2016	Sep 16, 2017	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
763	hyperpolarisation, neuron	Cellular	Nov 29, 2016	Sep 16, 2017	Glutamate-gated chloride channel activation leading to acute mortality Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
943	Hypersecretion, Mucus	Organ	Nov 29, 2016	Nov 29, 2016
952	Hypertension	Individual	Nov 29, 2016	Sep 27, 2017	Peptide Oxidation Leading to Hypertension Na+ /K+ -ATPase inhibition leading to hypertension
1043	Hypertrophy/hyperplasia, smooth muscle	Cellular	Nov 29, 2016	Dec 3, 2016	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
1095	hyperuricemia,		Nov 29, 2016	Nov 29, 2016
2107	Hypomyelination	Tissue	Feb 21, 2023	Feb 21, 2023	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition Unknown MIE altering cholesterol metabolism leading to decreased cognition Increased reactive oxygen species production leading to decreased cognitive function Inhibition of voltage-gated sodium channels leading to decreased cognition Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
2082	Hypospadias, increased	Organ	Dec 18, 2022	Jul 16, 2024	Androgen receptor (AR) antagonism leading to hypospadias in male offspring Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
1819	IFNγ signaling	Cellular	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
1856	Imbalanced salty and sweet taste responses	Tissue	Apr 7, 2021	Apr 7, 2021	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
1818	Immune cell activation	Cellular	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
2180	Immune mechanisms antagonized by viral proteins	Molecular	Aug 23, 2023	Dec 13, 2023	Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
1820	Immune mediated hepatitis	Organ	Nov 2, 2020	Nov 2, 2020	Immune mediated hepatitis
1225	Immune system inflammation	Tissue	Nov 29, 2016	Sep 16, 2017
1644	Impaired Ab production	Cellular	May 23, 2019	Jun 25, 2019
1568	Impaired antigen presentation	Organ	Dec 24, 2018	Dec 24, 2018
1582	Impaired axonial transport	Cellular	Jan 29, 2019	Jan 29, 2019	Microtubule interacting drugs lead to peripheral neuropathy A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Various neuronal effects induced by elavl3, sox10, and mbp
1705	Impaired coordination and movement	Individual	Dec 20, 2019	Dec 20, 2019	Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement
364	Impaired development of, Reproductive organs	Individual	Nov 29, 2016	Dec 3, 2016	Estrogen receptor agonism leading to reproductive dysfunction Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
1849	Impaired gustatory nerve	Tissue	Mar 28, 2021	Apr 7, 2021	Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
1572	Impaired IL-1 signaling	Molecular	Dec 24, 2018	Jun 24, 2019
1700	Impaired IL-1R1 signaling in T cell	Molecular	Nov 17, 2019	Mar 2, 2023	Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
1615	Impaired inguinoscrotal testicular descent phase	Organ	Apr 10, 2019	Jul 18, 2024	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
2144	Impaired insulin signaling	Cellular	May 25, 2023	May 25, 2023	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
1833	Impaired lung function	Individual	Jan 8, 2021	Feb 16, 2021
1946	Impaired mechanotransduction of pericytes	Cellular	Oct 28, 2021	Oct 28, 2021	SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
1873	impaired olfactory function (anosmia)	Organ	Apr 25, 2021	Mar 30, 2022	SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
1695	Impaired ovulation	Organ	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
1125	Impaired oxygen and nutrient delivery to tissue, impaired removal of carbon dioxide and other waste products, Hemorrhage, organ dysfunction and hypovolemic shock		Nov 29, 2016	Nov 29, 2016
1678	Impaired oxygenation of the blood	Organ	Jul 3, 2019	Jul 3, 2019
2179	Impaired Platelet Aggregation	Tissue	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
1136	Impaired recruitment , Population trajectory	Population	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1569	Impaired T cell activation	Cellular	Dec 24, 2018	Jun 25, 2019
2080	Impaired, blood testis barrier	Organ	Dec 13, 2022	Dec 13, 2022	Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
577	impaired, Development	Individual	Nov 29, 2016	Dec 3, 2016	Suppression of immune system contributes to impaired development and leads to colony loss/failure
406	impaired, Fertility	Individual	Nov 29, 2016	Sep 14, 2023	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female PPARα activation leading to impaired fertility in adult male rodents PPARα activation in utero leading to impaired fertility in males Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory Inhibition of 11β-hydroxylase leading to decresed population trajectory Deposition of ionizing energy leads to population decline via impaired meiosis Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary Glutathione conjugation leading to reproductive dysfunction via oxidative stress Androgen receptor (AR) antagonism leading to decreased fertility in females
568	impaired, Hive thermoregulation	Population	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure Suppression of immune system contributes to impaired development and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure
697	impaired, ion channels	Cellular	Nov 29, 2016	Dec 3, 2016	Altered ion channel activity leading impaired heart function
566	impaired, Larval development	Population	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
637	impaired, Learning and memory	Individual	Nov 29, 2016	Dec 3, 2016	Various neuronal effects induced by elavl3, sox10, and mbp
2106	Impaired, oligodendrocyte maturation	Cellular	Feb 21, 2023	Feb 21, 2023	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition
1989	Impaired, Oocyte maturation and ovulation	Tissue	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
889	Impaired, Proteostasis	Cellular	Nov 29, 2016	Mar 15, 2018	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Mitochondrial complex inhibition leading to liver injury
1991	Impaired, Reproduction	Population	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
1758	Impaired, Spermatogenesis	Organ	Apr 16, 2020	Apr 10, 2024	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory Essential element imbalance leads to reproductive failure via oxidative stress Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis
583	impaired, Thoracic shivering	Individual	Nov 29, 2016	Dec 3, 2016
2213	Impaired, urethral tube closure	Organ	Mar 19, 2024	Jun 28, 2024	Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased
1667	Impaired,anterior-posterior axis development	Individual	Jul 3, 2019	Jul 3, 2019	Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
1719	Impairment of T-cell dependent antibody response	Individual	Jan 5, 2020	Feb 24, 2021	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
986	Impairment of TDAR	Individual	Nov 29, 2016	Mar 2, 2023
110	Impairment, Endothelial network	Cellular	Nov 29, 2016	Jan 18, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
1683	Impairment, Fourth pharyngeal arch development	Tissue	Aug 13, 2019	Aug 13, 2019	TBX1 inhibition leading to congenital cardiac conotruncal anomalies
341	Impairment, Learning and memory	Individual	Nov 29, 2016	Jul 26, 2024	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2 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 Histamine (H2) receptor antagonism leading to reduced survival 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 Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons Deposition of Energy Leading to Learning and Memory Impairment Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory Binding and activation of GPER leading to learning and memory impairments
984	Impairment, T-cell dependent antibody response	Individual	Nov 29, 2016	Feb 19, 2023	Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
1328	Inactivated, 5-HTR (serotonin receptors)	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation Serotonin transporter activation to agitation Serotonin transporter activation to depression
1270	Inactivation of PPARγ	Molecular	Feb 15, 2017	Dec 26, 2017	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1356	Inactive, membrane depolarization	Molecular	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
155	Inadequate DNA repair	Cellular	Nov 29, 2016	Mar 8, 2024	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations Alkylation of DNA leading to cancer 2 Alkylation of DNA leading to cancer 1 Oxidative DNA damage leading to chromosomal aberrations and mutations Deposition of energy leading to lung cancer Alkylation of DNA leading to reduced sperm count Bulky DNA adducts leading to mutations Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia DNA damage and mutations leading to Metastatic Breast Cancer Deposition of energy leading to occurrence of cataracts
1552	Inadequate DNA repair (deprecated, please use https://aopwiki.org/events/155)	Molecular	Dec 19, 2018	Jan 25, 2019
1555	Increase cell proliferation	Cellular	Dec 19, 2018	Dec 19, 2018	AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
1554	Increase Chromosomal Aberrations	Molecular	Dec 19, 2018	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
1633	Increase in inflammation	Tissue	May 3, 2019	May 3, 2019	Immune mediated hepatitis Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
1632	Increase in reactive oxygen and nitrogen species (RONS)	Molecular	May 3, 2019	May 8, 2019	Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
1553	Increase mutations	Molecular	Dec 19, 2018	Dec 19, 2018	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
1713	Increase of anti-DNA antibody from autoreactive B cell	Cellular	Dec 29, 2019	Aug 14, 2020	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
1712	Increase of Th2 cells producing IL-4	Cellular	Dec 29, 2019	Aug 14, 2020	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
2073	increase oxidation of the di-copper moiety of the hemocyanin active site	Molecular	Nov 16, 2022	Nov 16, 2022	Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
1743	Increase plasma Ang II	Tissue	Mar 10, 2020	Mar 10, 2020	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
416	Increase proliferation, Leydig cell	Cellular	Nov 29, 2016	Sep 16, 2017	PPARα activation leading to impaired fertility in adult male rodents
1978	Increase risk, microcephaly	Individual	Mar 17, 2022	Mar 18, 2022	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
2056	Increase, delay in oviposition	Individual	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2054	Increase, impairment of cuticle sclerotization	Individual	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2055	Increase, pigmentation	Individual	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2098	Increase, Abnormal Neural Remodeling	Tissue	Jan 25, 2023	Jul 26, 2024	Deposition of Energy Leading to Learning and Memory Impairment
1768	Increase, Abnormal osmoregulation	Tissue	Apr 30, 2020	Aug 6, 2024	Excessive reactive oxygen species production leading to mortality (1)
736	Increase, Adenomas/carcinomas (bronchioloalveolar)	Tissue	Nov 29, 2016	Sep 16, 2017	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
741	Increase, Adenomas/carcinomas (follicular cell)	Tissue	Nov 29, 2016	Sep 16, 2017	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
713	Increase, Adenomas/carcinomas (renal tubular)	Tissue	Nov 29, 2016	Sep 16, 2017	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat) Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
797	Increase, Adenomas/carcinomas (urothelial)	Tissue	Nov 29, 2016	Sep 16, 2017	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
2045	Increase, Alcohol dehydrogenase	Molecular	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
313	Increase, Allergic Respiratory Hypersensitivity Response	Organ	Nov 29, 2016	Feb 7, 2023	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response
1384	Increase, ammonium (NH4+)	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation Helicobacter pylori to gastric ulcer
2134	Increase, Androgen receptor	Molecular	May 11, 2023	May 11, 2023	Androgen receptor activation leading to prostate cancer
728	Increase, Aneuploid offspring	Individual	Nov 29, 2016	May 27, 2019	Chemical binding to tubulin in oocytes leading to aneuploid offspring
1376	Increase, angiogenesis	Tissue	Apr 17, 2017	Feb 29, 2024	Gastric ulcer formation Activation of the AhR leading to metastatic breast cancer Succinate dehydrogenase inactivation leading to cancer
1365	Increase, Apoptosis	Cellular	Apr 15, 2017	Apr 15, 2017	Alkylation of DNA leading to reduced sperm count Formation of DNA photoproducts leading to growth inhibition (1) Thermal stress leading to population decline (3) Thermal stress leading to population decline (2) Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction Excessive reactive oxygen species production leading to mortality (4)
1372	Increase, bicarbonate	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
401	Increase, Biliary excretion TH glucuronide	Organ	Nov 29, 2016	Sep 16, 2017
1769	Increase, Body fluid overload	Tissue	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (1)
2048	Increase, Body volume of female adults	Individual	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
2090	Increase, Bone Remodeling	Tissue	Jan 11, 2023	Aug 13, 2024	Deposition of energy leading to occurrence of bone loss
50	Increase, Ca++ (intracellular)	Cellular	Nov 29, 2016	Sep 16, 2017	Calcium-mediated neuronal ROS production and energy imbalance
885	Increase, Cancer	Tissue	Nov 29, 2016	Aug 22, 2023	Alkylation of DNA leading to cancer 2 Alkylation of DNA leading to cancer 1 Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress Succinate dehydrogenase inactivation leading to cancer
2084	Increase, Cardiac remodelling	Tissue	Jan 5, 2023	Jan 5, 2023	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress
1774	Increase, Caspase transcription	Molecular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (3) DNA methyltransferase inhibition leading to population decline (4)
1779	Increase, Caspase transcription (F3)	Molecular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2)
1825	Increase, Cell death	Cellular	Dec 4, 2020	Aug 23, 2024	Mitochondrial ATP synthase antagonism leading to growth inhibition (2) Mitochondrial complex III antagonism leading to growth inhibition (2) Cytochrome oxidase inhibition leading to olfactory nasal lesions Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) GSK3beta inactivation leading to increased mortality via defects in developing inner ear Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death) Deposition of energy leading to occurrence of bone loss
55	Increase, Cell injury/death	Cellular	Nov 29, 2016	May 27, 2024	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Protein Alkylation leading to Liver Fibrosis 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 Endocytic lysosomal uptake leading to liver fibrosis 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 IKK complex inhibition leading to liver injury Acetylcholinesterase Inhibition Leading to Neurodegeneration Mitochondrial complex inhibition leading to liver injury Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms AhR activation leading to liver fibrosis Endocytotic lysosomal uptake leads to intestinal barrier disruption
1527	Increase, Cell membrane depolarization	Cellular	May 24, 2018	May 24, 2018	S-adenosylmethionine depletion leading to population decline (2) Sulfonylureareceptor binding leading to mortality Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity
870	Increase, Cell Proliferation	Cellular	Nov 29, 2016	Mar 8, 2024	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors Frustrated phagocytosis-induced lung cancer Deposition of energy leading to lung cancer Frustrated phagocytosis leads to malignant mesothelioma Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia Interaction with lung resident cell membrane components leads to lung cancer Deposition of energy leading to occurrence of cataracts
1182	Increase, Cell Proliferation (Epithelial Cells)	Cellular	Nov 29, 2016	May 8, 2019	Estrogen receptor activation leading to breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Increased DNA damage leading to increased risk of breast cancer
716	Increase, cell proliferation (hepatocytes)	Cellular	Nov 29, 2016	Jan 6, 2021	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat) PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
1636	Increase, Chromosomal aberrations	Cellular	May 19, 2019	Mar 8, 2024	Oxidative DNA damage leading to chromosomal aberrations and mutations Deposition of energy leading to lung cancer Deposition of energy leading to occurrence of cataracts
621	Increase, cilia movement	Tissue	Nov 29, 2016	Jan 13, 2017	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
1171	Increase, Clonal Expansion of Altered Hepatic Foci	Cellular	Nov 29, 2016	Jan 6, 2021	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
2195	Increase, CNS Neural cell death	Cellular	Oct 17, 2023	Oct 17, 2023	Various neuronal effects induced by elavl3, sox10, and mbp
1334	Increase, cortisone	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
1269	Increase, COX-2 expression	Molecular	Feb 9, 2017	Mar 20, 2018	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
1759	Increase, Cripto-1 expression	Cellular	Apr 20, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
320	Increase, Curved body axis		Nov 29, 2016	Nov 29, 2016
1812	Increase, Cytochrome c release	Cellular	Nov 2, 2020	Nov 2, 2020	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
2064	Increase, Cytosolic calcium	Cellular	Sep 13, 2022	Sep 13, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium
1305	Increase, cytosolic fatty acid	Cellular	Apr 12, 2017	Nov 27, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
768	Increase, Cytotoxicity	Cellular	Nov 29, 2016	Sep 16, 2017	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat) Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
770	Increase, Cytotoxicity (club cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
776	Increase, Cytotoxicity (corneal cells)	Cellular	Nov 29, 2016	Sep 16, 2017	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
780	Increase, Cytotoxicity (epithelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat) Interaction with lung resident cell membrane components leads to lung cancer
786	Increase, Cytotoxicity (hepatocytes)	Cellular	Nov 29, 2016	Sep 16, 2017	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
709	Increase, Cytotoxicity (renal tubular cell)	Cellular	Nov 29, 2016	Mar 3, 2022	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat) Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity Renal protein alkylation leading to kidney toxicity Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity
783	Increase, Cytotoxicity (tubular epithelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
794	Increase, Cytotoxicity (urothelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
1516	Increase, D1 protein antagonism	Molecular	May 24, 2018	Oct 7, 2020
1861	Increase, D1 protein deactivation	Cellular	Apr 11, 2021	Apr 11, 2021	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis
2053	Increase, Defects in tanning of new cuticle	Individual	Aug 28, 2022	Aug 28, 2022	Doda decarboxylase leading to mortality
2050	Increase, developmental abnormalities	Individual	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction Knickkopf leading to mortality
1456	Increase, Differentiation of fibroblasts	Cellular	Jul 26, 2017	Jul 26, 2017	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis
1194	Increase, DNA damage	Molecular	Nov 29, 2016	May 8, 2019	Estrogen receptor activation leading to breast cancer Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Deposition of ionizing energy leads to population decline via impaired meiosis Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia Deposition of ionising energy leading to population decline via programmed cell death Deposition of ionising energy leads to population decline via pollen abnormal Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1461	Increase, DNA double-strand breaks	Molecular	Aug 2, 2017	Nov 13, 2023	Inhibitor binding to topoisomerase II leading to infant leukaemia DNA methyltransferase inhibition leading to population decline (4) Formation of DNA photoproducts leading to growth inhibition (1) DNA methyltransferase inhibition leading to population decline (3) Excessive reactive oxygen species production leading to mortality (4)
1620	Increase, DNA hypomethylation	Molecular	Apr 22, 2019	Apr 22, 2019
1697	Increase, DNA methyltransferase expression	Molecular	Oct 30, 2019	Oct 30, 2019	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
1619	Increase, DNA methyltransferase inhibition	Molecular	Apr 22, 2019	Apr 22, 2019	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (3) DNA methyltransferase inhibition leading to population decline (4) DNA methyltransferase inhibition leading to transgenerational effects (1) DNA methyltransferase inhibition leading to transgenerational effects (2) Succinate dehydrogenase inactivation leading to cancer
1635	Increase, DNA strand breaks	Molecular	May 19, 2019	Aug 26, 2024	Oxidative DNA damage leading to chromosomal aberrations and mutations Deposition of energy leading to lung cancer Alkylation of DNA leading to reduced sperm count Deposition of energy leading to population decline via DNA strand breaks and follicular atresia Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Deposition of energy leading to occurrence of cataracts Deposition of Energy Leading to Learning and Memory Impairment Deposition of energy leads to abnormal vascular remodeling
746	Increase, Dopaminergic activity	Cellular	Nov 29, 2016	Sep 16, 2017	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
947	Increase, Early Life Stage Mortality	Individual	Nov 29, 2016	Mar 22, 2018	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2 Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
103	Increase, Ecdysone receptor agonism	Molecular	Nov 29, 2016	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
773	Increase, Endometrial adenocarcinomas	Tissue	Nov 29, 2016	Sep 16, 2017	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)
2068	Increase, Endothelial Dysfunction	Tissue	Sep 28, 2022	Aug 26, 2024	Deposition of energy leads to abnormal vascular remodeling
573	Increase, Energetic demands and therefore metabolic stress	Individual	Nov 29, 2016	Dec 3, 2016	Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
1860	Increase, Excitation of intracellular water	Molecular	Apr 11, 2021	Apr 11, 2021
115	Increase, FA Influx	Cellular	Nov 29, 2016	Mar 29, 2024	LXR activation leading to hepatic steatosis Pregnane X Receptor (PXR) activation leads to liver steatosis
1312	Increase, Fatty acid beta-oxidation	Cellular	Apr 13, 2017	Dec 4, 2020
1994	Increase, Ferroptosis	Cellular	Apr 7, 2022	Apr 7, 2022
1444	Increase, Follicular atresia	Organ	Jun 29, 2017	Nov 25, 2020	Deposition of energy leading to population decline via DNA strand breaks and follicular atresia Deposition of energy leading to population decline via DNA oxidation and follicular atresia
1765	Increase, Formation of DNA photoproducts	Molecular	Apr 30, 2020	Apr 30, 2020	Formation of DNA photoproducts leading to growth inhibition (1)
1265	Increase, Fushi tarazu factor-1 gene expression	Molecular	Feb 9, 2017	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
1361	Increase, GABA	Molecular	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
1621	Increase, Gene expression	Molecular	Apr 22, 2019	Apr 22, 2019
1175	Increase, Genes involved in fatty acid oxidation	Cellular	Nov 29, 2016	Dec 3, 2016
1827	Increase, Global DNA methylation	Molecular	Dec 4, 2020	Dec 4, 2020	Thermal stress leading to population decline (3)
2133	Increase, Glucuronidation of T4	Molecular	Apr 12, 2023	Apr 12, 2023
2070	Increase, Glycolysis	Cellular	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion
2117	Increase, goblet cell number	Cellular	Mar 8, 2023	Mar 8, 2023	EGFR Activation Leading to Decreased Lung Function
2137	Increase, Gonadotropins concentration in plasma	Tissue	May 16, 2023	May 16, 2023	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
1480	Increase, Growth hormone	Organ	Oct 10, 2017	Feb 16, 2021
2076	Increase, hemocyanin mRNA	Tissue	Nov 16, 2022	Nov 16, 2022	Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
719	Increase, hepatocellular adenomas and carcinomas	Tissue	Nov 29, 2016	Dec 26, 2020	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat) Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat) Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat) PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
336	Increase, Heritable mutations in offspring	Individual	Nov 29, 2016	Nov 29, 2016	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations
1698	Increase, hypermethylation of the promotor region of gonadotropin releasing hormone receptor	Molecular	Oct 30, 2019	Oct 30, 2019	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR
740	Increase, Hyperplasia (follicular cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
782	Increase, Hyperplasia (forestomach epithelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
772	Increase, Hyperplasia (glandular epithelial cells of endometrium)	Cellular	Nov 29, 2016	Sep 16, 2017	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat) Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
744	Increase, Hyperplasia (Leydig cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat) Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
767	Increase, Hyperplasia (renal tubular cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
735	Increase, Hyperplasia (terminal bronchiolar cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
784	Increase, Hyperplasia (tubular epithelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
796	Increase, Hyperplasia (urothelial)	Cellular	Nov 29, 2016	Sep 16, 2017	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat) AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
1343	Increase, hypertension	Individual	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
739	Increase, Hypertrophy and proliferation (follicular cell)	Cellular	Nov 29, 2016	Sep 16, 2017	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse
1707	Increase, IL-23 from matured dendritic cells	Cellular	Dec 27, 2019	Nov 23, 2020	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
990	Increase, Incomplete ecdysis	Individual	Nov 29, 2016	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality Doda decarboxylase leading to mortality Knickkopf leading to mortality
149	Increase, Inflammation	Cellular	Nov 29, 2016	Feb 28, 2024	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat) Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis α-diketone-induced bronchiolitis obliterans Activation of the AhR leading to metastatic breast cancer Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation
777	Increase, Inflammation (corneal cells)	Cellular	Nov 29, 2016	Sep 16, 2017	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
1338	Increase, inositol triphosphate	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
1296	Increase, insulin	Molecular	Apr 12, 2017	Apr 12, 2017
1339	Increase, intracellular calcium	Cellular	Apr 13, 2017	Jul 21, 2023	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
1378	Increase, leukocyte adherence	Tissue	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
745	Increase, Leydig cell tumors	Cellular	Nov 29, 2016	Sep 16, 2017	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat) Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
1445	Increase, Lipid peroxidation	Molecular	Jun 29, 2017	May 27, 2024	Excessive reactive oxygen species production leading to mortality (3) Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure Glutathione conjugation leading to reproductive dysfunction via oxidative stress Essential element imbalance leads to reproductive failure via oxidative stress
161	Increase, Liver and splenic hemosiderosis	Organ	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
1556	Increase, lung cancer	Organ	Dec 19, 2018	Jan 10, 2023	Deposition of energy leading to lung cancer
414	Increase, Luteinizing hormone (LH)	Cellular	Nov 29, 2016	Sep 16, 2017	PPARα activation leading to impaired fertility in adult male rodents
1333	Increase, mental stress	Individual	Apr 13, 2017	Apr 13, 2017
1785	Increase, Mitochondrial ATP synthase antagonism	Molecular	May 8, 2020	Dec 4, 2020	Mitochondrial ATP synthase antagonism leading to growth inhibition (1) Mitochondrial ATP synthase antagonism leading to growth inhibition (2)
1813	Increase, Mitochondrial complex I dysfunction	Molecular	Nov 2, 2020	Nov 2, 2020
1542	Increase, Mitochondrial complex III antagonism	Molecular	Dec 19, 2018	Dec 4, 2020	Mitochondrial complex inhibition leading to liver injury Mitochondrial complex III antagonism leading to growth inhibition (1) Mitochondrial complex III antagonism leading to growth inhibition (2)
1811	Increase, Mitochondrial complex III dysfunction	Molecular	Nov 2, 2020	Nov 2, 2020
2072	Increase, Mitochondrial swelling	Cellular	Nov 1, 2022	Nov 1, 2022	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling
350	Increase, Mortality	Individual	Nov 29, 2016	Oct 26, 2020	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality Formation of DNA photoproducts leading to growth inhibition (1) Excessive reactive oxygen species production leading to mortality (1) Excessive reactive oxygen species production leading to mortality (2) Excessive reactive oxygen species production leading to mortality (3) S-adenosylmethionine depletion leading to population decline (2) S-adenosylmethionine depletion leading to population decline (1) Chitinase inhibition leading to mortality Chitobiase inhibition leading to mortality Chitin synthase 1 inhibition leading to mortality Sulfonylureareceptor binding leading to mortality Alcohol dehydrogenase leading to reproductive dysfunction Doda decarboxylase leading to mortality Knickkopf leading to mortality Various neuronal effects induced by elavl3, sox10, and mbp Excessive reactive oxygen species production leading to mortality (4)
962	Increase, Mucin production	Cellular	Nov 29, 2016	Mar 9, 2023	EGFR Activation Leading to Decreased Lung Function
1374	Increase, mucosal blood flow	Tissue	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1373	Increase, mucous	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
185	Increase, Mutations	Molecular	Nov 29, 2016	May 15, 2023	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations Alkylation of DNA leading to cancer 2 Alkylation of DNA leading to cancer 1 Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Increased DNA damage leading to increased risk of breast cancer Oxidative DNA damage leading to chromosomal aberrations and mutations Deposition of energy leading to lung cancer Bulky DNA adducts leading to mutations DNA damage and mutations leading to Metastatic Breast Cancer Deposition of energy leading to occurrence of cataracts
876	Increase, Mutations in Critical Genes	Molecular	Nov 29, 2016	Sep 16, 2017	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
1341	Increase, myosin light chain phosphorylation	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
1607	Increase, Necrosis	Tissue	Mar 19, 2019	Mar 19, 2019	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
733	Increase, Necrosis (terminal bronchiolar cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
1578	Increase, Necrotic tissue	Tissue	Jan 7, 2019	Jan 7, 2019
1264	Increase, Nuclear receptor E75b gene expression	Molecular	Feb 9, 2017	May 24, 2018	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality
1775	Increase, Oocyte apoptosis	Cellular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (1) DNA methyltransferase inhibition leading to population decline (3) Deposition of ionizing energy leads to population decline via impaired meiosis Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis
1780	Increase, Oocyte apoptosis (F3)	Cellular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (1)
1526	Increase, Opening of voltage-dependent calcium channel	Cellular	May 24, 2018	May 24, 2018	S-adenosylmethionine depletion leading to population decline (2) Sulfonylureareceptor binding leading to mortality
1777	Increase, Ovarian follicle breakdown	Organ	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (4)
1784	Increase, Ovarian follicle breakdown (F3)	Organ	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (2)
1776	Increase, Ovarian somatic cell apoptosis	Cellular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to population decline (2) DNA methyltransferase inhibition leading to population decline (4)
1783	Increase, Ovarian somatic cell apoptosis (F3)	Cellular	Apr 30, 2020	Apr 30, 2020	DNA methyltransferase inhibition leading to transgenerational effects (2)
1634	Increase, Oxidative damage to DNA	Molecular	May 19, 2019	Mar 8, 2024	Oxidative DNA damage leading to chromosomal aberrations and mutations Deposition of energy leading to population decline via DNA oxidation and follicular atresia Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Deposition of energy leading to occurrence of cataracts Excessive reactive oxygen species production leading to mortality (4) Thermal stress leading to population decline (2)
1608	Increase, Oxidative DNA damage	Molecular	Mar 19, 2019	Mar 19, 2019
769	Increase, Oxidative metabolism	Cellular	Nov 29, 2016	Dec 3, 2016	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
1969	Increase, Oxidative Stress	Molecular	Feb 4, 2022	Mar 3, 2022
1279	Increase, Oxidative Stress / Activation, PMK-1 P38 MAPK	Cellular	Feb 15, 2017	Sep 16, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
1826	Increase, Oxygen consumption	Cellular	Dec 4, 2020	Dec 4, 2020
1865	Increase, Oxygen-evolving complex damage	Molecular	Apr 11, 2021	Apr 11, 2021	Oxygen-evolving complex damage leading to population decline via inhibition of photosynthesis
779	Increase, Papillomas/carcinomas (squamous cells)	Cellular	Nov 29, 2016	Sep 16, 2017	HPPD inhibition leading to corneal papillomas and carcinomas (in rat) Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
358	Increase, Pericardial edema	Organ	Nov 29, 2016	Sep 16, 2017
1173	Increase, Peroxisomal Fatty Acid Beta Oxidation of Fatty Acids	Molecular	Nov 29, 2016	Dec 3, 2016
1170	Increase, Phenotypic enzyme activity	Cellular	Nov 29, 2016	Dec 28, 2020	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents
1892	increase, placental insufficiency	Organ	May 31, 2021	May 31, 2021	AhR activation leading to preeclampsia
220	Increase, Plasma vitellogenin concentrations	Organ	Nov 29, 2016	Jun 24, 2024	Estrogen receptor agonism leading to reproductive dysfunction ER agonism leading to reduced survival due to renal failure Estrogen receptor agonism leading to reduced survival and population growth due to renal failure Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
1375	Increase, platelet aggregation	Tissue	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1993	Increase, Pneumonia	Organ	Apr 7, 2022	Apr 7, 2022
1965	Increase, Pollen abnormal	Organ	Jan 13, 2022	Jan 13, 2022	Deposition of ionising energy leads to population decline via pollen abnormal
623	Increase, predation	Population	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
1893	increase, Preeclampsia	Individual	May 31, 2021	May 31, 2021	AhR activation leading to preeclampsia
1524	Increase, Premature molting	Individual	May 24, 2018	Feb 17, 2021	S-adenosylmethionine depletion leading to population decline (2) S-adenosylmethionine depletion leading to population decline (1) Chitinase inhibition leading to mortality Chitobiase inhibition leading to mortality Chitin synthase 1 inhibition leading to mortality Sulfonylureareceptor binding leading to mortality
774	Increase, Preneoplastic foci (hepatocytes)	Cellular	Nov 29, 2016	Sep 16, 2017	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat) Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
2097	Increase, Pro-Inflammatory Mediators	Tissue	Jan 25, 2023	Jul 26, 2024	Deposition of Energy Leading to Learning and Memory Impairment
1864	Increase, Programmed cell death	Cellular	Apr 11, 2021	Apr 12, 2021	Deposition of ionising energy leading to population decline via programmed cell death
1579	Increase, proinflammatory mediators (TNFalpha)	Molecular	Jan 7, 2019	Jan 7, 2019	IKK complex inhibition leading to liver injury
923	Increase, Proliferation of goblet cells	Cellular	Nov 29, 2016	Aug 20, 2021
1767	Increase, Protein oxidation	Molecular	Apr 30, 2020	Apr 30, 2020	Excessive reactive oxygen species production leading to mortality (1)
2077	Increase, pulmonate breathing	Individual	Nov 16, 2022	Nov 16, 2022	Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin
246	Increase, RBC congestion in liver	Organ	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
1364	Increase, Reactive oxygen species	Molecular	Apr 15, 2017	Mar 19, 2019	Thermal stress leading to population decline (2) Deposition of ionizing energy leads to population decline via impaired meiosis AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. AhR activation leading to liver fibrosis
257	Increase, Reactive Oxygen Species production	Molecular	Nov 29, 2016	Apr 11, 2021	Calcium-mediated neuronal ROS production and energy imbalance Excessive reactive oxygen species production leading to mortality (1) Excessive reactive oxygen species production leading to mortality (2) Excessive reactive oxygen species production leading to mortality (3) Excessive reactive oxygen species production leading to mortality (4) Thermal stress leading to population decline (3) Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and follicular atresia Increased reactive oxygen species production leading to decreased cognitive function The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
778	Increase, Regenerative cell proliferation (corneal cells)	Cellular	Nov 29, 2016	Sep 16, 2017	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
781	Increase, Regenerative cell proliferation (forestomach epithelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)
787	Increase, Regenerative cell proliferation (hepatocytes)	Cellular	Nov 29, 2016	Sep 16, 2017	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)
734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)	Cellular	Nov 29, 2016	Dec 3, 2016	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)
710	Increase, Regenerative cell proliferation (tubular epithelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat) Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
795	Increase, Regenerative cell proliferation (urothelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat) AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
252	Increase, Renal pathology due to VTG deposition	Organ	Nov 29, 2016	Jun 24, 2024	Estrogen receptor agonism leading to reproductive dysfunction Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
869	Increase, Respiratory or Squamous Metaplasia	Tissue	Nov 29, 2016	Sep 29, 2017	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
1652	Increase, S-adenosylmethionine depletion	Molecular	May 30, 2019	May 30, 2019
1348	Increase, seizure	Individual	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain Various neuronal effects induced by elavl3, sox10, and mbp
1315	Increase, Selective Serotonin Reuptake Inhibitors (SSRIs)	Molecular	Apr 13, 2017	Apr 13, 2017
2049	Increase, sex ratio (F/M)	Individual	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
872	Increase, Site of Contact Nasal Tumors	Organ	Nov 29, 2016	Sep 16, 2017	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors Cytochrome oxidase inhibition leading to olfactory nasal lesions
2021	Increase, slincR expression	Molecular	Jun 29, 2022	Aug 1, 2022	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity
1525	Increase, Sulfonylurea receptor binding	Molecular	May 24, 2018	May 24, 2018	S-adenosylmethionine depletion leading to population decline (2) Sulfonylureareceptor binding leading to mortality
1381	Increase, surfactant	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1748	Increase, the risk of acute respiratory failure	Organ	Mar 10, 2020	Mar 10, 2020	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
753	Increase, Thyroid-stimulating hormone (TSH)	Tissue	Nov 29, 2016	Sep 16, 2017
868	Increase, Tissue Degeneration, Necrosis & Atrophy	Tissue	Nov 29, 2016	Sep 16, 2017	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors
1809	Increase, Tissue/organ damage	Organ	Nov 2, 2020	Nov 2, 2020	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
1950	Increase, TNF	Molecular	Nov 18, 2021	Nov 18, 2021	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)
1471	Increase, Uncoupling of photophosphorylation	Cellular	Oct 10, 2017	Oct 10, 2017	Reduction in photophosphorylation leading to growth inhibition in aquatic plants
793	Increase, Urinary bladder calculi	Organ	Nov 29, 2016	Oct 26, 2017	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)
2161	Increase, Vascular disrupting effects	Individual	Aug 19, 2023	Aug 19, 2023	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction Demethylation of PPAR promotor leading to vascular disrupting effects The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
1342	Increase, vascular smooth muscle contraction	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) SSRI (Selective serotonin reuptake inhibitor) to hypertension
2046	Increase, Vitellogenin mRNA	Molecular	Aug 28, 2022	Aug 28, 2022	Alcohol dehydrogenase leading to reproductive dysfunction
307	Increase, Vitellogenin synthesis in liver	Tissue	Nov 29, 2016	Jun 24, 2024	Estrogen receptor agonism leading to reproductive dysfunction Estrogen receptor agonism leading to reduced survival and population growth due to renal failure Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
1745	Increase,collagen synthesis	Cellular	Mar 10, 2020	Mar 10, 2020
1888	Increased (ectopic) all-trans retinoic acid concentration	Tissue	May 29, 2021	Nov 11, 2021	Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
1948	Increased ACE2 expression	Molecular	Oct 28, 2021	Oct 28, 2021	SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
1172	Increased activation, Nuclear factor kappa B (NF-kB)	Cellular	Nov 29, 2016	Aug 27, 2023	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Binding to ACE2 leading to lung fibrosis DNA damage and mutations leading to Metastatic Breast Cancer
1039	Increased activity, beta-2 adrenergic receptor	Molecular	Nov 29, 2016	Sep 16, 2017	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
2128	Increased adipocyte numbers	Cellular	Apr 5, 2023	Apr 5, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
2127	Increased adipocyte size	Cellular	Apr 5, 2023	Apr 5, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
1449	increased adipogenesis	Tissue	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
1852	Increased Ang II type 1 receptor (AT1R)	Tissue	Mar 30, 2021	Mar 30, 2021	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
1752	Increased Angiotensin II	Cellular	Mar 17, 2020	Apr 4, 2021	Binding to ACE2 leading to lung fibrosis Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation Binding of viral S-glycoprotein to ACE2 receptor leading to dysgeusia
1026	Increased Apoptosis, Adenomas/carcinomas (follicular cell)	Tissue	Nov 29, 2016	Sep 16, 2017
496	Increased apoptosis, decreased fetal/adult Leydig Cells	Cellular	Nov 29, 2016	May 17, 2023	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1722	Increased blood CCK level	Organ	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
1663	Increased brain Homocysteine level	Organ	Jun 14, 2019	Jun 14, 2019
1433	Increased CGRP, neuronal release of CGRP	Cellular	Jun 23, 2017	Sep 16, 2017	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
39	Increased Cholinergic Signaling	Organ	Nov 29, 2016	Dec 20, 2019	Acetylcholinesterase inhibition leading to acute mortality Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function
1723	Increased exocrine secretion from pancreatic acinar cells	Cellular	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
2125	Increased fat mass	Organ	Apr 5, 2023	Apr 5, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
1661	Increased Homocysteine level	Cellular	Jun 14, 2019	Jun 14, 2019	Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
2235	Increased incidence and mortality of liver diseases among children	Population	Jun 26, 2024	Jun 26, 2024
1929	Increased incidence of cardiovascular morbidity and mortality in the general population	Population	Aug 21, 2021	Aug 21, 2021
2247	Increased incidence of cerebrovascular morbidility and mortality in the general population	Population	Jul 29, 2024	Jul 29, 2024
1996	Increased incidence of digestive morbidity and mortality in the general population	Population	Apr 7, 2022	Apr 7, 2022
2087	Increased incidence of respiratory disease	Individual	Jan 9, 2023	Jan 9, 2023	AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1992	Increased incidence of respiratory morbidity and mortality in the general population	Population	Apr 7, 2022	Apr 7, 2022
2183	Increased incidence of vascular calcification and atherosclerosis morbidity	Population	Sep 4, 2023	Nov 14, 2023
1750	Increased inflammatory immune responses	Tissue	Mar 10, 2020	Jan 21, 2021	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
1721	Increased intestinal monitor peptide level	Organ	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
2149	Increased intracelluar Iron accumulation	Cellular	Jun 15, 2023	Jun 15, 2023	Increased LCN2/iron complex leading to neurological disorders Excessive iron accumulation leading to neurological disorders
2148	Increased LCN2/iron complex binds to SLC22A17 receptor in neuron	Molecular	Jun 15, 2023	Jun 15, 2023	Increased LCN2/iron complex leading to neurological disorders
2130	increased lipid accumulation	Cellular	Apr 5, 2023	Apr 5, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
1256	increased mantel display	Organ	Jan 13, 2017	Jan 13, 2017	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
1980	Increased microRNA expression	Cellular	Mar 22, 2022	Aug 27, 2023	DNA damage and mutations leading to Metastatic Breast Cancer
2081	Increased Modified Proteins	Molecular	Dec 16, 2022	Mar 8, 2024	Deposition of energy leading to occurrence of cataracts
2156	Increased morbidity of congenital heart defect	Population	Jul 31, 2023	Jul 31, 2023
351	Increased Mortality	Population	Nov 29, 2016	Jul 8, 2022	Acetylcholinesterase inhibition leading to acute mortality Axonal sodium channel modulation leading to acute mortality Altered ion channel activity leading impaired heart function Glutamate-gated chloride channel activation leading to acute mortality Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality unknown MIE leading to renal failure and mortality Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure GSK3beta inactivation leading to increased mortality via defects in developing inner ear Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality Estrogen receptor agonism leading to reduced survival and population growth due to renal failure
1999	Increased mortality of neurodegenerative diseases	Population	Apr 7, 2022	Apr 7, 2022
1897	increased MyD88 activation	Molecular	Jul 8, 2021	Jul 8, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
1435	Increased neurokinin A (NKA) by neuronal cells	Cellular	Jun 23, 2017	Sep 16, 2017	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1147	increased or inappropriate, mantel display	Individual	Nov 29, 2016	Dec 3, 2016
1662	Increased plasma Homocysteine level	Tissue	Jun 14, 2019	Jun 14, 2019
1900	increased platelet surface TLR9 expression	Cellular	Jul 8, 2021	Jul 8, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
2132	Increased pro-inflammatory cytokine expression	Cellular	Apr 6, 2023	Apr 6, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
1493	Increased Pro-inflammatory mediators	Tissue	Nov 28, 2017	Sep 17, 2024	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 Protein Alkylation leading to Liver Fibrosis Endocytic lysosomal uptake leading to liver fibrosis Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia Deposition of energy leads to abnormal vascular remodeling
1546	Increased reactive oxygen species (in the mitochondria)	Cellular	Dec 19, 2018	Dec 19, 2018	Mitochondrial complex inhibition leading to liver injury
1898	increased release of danger/damage associated molecular patterns	Tissue	Jul 8, 2021	Jul 8, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
1226	Increased Respiratory irritability and Chronic Cough,	Organ	Nov 29, 2016	Sep 24, 2018	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1847	Increased SARS-CoV-2 production	Cellular	Mar 25, 2021	Jun 14, 2022	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality SARS-CoV-2 infection leading to hyperinflammation SARS-CoV-2 infection leading to pyroptosis Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia) Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
1855	Increased Sodium-sensitive hypertension	Tissue	Apr 7, 2021	Apr 7, 2021	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease
2033	Increased sphingolipid-1-phosphate	Cellular	Jul 19, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
2248	Increased stress hormone	Cellular	Jul 29, 2024	Jul 29, 2024
1460	Increased Substance P (SP) by goblet cells	Cellular	Jul 27, 2017	Jul 27, 2017
2246	Increased sympathetic nerve activity	Cellular	Jul 29, 2024	Jul 29, 2024
1441	Increased systemic total cholesterol pool	Organ	Jun 29, 2017	Jun 29, 2017
1858	Increased viral transcription and replication	Cellular	Apr 9, 2021	Apr 9, 2021
1030	Increased,		Nov 29, 2016	Nov 29, 2016
1326	Increased, 5-HT3 (5-hydroxytryptamine)	Molecular	Apr 13, 2017	Jun 1, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
708	Increased, Accumulation of alpha2u microglobulin (proximal tubular epithelium)	Tissue	Nov 29, 2016	Sep 16, 2017	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
134	Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells)	Cellular	Nov 29, 2016	Sep 16, 2017
1499	Increased, activation of T (T) helper (h) type 2 cells	Tissue	Jan 3, 2018	May 12, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
1082	Increased, adenomas (pituitary)	Tissue	Nov 29, 2016	Sep 16, 2017	GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
1079	Increased, Adenomas/carcinomas (mammary)	Tissue	Nov 29, 2016	Sep 16, 2017	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
1070	Increased, adenosquamous carcinomas of endometrium	Tissue	Nov 29, 2016	Sep 16, 2017	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
1029	Increased, adipogenesis	Cellular	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters
1345	Increased, agitation	Molecular	Apr 13, 2017	Jun 1, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to agitation Serotonin transporter activation to agitation
591	Increased, amputations	Individual	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to congenital malformations
1213	Increased, Angiogenesis	Cellular	Nov 29, 2016	Dec 20, 2022	Estrogen receptor activation leading to breast cancer
880	Increased, ApoB100	Tissue	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
574	Increased, Appetite and hunger	Individual	Nov 29, 2016	Dec 3, 2016	Increased metabolic stress contributes to abnormal foraging and leads to colony loss/failure
602	Increased, Ataxia, paralysis, or hyperactivity	Organ	Nov 29, 2016	Sep 16, 2017	Axonal sodium channel modulation leading to acute mortality
444	Increased, Atrioventricular block and bradycardia	Organ	Nov 29, 2016	Sep 16, 2017	Sodium channel inhibition leading to congenital malformations
2124	increased, Bax expression	Molecular	Apr 4, 2023	Sep 7, 2023	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
714	Increased, Binding of chemicals to 2u (serum)	Molecular	Nov 29, 2016	Sep 16, 2017	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)
1098	Increased, blood potassium concentration	Tissue	Nov 29, 2016	Sep 16, 2017	Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality unknown MIE leading to renal failure and mortality
1096	Increased, blood uric acid concentration	Tissue	Nov 29, 2016	Sep 16, 2017	Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
2238	Increased, Blood viscosity	Tissue	Jul 8, 2024	Sep 26, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
699	Increased, cardiac arrthymia	Organ	Nov 29, 2016	Sep 16, 2017	Altered ion channel activity leading impaired heart function
2239	Increased, Cardiac stress	Organ	Jul 8, 2024	Sep 27, 2024	Decreased Sodium/Potassium ATPase activity leads to Heart failure
863	Increased, Catabolism of Muscle Protein	Organ	Nov 29, 2016	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
1089	Increased, Cell Proliferation (mesothelium)	Cellular	Nov 29, 2016	Sep 16, 2017	Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
1062	Increased, Cellular proliferation / hyperplasia of acinar cells	Cellular	Nov 29, 2016	Sep 16, 2017	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
761	Increased, Chloride conductance	Cellular	Nov 29, 2016	Sep 16, 2017	Glutamate-gated chloride channel activation leading to acute mortality Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
1011	Increased, Chloride influx		Nov 29, 2016	Nov 29, 2016
1059	Increased, cholestasis	Organ	Nov 29, 2016	Sep 16, 2017	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
696	Increased, Chromosome misseggregation	Cellular	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
1162	Increased, cilia movement	Cellular	Nov 29, 2016	Dec 3, 2016
1076	Increased, circulating estrogen levels	Organ	Nov 29, 2016	Dec 3, 2016	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat. Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
961	Increased, Clearance of thyroxine from serum	Tissue	Nov 29, 2016	Jan 26, 2021	Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
384	Increased, Clonal Expansion / Cell Proliferatin to form Pre-Neoplastic Altered Hepatic Foci		Nov 29, 2016	Nov 29, 2016
423	Increased, Clonal Expansion / Cell Proliferation to Form Pre-Neoplastic Altered Hepatic Foci		Nov 29, 2016	Nov 29, 2016
693	Increased, cyclic adenosine monophosphate	Tissue	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
458	Increased, De Novo FA synthesis	Cellular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis NFE2L2/FXR activation leading to hepatic steatosis
1109	Increased, Deformed Wing Virus levels	Individual	Nov 29, 2016	Dec 3, 2016	Varroa mite infestation increases virus levels leading to colony loss/failure
1346	Increased, depression	Individual	Apr 13, 2017	Jun 1, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Serotonin transporter activation to depression
1001	Increased, Developmental Defects	Molecular	Nov 29, 2016	Aug 31, 2023	Disruption of VEGFR Signaling Leading to Developmental Defects
1790	Increased, Differentiation to Testis	Tissue	Jun 15, 2020	Dec 28, 2022	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation Androgen receptor agonism leading to male-biased sex ratio
323	Increased, Disease susceptibility	Individual	Nov 29, 2016	Dec 3, 2016	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
1669	Increased, DNA damage and mutation	Cellular	Jul 3, 2019	Aug 13, 2019	Frustrated phagocytosis-induced lung cancer Frustrated phagocytosis leads to malignant mesothelioma Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway DNA damage and mutations leading to Metastatic Breast Cancer Interaction with lung resident cell membrane components leads to lung cancer
1281	Increased, DNA Damage-Repair	Cellular	Feb 15, 2017	Sep 16, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans
1192	Increased, Ductal Hyperplasia	Tissue	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
1110	Increased, Energetic demands and therefore metabolic stress	Individual	Nov 29, 2016	Dec 3, 2016	Nosema infection increases energetic demands leading to colony loss/failure
1363	Increased, epilepsy	Individual	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy presynaptic neuron 2 repression to epilepsy Various neuronal effects induced by elavl3, sox10, and mbp
1187	Increased, ER binding to DNA (classical pathway)	Molecular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
1188	Increased, ER binding to T.F. to DNA (non-classical pathway)	Molecular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
2205	Increased, essential element imbalance	Molecular	Jan 24, 2024	May 9, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
748	Increased, Estrogen receptor (ER) activity	Molecular	Nov 29, 2016	Dec 3, 2016	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat) Alcohol dehydrogenase leading to reproductive dysfunction
1973	Increased, estrogens	Cellular	Feb 25, 2022	Mar 1, 2022	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
2199	Increased, Expression of LXR activated genes	Molecular	Dec 7, 2023	Mar 29, 2024	Liver X Receptor (LXR) activation leads to liver steatosis
1501	Increased, extracellular matrix deposition	Tissue	Jan 5, 2018	Jan 25, 2022	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway AhR activation leading to liver fibrosis
1320	Increased, extracellular serotonin	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation Serotonin transporter activation to seizure Serotonin transporter activation to depression Serotonin transporter activation to agitation SSRI (Selective serotonin reuptake inhibitor) to hypertension
465	Increased, FA Influx	Cellular	Nov 29, 2016	Sep 16, 2017	AhR activation leading to hepatic steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis
460	Increased, Fatty acid uptake	Cellular	Nov 29, 2016	Dec 3, 2016
1500	Increased, fibroblast proliferation and myofibroblast differentiation	Tissue	Jan 5, 2018	May 17, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis
1035	Increased, Firbrosarcoma	Tissue	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters
624	Increased, foot detachment	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
959	Increased, Free serum thyroxine (T4)	Tissue	Nov 29, 2016	Sep 16, 2017	Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis
2143	Increased, gene expression of AR	Molecular	May 18, 2023	May 18, 2023	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
421	Increased, glomerular rupture and renal hemorrhaging	Organ	Nov 29, 2016	Sep 16, 2017	ER agonism leading to reduced survival due to renal failure
1396	Increased, glucocorticoid receptor activity	Molecular	May 31, 2017	May 31, 2017	Mental stress to depression Mental stress to agitation
1350	Increased, glutamate	Molecular	Apr 14, 2017	Oct 11, 2021	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy Acetylcholinesterase Inhibition Leading to Neurodegeneration Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
2079	Increased, glycolipid levels	Cellular	Dec 13, 2022	May 17, 2023	Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
1037	Increased, hemagiosarcoma	Tissue	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters
1158	Increased, Hepatic thyroid hormone uptake/transport	Tissue	Nov 29, 2016	Sep 16, 2017	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
802	Increased, HIF-1 alpha transcription	Cellular	Nov 29, 2016	Dec 3, 2016	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
799	Increased, HIF-1 heterodimer	Cellular	Nov 29, 2016	Dec 3, 2016	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
1362	Increased, hippocampal hyperdepolarization	Molecular	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy presynaptic neuron 2 repression to epilepsy
2206	Increased, histomorphological alteration of testis	Tissue	Jan 24, 2024	Apr 10, 2024	Essential element imbalance leads to reproductive failure via oxidative stress
1025	Increased, Hyperplasia (follicular cells)	Tissue	Nov 29, 2016	Sep 16, 2017
1069	Increased, Hyperplasia (glandular epithelial cells of endometrium)	Cellular	Nov 29, 2016	Sep 16, 2017	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
1085	Increased, hyperplasia (mammary gland)	Tissue	Nov 29, 2016	Sep 16, 2017	Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
1024	Increased, Hypertrophy and proliferation (follicular cell)	Cellular	Nov 29, 2016	Sep 16, 2017
1034	Increased, IGF-1 (mouse)	Cellular	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters
376	Increased, Induced Mutations in Critical Genes	Cellular	Nov 29, 2016	Sep 16, 2017	AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
726	Increased, Induction of pyruvate dehydrogenase (PDH)	Molecular	Nov 29, 2016	Dec 3, 2016	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
1020	Increased, induction of UDPGT's in liver	Cellular	Nov 29, 2016	Sep 16, 2017
1087	Increased, inflammation	Cellular	Nov 29, 2016	Dec 3, 2016	Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
1012	Increased, Inhibitory postsynaptic potential	Cellular	Nov 29, 2016	Sep 16, 2017	Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality Various neuronal effects induced by elavl3, sox10, and mbp
493	Increased, Insufficient repair or mis-repair of pro-mutagenic DNA adducts	Molecular	Nov 29, 2016	Sep 16, 2017	AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
1933	Increased, Interleukin-6 production	Cellular	Sep 20, 2021	Sep 20, 2021	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway
389	Increased, Intracellular Calcium overload	Cellular	Nov 29, 2016	Jun 26, 2020	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Acetylcholinesterase Inhibition Leading to Neurodegeneration Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons Binding and activation of GPER leading to learning and memory impairments
1322	Increased, intracellular chloride (Cl-)	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Molecular events lead to epilepsy
1398	Increased, intracellular serotonin	Cellular	Jun 1, 2017	Jun 1, 2017	Serotonin transporter activation to seizure Serotonin transporter activation to depression Serotonin transporter activation to agitation
1321	Increased, intracellular sodium (Na+)	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy
1196	Increased, Invasion	Cellular	Nov 29, 2016	Feb 29, 2024	Estrogen receptor activation leading to breast cancer Activation of the AhR leading to metastatic breast cancer Androgen receptor activation leading to prostate cancer
759	Increased, Kidney Failure	Population	Nov 29, 2016	Jan 16, 2019	Kidney toxicity induced by activation of 5HT2C Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
1985	Increased, Kisspeptin signalling	Molecular	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
1081	Increased, lactotroph hyperplasia and hypertrophy	Cellular	Nov 29, 2016	Sep 16, 2017	GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
1080	Increased, latency period	Individual	Nov 29, 2016	Dec 3, 2016	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
467	Increased, LDL uptake	Cellular	Nov 29, 2016	Sep 16, 2017	AhR activation leading to hepatic steatosis
342	Increased, Lethality		Nov 29, 2016	Nov 29, 2016
1411	Increased, leukocyte activation	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS2 inactivation to gastric ulcer
1410	Increased, leukocyte adherence	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS2 inactivation to gastric ulcer
791	Increased, Leutinizing hormone (LH)	Tissue	Nov 29, 2016	Sep 16, 2017	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
1306	Increased, lipogenesis	Molecular	Apr 12, 2017	Apr 12, 2017
1036	Increased, liposarcoma	Tissue	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters
459	Increased, Liver Steatosis	Organ	Nov 29, 2016	May 21, 2024	NR1I3 (CAR) suppression leading to hepatic steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis NFE2L2/FXR activation leading to hepatic steatosis AKT2 activation leading to hepatic steatosis Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH) Inhibition of N-linked glycosylation leads to liver injury Glucocorticoid Receptor activation leading to hepatic steatosis Pregnane X Receptor (PXR) activation leads to liver steatosis Liver X Receptor (LXR) activation leads to liver steatosis Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis NFE2/Nrf2 repression to steatosis AhR activation leading to hepatic steatosis AhR activation leading to liver fibrosis
622	Increased, locomotion	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
754	Increased, Luteinizing hormone (LH)	Tissue	Nov 29, 2016	Sep 16, 2017	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)
1791	Increased, Male Biased Sex Ratio	Population	Jun 15, 2020	Jan 3, 2023	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation Androgen receptor agonism leading to male-biased sex ratio
1208	Increased, Male offspring	Population	Nov 29, 2016	Dec 3, 2016	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
1160	Increased, mantel display	Individual	Nov 29, 2016	Dec 3, 2016
1090	Increased, mesotheliomas	Tissue	Nov 29, 2016	Dec 3, 2016	Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat. Frustrated phagocytosis leads to malignant mesothelioma
1190	Increased, Migration (Endothelial Cells)	Cellular	Nov 29, 2016	Feb 29, 2024	Estrogen receptor activation leading to breast cancer Activation of the AhR leading to metastatic breast cancer
1241	Increased, Motility	Cellular	Nov 29, 2016	Feb 28, 2024	Estrogen receptor activation leading to breast cancer Activation of the AhR leading to metastatic breast cancer
625	Increased, muscular waves in foot	Organ	Nov 29, 2016	Sep 16, 2017	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
422	Increased, nephropathy	Individual	Nov 29, 2016	Dec 3, 2016	ER agonism leading to reduced survival due to renal failure
1015	Increased, Neuronal synaptic inhibition	Cellular	Nov 29, 2016	Sep 16, 2017	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality Various neuronal effects induced by elavl3, sox10, and mbp
1191	Increased, Non-genomic signaling	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
1491	Increased, Oncotic Necrosis	Tissue	Nov 14, 2017	Nov 27, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
1990	Increased, Oocyte Atresia	Tissue	Apr 5, 2022	Apr 5, 2022	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
1161	Increased, oocyte maturation	Organ	Nov 29, 2016	Jan 17, 2017	5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
356	Increased, Oxidative damage	Individual	Nov 29, 2016	Dec 3, 2016
1088	Increased, Oxidative Stress	Molecular	Nov 29, 2016	Feb 3, 2022	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress
1399	Increased, packaged serotonin	Cellular	Jun 1, 2017	Jun 1, 2017	Serotonin transporter activation to seizure Serotonin transporter activation to depression Serotonin transporter activation to agitation
1063	Increased, Pancreatic acinar tumors	Organ	Nov 29, 2016	Sep 16, 2017	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
1665	Increased, Plasma HCY level	Tissue	Jul 3, 2019	Jul 3, 2019	Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
775	Increased, Plasma tyrosine	Tissue	Nov 29, 2016	Sep 16, 2017	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
1164	Increased, Population	Population	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
1057	Increased, PPAR-alpha activation	Molecular	Nov 29, 2016	Sep 16, 2017	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
588	Increased, predation	Population	Nov 29, 2016	Dec 3, 2016	sodium channel inhibition leading to increased predation Sodium channel inhibition leading to reduced survival Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation Histamine (H2) receptor antagonism leading to reduced survival
1577	Increased, proinflammatory mediators (TNFalpha)	Molecular	Jan 7, 2019	Jan 7, 2019
1077	Increased, prolactin exposure	Tissue	Nov 29, 2016	Dec 3, 2016	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat.
1084	Increased, prolactin secretion	Tissue	Nov 29, 2016	Dec 3, 2016	Anti-dopaminergic activity leading to mammary adenomas and carcinomas in the SD rat
1189	Increased, Proliferation (Endothelial cells)	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
1033	Increased, proliferation of mesenchymal cells	Cellular	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters
377	Increased, Proliferation/Clonal Expansion of Mutant Cells (Pre-Neoplastic Lesions/Altered Hepatic Foci (AHF))		Nov 29, 2016	Nov 29, 2016
1357	Increased, RDX dose	Molecular	Apr 14, 2017	Jun 2, 2017	Molecular events lead to epilepsy presynaptic neuron 2 repression to epilepsy
1922	Increased, Reactive metabolites production	Cellular	Aug 19, 2021	Aug 26, 2021	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway
1115	Increased, Reactive oxygen species	Cellular	Nov 29, 2016	Apr 10, 2024	unknown MIE leading to renal failure and mortality Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH) Frustrated phagocytosis-induced lung cancer Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease Deposition of ionizing energy leads to population decline via impaired meiosis Frustrated phagocytosis leads to malignant mesothelioma Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway Deposition of ionizing energy leading to population decline via inhibition of photosynthesis Deposition of ionising energy leading to population decline via mitochondrial dysfunction Binding to ACE2 leading to lung fibrosis Interaction with lung resident cell membrane components leads to lung cancer Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity Glutathione conjugation leading to reproductive dysfunction via oxidative stress ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway Essential element imbalance leads to reproductive failure via oxidative stress Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
1497	Increased, recruitment of inflammatory cells	Tissue	Jan 3, 2018	May 12, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis Frustrated phagocytosis-induced lung cancer Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation Frustrated phagocytosis leads to malignant mesothelioma Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Interaction with lung resident cell membrane components leads to lung cancer Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death) ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
1031	Increased, release of growth factors		Nov 29, 2016	Nov 29, 2016
419	Increased, renal vitellogenin deposition	Organ	Nov 29, 2016	Sep 16, 2017	ER agonism leading to reduced survival due to renal failure
1163	Increased, Reproductive Success	Individual	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
1159	Increased, reuptake of 5-HT (5-hydroxytryptamine transporter; sodium-dependent serotonin transporter		Nov 29, 2016	Nov 29, 2016
1242	Increased, Second Messenger Production	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
1049	Increased, secrection of FSH from anterior pituitary	Cellular	Nov 29, 2016	Dec 3, 2016	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
2004	Increased, secretion of catecholamine	Cellular	Apr 22, 2022	Apr 22, 2022
1047	Increased, secretion of GnRH from hypothalamus	Cellular	Nov 29, 2016	Sep 16, 2017	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
1048	Increased, secretion of leutenizing hormone		Nov 29, 2016	Nov 29, 2016
1050	Increased, secretion of LH from anterior pituitary	Cellular	Nov 29, 2016	Dec 3, 2016	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
1032	Increased, secretion of local growth factors	Cellular	Nov 29, 2016	Sep 16, 2017	PPARgamma activation leading to sarcomas in rats, mice, and hamsters Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
1496	Increased, secretion of proinflammatory mediators	Cellular	Jan 2, 2018	May 17, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation Frustrated phagocytosis leads to malignant mesothelioma Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response Binding to ACE2 leading to lung fibrosis Interaction with lung resident cell membrane components leads to lung cancer Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death) Substance interaction with lung resident cell membrane components leading to atherosclerosis
1344	Increased, seizure	Individual	Apr 13, 2017	Jun 1, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Serotonin transporter activation to seizure presynaptic neuron 1 activation to epilepsy presynaptic neuron 2 repression to epilepsy
626	Increased, serotonin (5-HT)	Cellular	Nov 29, 2016	Sep 16, 2017	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline
620	Increased, serotonin (5-HT) 1 1	Molecular	Nov 29, 2016	Dec 3, 2016
1397	Increased, serotonin transporter activity	Cellular	Jun 1, 2017	Jun 1, 2017	Serotonin transporter activation to seizure Serotonin transporter activation to depression Serotonin transporter activation to agitation
813	Increased, Serum creatinine	Organ	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
2122	increased, socio-economic burden	Population	Apr 4, 2023	Feb 5, 2024
1972	Increased, Steroidogenic acute regulatory protein (StAR)	Cellular	Feb 25, 2022	Mar 1, 2022	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
366	Increased, Structural malformations		Nov 29, 2016	Nov 29, 2016
1400	Increased, synaptic release	Cellular	Jun 1, 2017	Jun 1, 2017	Serotonin transporter activation to seizure Serotonin transporter activation to depression Serotonin transporter activation to agitation
1021	Increased, T4/T3 catabolism	Cellular	Nov 29, 2016	Sep 16, 2017
1023	Increased, Thyroid-stimulating hormone (TSH)	Tissue	Nov 29, 2016	Sep 16, 2017	Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)
1828	Increased, Thyroxine (T4) in serum	Organ	Dec 9, 2020	Dec 9, 2020	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
881	Increased, Triglyceride	Cellular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
454	Increased, Triglyceride formation	Cellular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
1154	Increased, Triiodothyronine (T3) in tissues	Tissue	Nov 29, 2016	Dec 3, 2016	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
1971	Increased, tumor growth	Organ	Feb 15, 2022	Feb 29, 2024	Activation of the AhR leading to metastatic breast cancer
960	Increased, Uptake of thyroxine into tissue	Cellular	Nov 29, 2016	Dec 17, 2016	Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
1142	Increased, valve movement	Tissue	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
576	Increased, Viral susceptibility	Individual	Nov 29, 2016	Dec 3, 2016	Suppression of immune system contributes to impaired development and leads to colony loss/failure Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure
418	Increased, Vitellogenin synthesis	Cellular	Nov 29, 2016	Sep 16, 2017	ER agonism leading to reduced survival due to renal failure
1166	Increased, water pumping	Tissue	Nov 29, 2016	Dec 3, 2016
1139	Increased, water retention in foot	Organ	Nov 29, 2016	Dec 3, 2016	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline
1919	Increased，Cardiac Dysregulation	Tissue	Aug 18, 2021	Sep 1, 2021
1924	Increased，Cardiac fibrosis	Organ	Aug 19, 2021	Sep 1, 2021
1918	Increased，Myocardial apoptosis	Cellular	Aug 18, 2021	Sep 1, 2021
1926	Increased，Vascular fibrosis	Tissue	Aug 19, 2021	Sep 1, 2021
1927	Increased，Vascular endothelial cell autophagy dysfunction	Cellular	Aug 19, 2021	Sep 1, 2021
1928	increased，Vascular endothelial dysfunction	Tissue	Aug 19, 2021	Sep 1, 2021	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction Demethylation of PPAR promotor leading to vascular disrupting effects The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
1925	Increased，Vascular smooth muscle cell activation	Cellular	Aug 19, 2021	Sep 1, 2021
1940	Increases in cellular reactive oxygen species	Molecular	Oct 25, 2021	May 10, 2022	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
1455	Incudtion, Sustained inflammatory cytokine release	Molecular	Jul 26, 2017	Jul 26, 2017
1664	Induce Neuronal dysfunctions	Individual	Jun 14, 2019	Jun 14, 2019
1740	Induced dysregulation of ACE2	Molecular	Mar 10, 2020	Mar 3, 2022	Binding to ACE2 leading to lung fibrosis Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis
1257	Induced parturition	Individual	Jan 13, 2017	Jan 13, 2017	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
1255	induced spawning	Individual	Jan 13, 2017	Jan 13, 2017	5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase
1741	Induced, Angiotensin (Ang) II accumulation	Tissue	Mar 10, 2020	Mar 30, 2021	ACE2 downregulation following SARS-CoV-2 infection triggers dysregulation of RAAS and can lead to heart failure.
1666	Induced, dysfunction of microcirculation	Organ	Jul 3, 2019	Jul 3, 2019	Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
1167	induced, parturition	Individual	Nov 29, 2016	Dec 3, 2016
1746	Induction lung fibrosis	Organ	Mar 10, 2020	Mar 10, 2020
1711	Induction of GATA3 expression	Cellular	Dec 29, 2019	Aug 14, 2020	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)
1959	Induction of hERG trafficking defects	Cellular	Dec 13, 2021	Dec 13, 2021
1459	Induction, Cell damage sensing	Molecular	Jul 26, 2017	Jul 26, 2017
60	Induction, Chitin degradation and resorption		Nov 29, 2016	Nov 29, 2016
850	Induction, CYP1A2/CYP1A5	Molecular	Nov 29, 2016	May 30, 2018	Aryl hydrocarbon receptor activation leading to uroporphyria AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1206	Induction, Doublesex1 gene	Molecular	Nov 29, 2016	Sep 16, 2017	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
145	Induction, IKB inhibitory protein	Cellular	Nov 29, 2016	Sep 16, 2017	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
164	Induction, Liver “Dysfunctional” Changes by CGA 330050	Organ	Nov 29, 2016	Sep 16, 2017	Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
1209	Induction, Male reproductive tract	Organ	Nov 29, 2016	Sep 16, 2017	Juvenile hormone receptor agonism leading to male offspring induction associated population decline
1207	Induction, Male traits formation in embryos		Nov 29, 2016	Nov 29, 2016
838	Induction, Microvesicular fat	Tissue	Nov 29, 2016	Dec 3, 2016	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
1394	Induction, persistent proliferation/sustained proliferation	Cellular	May 30, 2017	Jun 19, 2021	Cyp2E1 Activation Leading to Liver Cancer
1019	Induction, pharyngeal muscle paralysis	Tissue	Nov 29, 2016	Sep 16, 2017	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality
238	Induction, Pre-mature molting		Nov 29, 2016	Nov 29, 2016
1014	Induction, Somatic muscle paralysis	Tissue	Nov 29, 2016	Sep 16, 2017	Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality Various neuronal effects induced by elavl3, sox10, and mbp
269	Induction, Sustained Cell Proliferation	Cellular	Nov 29, 2016	Sep 16, 2017	Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
270	Induction, Sustained Hepatotoxicity	Individual	Nov 29, 2016	Dec 3, 2016	Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
295	Induction, Upregulation of glucuronyltransferase activity	Molecular	Nov 29, 2016	Sep 16, 2017	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Hepatic nuclear receptor activation leading to altered amphibian metamorphosis Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1254	Infant leukaemia	Individual	Dec 16, 2016	Aug 1, 2022	Inhibitor binding to topoisomerase II leading to infant leukaemia
901	Infiltration, Inflammatory cells	Tissue	Nov 29, 2016	Sep 16, 2017
907	Infiltration, Inflammatory cytokines		Nov 29, 2016	Nov 29, 2016
1599	Inflamatory events in light-exposed tissues	Organ	Feb 3, 2019	Jul 4, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure Androgen receptor activation leading to prostate cancer
902	Inflammation, Liver	Organ	Nov 29, 2016	Sep 16, 2017	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
2158	Influenza A Virus (IAV) binds sialic acid glycan receptor	Molecular	Jul 31, 2023	Aug 2, 2023	Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
2193	Influenza A Virus (IAV) budding	Cellular	Oct 2, 2023	Jan 29, 2024	Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
2159	Influenza A virus (IAV) cell entry	Cellular	Aug 11, 2023	Oct 3, 2023	Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
2194	Influenza A Virus (IAV) shedding and transmission	Individual	Oct 2, 2023	Oct 2, 2023	Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
2192	Influenza A Virus production increased	Molecular	Oct 2, 2023	Jan 29, 2024	Binding of Influenza A Virus (IAV) to Sialic Acid Glycan Receptor leads to viral infection proliferation
1216	Influx of Ca2+, Excitation of trigeminal nerves		Nov 29, 2016	Nov 29, 2016
1470	inherited mutations in offspring	Individual	Aug 20, 2017	Aug 20, 2017
1331	Inhibit, agitation	Individual	Apr 13, 2017	Apr 13, 2017
1332	Inhibit, depression	Individual	Apr 13, 2017	Apr 13, 2017
1367	Inhibit, gastric ulcer formation	Organ	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1316	Inhibit, serotonin transporter activity	Molecular	Apr 13, 2017	Apr 13, 2017	Network of SSRIs (selective serotonin reuptake inhibitors)
2039	Inhibition GABAA receptor	Molecular	Jul 25, 2022	Jul 25, 2022	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
1799	Inhibition of 11β-HSD	Molecular	Jul 13, 2020	Jul 13, 2020	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory
1880	Inhibition of ALDH1A (RALDH)	Molecular	May 24, 2021	Nov 11, 2021	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
59	Inhibition of Apoptosis in Altered Hepatic Foci, Changes in Cellular Growth Homeostasis		Nov 29, 2016	Nov 29, 2016
964	Inhibition of Aromatase Enzyme, Chemical exposure during critical window of estrous cycle between diestrus 2 and proestrus inhibits aromatase conversion of testosterone to estradiol	Molecular	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
1660	Inhibition of betaine-homocysteine methyltransferase	Molecular	Jun 14, 2019	Jun 14, 2019
2023	Inhibition of Ceramide Synthase	Molecular	Jul 14, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
1887	Inhibition of CYP26B1 activity	Molecular	May 28, 2021	Nov 11, 2021
1657	Inhibition of cystathionine beta-synthase	Molecular	Jun 14, 2019	Jun 14, 2019	Inhibition of Cystathionine Beta synthase leading to impaired the early development of anterior-posterior axis
1884	Inhibition of Fyna	Molecular	May 28, 2021	Dec 12, 2021	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
1960	Inhibition of Ikr	Tissue	Dec 13, 2021	Dec 13, 2021
1715	Inhibition of JAK3	Molecular	Jan 5, 2020	Feb 15, 2021	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
1672	Inhibition of lung surfactant function	Molecular	Jul 3, 2019	Oct 27, 2021	Lung surfactant function inhibition leading to decreased lung function
1463	Inhibition of lysyl oxidase	Cellular	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1658	Inhibition of Methionine synthase	Molecular	Jun 14, 2019	Jun 14, 2019
1659	Inhibition of Methylenetetrahydrofolate reductase	Molecular	Jun 14, 2019	Jun 14, 2019
1481	Inhibition of mitochondrial DNA polymerase gamma (Pol gamma)	Molecular	Oct 25, 2017	Oct 25, 2017	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity
1604	Inhibition of N-linked glycosylation	Molecular	Mar 6, 2019	Mar 6, 2019	Inhibition of N-linked glycosylation leads to liver injury
1429	Inhibition of N-type Ca ion channels	Cellular	Jun 23, 2017	Jun 23, 2017	Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
1430	Inhibition of neurotransmitter vesicle release	Cellular	Jun 23, 2017	Jun 27, 2023	Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
1885	Inhibition of Plxna2	Molecular	May 28, 2021	Oct 7, 2021	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
2100	Inhibition of rapid delayed rectifying potassium current	Cellular	Jan 29, 2023	Jan 29, 2023	hERG channel blockade leading to sudden cardiac death
2155	Inhibition of Sulfotransferase E1 (SULT1E1)	Molecular	Jul 28, 2023	Aug 14, 2023	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
2191	Inhibition of the Wnt/β-catenin pathway	Cellular	Sep 18, 2023	Sep 18, 2023
1627	Inhibition of tyrosinase	Molecular	May 3, 2019	May 3, 2019	Inhibition of tyrosinase leads to decreased population in fish
2174	Inhibition VEGF/VEGFR pathway	Cellular	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
766	Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme	Molecular	Nov 29, 2016	Dec 3, 2016	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)
619	Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)	Molecular	Nov 29, 2016	Sep 16, 2017	5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline 5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predation 5-hydroxytryptamine transporter (5-HTT) inhibition leading to population increase 5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline 5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase
1617	Inhibition, 5α-reductase	Molecular	Apr 18, 2019	Apr 5, 2024	Inhibition of 5α-reductase leading to impaired fecundity in female fish 5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring
790	Inhibition, 5α-reductase activity	Cellular	Nov 29, 2016	Dec 3, 2016	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)
1760	Inhibition, Activin signaling	Cellular	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
849	Inhibition, Antgonism of NE receptor	Molecular	Nov 29, 2016	Dec 3, 2016	Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation
36	Inhibition, Aromatase	Molecular	Nov 29, 2016	Mar 14, 2022	Aromatase inhibition leading to reproductive dysfunction Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
41	Inhibition, Bile Salt Export Pump (ABCB11)	Molecular	Nov 29, 2016	Sep 16, 2017	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
51	Inhibition, Ca++ ATPase	Molecular	Nov 29, 2016	Sep 16, 2017	Calcium-mediated neuronal ROS production and energy imbalance
980	Inhibition, Calcineurin Activity	Molecular	Nov 29, 2016	Jun 27, 2021	Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
1522	Inhibition, Chitin synthase 1	Molecular	May 24, 2018	Feb 24, 2021	S-adenosylmethionine depletion leading to population decline (1) Chitin synthase 1 inhibition leading to mortality
1806	Inhibition, Chitinase	Molecular	Oct 21, 2020	Sep 8, 2021	Chitinase inhibition leading to mortality
1807	Inhibition, Chitobiase	Molecular	Oct 21, 2020	Sep 8, 2021	Chitobiase inhibition leading to mortality
1103	Inhibition, Cyclooxygenase 1 activity	Molecular	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
79	Inhibition, Cyclooxygenase activity	Molecular	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading reproductive failure Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint Cyclooxygenase inhibition leading to reproductive dysfunction Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
1840	Inhibition, cytochrome oxidase	Molecular	Feb 19, 2021	Feb 19, 2021	Cytochrome oxidase inhibition leading to olfactory nasal lesions
1609	Inhibition, Cytochrome P450 enzyme (CYP17A1) activity	Molecular	Apr 10, 2019	Apr 10, 2019	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
1009	Inhibition, Deiodinase 1	Molecular	Nov 29, 2016	Oct 10, 2022	Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis
1002	Inhibition, Deiodinase 2	Molecular	Nov 29, 2016	Oct 7, 2022	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis
1153	Inhibition, Deiodinase 3	Molecular	Nov 29, 2016	Dec 3, 2016	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis
1156	Inhibition, Dual oxidase	Molecular	Nov 29, 2016	Dec 3, 2016	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis
2207	inhibition, EKR1/2 signaling pathway	Cellular	Jan 25, 2024	Jan 25, 2024	Estrogen antagonism leading to increased risk of autism-like behavior
593	Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel	Molecular	Nov 29, 2016	Dec 3, 2016	Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
1490	Inhibition, Fatty Acid Beta Oxidation	Molecular	Nov 13, 2017	Nov 27, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)
2065	Inhibition, Fatty acid oxidation	Cellular	Sep 19, 2022	Sep 28, 2022	PM2.5-related AOP frameworks on liver diseases
1016	Inhibition, Feeding	Individual	Nov 29, 2016	Dec 3, 2016	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality Various neuronal effects induced by elavl3, sox10, and mbp
1761	Inhibition, Fin regeneration	Tissue	Apr 21, 2020	Jul 10, 2020	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
471	Inhibition, FoxA2	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis
804	Inhibition, HMG-CoA reductase	Cellular	Nov 29, 2016	Dec 3, 2016	HMG-CoA reductase inhibition leading to decreased fertility
1574	Inhibition, IKK complex	Molecular	Jan 7, 2019	Jan 7, 2019	IKK complex inhibition leading to liver injury
147	Inhibition, Inducible Nitric Oxide Synthase by Metabolite CGA 265307	Cellular	Nov 29, 2016	Sep 16, 2017	Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
526	Inhibition, Inhibition of Dopamine-beta-hydroxylase	Molecular	Nov 29, 2016	Sep 16, 2017	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity
1152	Inhibition, Iodotyrosine deiodinase (IYD)	Molecular	Nov 29, 2016	Sep 16, 2017	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis
1308	Inhibition, LRH-1	Molecular	Apr 12, 2017	Apr 12, 2017
1307	Inhibition, LXR	Molecular	Apr 12, 2017	Apr 12, 2017
105	Inhibition, Mitochondrial Electron Transport Chain Complexes	Molecular	Nov 29, 2016	Mar 22, 2023	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress Mitochondrial complexes inhibition leading to heart failure via decreased ATP production
451	Inhibition, Mitochondrial fatty acid beta-oxidation	Molecular	Nov 29, 2016	Sep 16, 2017	AhR activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis NFE2L2/FXR activation leading to hepatic steatosis
2258	Inhibition, monocarboxylate transporter 8 (MCT8)	Molecular	Aug 28, 2024	Aug 28, 2024
1013	Inhibition, Motor neuron activity		Nov 29, 2016	Nov 29, 2016
424	Inhibition, Na+/I- symporter (NIS)	Molecular	Nov 29, 2016	Apr 4, 2019	XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)
887	Inhibition, NADH-ubiquinone oxidoreductase (complex I)	Cellular	Nov 29, 2016	Mar 12, 2018	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome Mitochondrial complex inhibition leading to liver injury
195	Inhibition, NMDARs	Molecular	Nov 29, 2016	Sep 16, 2017	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 Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Estrogen antagonism leading to increased risk of autism-like behavior
202	Inhibition, Nuclear factor kappa B (NF-kB)	Molecular	Nov 29, 2016	Mar 2, 2023	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility IKK complex inhibition leading to liver injury Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
877	Inhibition, organic anion transporter 1 (OAT1)	Molecular	Nov 29, 2016	Sep 16, 2017	Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
1155	Inhibition, Pendrin	Molecular	Nov 29, 2016	Dec 3, 2016	Pendrin inhibition leading to altered amphibian metamorphosis
828	Inhibition, Phospholipase A	Molecular	Nov 29, 2016	Dec 3, 2016	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
468	Inhibition, PPAR alpha	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis
798	Inhibition, Prolyl hydroxylases	Cellular	Nov 29, 2016	Dec 3, 2016	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Succinate dehydrogenase inactivation leading to cancer
1368	Inhibition, PTGS-1 (Prostaglandin-endoperoxide synthase 1)	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
1371	Inhibition, PTGS-2 (Prostaglandin-endoperoxide synthase 2)	Molecular	Apr 17, 2017	Apr 17, 2017	Gastric ulcer formation
724	Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme	Cellular	Nov 29, 2016	Dec 3, 2016	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
584	Inhibition, sodium channel	Molecular	Nov 29, 2016	Sep 16, 2017	Sodium channel inhibition leading to reduced survival sodium channel inhibition leading to increased predation Sodium channel inhibition leading to congenital malformations Sodium channel (Nav1.1) inhibition leading to population decline
878	Inhibition, SREBP1c	Molecular	Nov 29, 2016	Sep 16, 2017	NFE2L2/FXR activation leading to hepatic steatosis
1680	Inhibition, TBX1	Molecular	Aug 13, 2019	Aug 13, 2019	TBX1 inhibition leading to congenital cardiac conotruncal anomalies
845	Inhibition, UROD	Molecular	Nov 29, 2016	May 30, 2018	Aryl hydrocarbon receptor activation leading to uroporphyria
305	Inhibition, VegfR2	Molecular	Nov 29, 2016	Jan 17, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects
1294	Inhibition, Wnt pathway	Cellular	Feb 15, 2017	Sep 16, 2017	Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
2255	Innate immune response, activation	Cellular	Aug 13, 2024	Sep 13, 2024	Gluten intake leading to celiac disease - under development
2037	Inositol triphosphate receptor activation	Molecular	Jul 25, 2022	Jul 25, 2022	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
298	Insufficiency, Vascular	Molecular	Nov 29, 2016	Jul 20, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects
2119	Insulin resistance, increased	Individual	Apr 3, 2023	May 26, 2023	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine PM2.5-related AOP frameworks on liver diseases ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
1584	Interaction of α-diketones with arginine residues	Molecular	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans
979	Interference, nuclear localization of NFAT	Molecular	Nov 29, 2016	Jul 2, 2021	Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
1901	Interferon-I antiviral response, antagonized by SARS-CoV-2	Cellular	Jul 9, 2021	Dec 15, 2023	Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
1074	interruption, Ovulation	Individual	Nov 29, 2016	Dec 3, 2016	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
1931	Intestinal barrier, disruption	Organ	Sep 1, 2021	Jun 21, 2022	Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption Endocytotic lysosomal uptake leads to intestinal barrier disruption Gluten intake leading to celiac disease - under development
2014	Intestinal epithelial cell apoptosis	Cellular	Jun 6, 2022	Jun 7, 2022
2015	Intestinal inflammation	Organ	Jun 6, 2022	Jun 6, 2022
405	irregularities, ovarian cycle	Individual	Nov 29, 2016	Nov 29, 2016	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary Androgen receptor (AR) antagonism leading to decreased fertility in females
1134	Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone	Molecular	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1117	Irreversible inhibition of VKOR by binding at tyrosine 139,		Nov 29, 2016	Nov 29, 2016
1118	Irreversible inhibition of VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone		Nov 29, 2016	Nov 29, 2016
1434	Irritation of nasal mucosa inducing sneeze reflex	Tissue	Jun 23, 2017	Sep 16, 2017	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
927	KE1 : S-Glutathionylation, eNOS	Molecular	Nov 29, 2016	Nov 20, 2017	Peptide Oxidation Leading to Hypertension
935	KE2 : Decrease, GTPCH-1	Cellular	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension
934	KE3 : Decrease, Tetrahydrobiopterin	Cellular	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension
932	KE4 : Uncoupling, eNOS	Cellular	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
973	KE5 : Decrease, AKT/eNOS activity	Cellular	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension
933	KE6 : Depletion, Nitric Oxide	Cellular	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension
937	KE7 : Impaired, Vasodilation	Organ	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension
951	KE8 : Increase, Vascular Resistance	Organ	Nov 29, 2016	Nov 9, 2017	Peptide Oxidation Leading to Hypertension
1795	Latent Transforming growth Factor beta expression	Cellular	Jul 9, 2020	Jul 9, 2020	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1494	Leukocyte recruitment/activation	Cellular	Nov 28, 2017	Dec 1, 2017	Endocytic lysosomal uptake leading to liver fibrosis Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer AhR activation leading to liver fibrosis
1511	Lipid Peroxidation	Molecular	Apr 4, 2018	Apr 4, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
1395	Liver Cancer	Organ	May 30, 2017	Jun 19, 2021	Cyp2E1 Activation Leading to Liver Cancer
2034	liver dysfunction	Organ	Jul 20, 2022	Jul 20, 2022	The AOP framwork on silica nanopariticles induced hepatoxicity
1549	Liver Injury	Organ	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury IKK complex inhibition leading to liver injury Inhibition of N-linked glycosylation leads to liver injury
1389	Locomotor activity, decreased	Individual	May 2, 2017	May 18, 2017	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
2231	Locomotor function. Impaired	Population	Jun 6, 2024	Jun 6, 2024	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function
1498	Loss of alveolar capillary membrane integrity	Tissue	Jan 3, 2018	May 17, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis Lung surfactant function inhibition leading to decreased lung function
1675	Loss of barrier function	Tissue	Jul 3, 2019	Jul 3, 2019
2078	Loss of drebrin	Cellular	Dec 11, 2022	Jul 16, 2024	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons Various neuronal effects induced by elavl3, sox10, and mbp
319	Loss, Cochlear function	Organ	Nov 29, 2016	Sep 16, 2017	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1670	Lung cancer	Organ	Jul 3, 2019	Aug 13, 2019	Frustrated phagocytosis-induced lung cancer Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway Interaction with lung resident cell membrane components leads to lung cancer
1276	Lung fibrosis	Organ	Feb 15, 2017	Dec 26, 2017	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis Binding to ACE2 leading to lung fibrosis Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway
1246	Lung function, Decrease		Nov 29, 2016	Nov 29, 2016
1540	lysosomal disruption EMPTY	Molecular	Nov 12, 2018	Apr 17, 2024
1616	Malformation, cryptorchidism - maldescended testis	Organ	Apr 10, 2019	Jul 18, 2024	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals) Androgen receptor antagonism leading to testicular cancer Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis
348	Malformation, Male reproductive tract	Organ	Nov 29, 2016	Sep 16, 2017	PPARα activation in utero leading to impaired fertility in males
809	malformed, Male reproductive tract	Individual	Nov 29, 2016	Sep 16, 2017	HMG-CoA reductase inhibition leading to decreased fertility
2234	Malignant transformation of cells	Cellular	Jun 26, 2024	Jun 26, 2024
1822	Maturation of TNF/iNOS-Producing Dendritic Cells	Cellular	Nov 23, 2020	Nov 23, 2020	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
1941	Memory Loss	Individual	Oct 26, 2021	Oct 26, 2021	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
2145	Metabolic syndrome	Population	May 25, 2023	May 25, 2023	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome
2129	Metabolically unhealthy Obesity	Individual	Apr 5, 2023	Apr 5, 2023	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity
409	Metabolism of AFB1, Production of Reactive Electrophiles	Molecular	Nov 29, 2016	Sep 16, 2017	AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
987	Metaplasia of goblet cells	Molecular	Nov 29, 2016	Oct 5, 2020
1982	metastatic breast cancer	Organ	Mar 22, 2022	May 14, 2024	DNA damage and mutations leading to Metastatic Breast Cancer Activation of the AhR leading to metastatic breast cancer
2211	Microcephaly	Organ	Feb 2, 2024	Feb 2, 2024
1541	Mitochondrial Complex I inhibition	Molecular	Dec 19, 2018	Dec 19, 2018
1543	Mitochondrial Complex IV inhibition	Molecular	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury
1544	Mitochondrial Complex V inhibition	Molecular	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury
177	Mitochondrial dysfunction	Cellular	Nov 29, 2016	Apr 17, 2024	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Endocytic lysosomal uptake leading to liver fibrosis Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure Estrogen receptor activation leading to breast cancer Mitochondrial complex inhibition leading to liver injury Thermal stress leading to population decline (3) Thermal stress leading to population decline (2) Thermal stress leading to population decline (1) Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress Mitochondrial complexes inhibition leading to heart failure via decreased ATP production AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Renal protein alkylation leading to kidney toxicity Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis AOP from chemical insult to cell death AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment Immune mediated hepatitis Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome LXR activation leading to hepatic steatosis Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity Endocytotic lysosomal uptake leads to intestinal barrier disruption
1816	Mitochondrial dysfunction EMPTY	Cellular	Nov 2, 2020	Apr 17, 2024	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants
1547	Mitochondrial Injury	Cellular	Dec 19, 2018	Dec 19, 2018	Mitochondrial complex inhibition leading to liver injury Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
1195	modulation, Extracellular Matrix Composition	Cellular	Nov 29, 2016	Sep 16, 2017	Estrogen receptor activation leading to breast cancer
598	modulation, sodium channel	Molecular	Nov 29, 2016	Sep 16, 2017	Axonal sodium channel modulation leading to acute mortality
801	modulation, Unknown	Molecular	Nov 29, 2016	Dec 3, 2016	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription
1912	Motile Cilia Number/Length, Decreased	Cellular	Jul 23, 2021	Sep 10, 2021	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
1425	Mu Opioid Receptor Agonism	Molecular	Jun 8, 2017	Jun 8, 2017	Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition
1909	Mucociliary Clearance, Decreased	Individual	Jul 19, 2021	Sep 10, 2021	Oxidative stress Leading to Decreased Lung Function Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1
1245	Mucus , Hypersecretion		Nov 29, 2016	Nov 29, 2016
1244	Mucus hypersecretion,		Nov 29, 2016	Nov 29, 2016
1910	Mucus Viscosity, Increased	Organ	Jul 19, 2021	Sep 9, 2021
1843	Multi Organ Failure involving Acute Respiratory Distress Syndrome	Individual	Mar 19, 2021	Nov 19, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
1934	Myocardial Infarction	Organ	Oct 15, 2021	Oct 15, 2021	SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
312	N/A, Allergic contact dermatitis on challenge	Individual	Nov 29, 2016	Nov 29, 2016
27	N/A, Androgen receptor, Antagonism	Molecular	Nov 29, 2016	Sep 16, 2017	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
764	N/A, Ataxia, paralysis, or hyperactivity	Organ	Nov 29, 2016	Sep 16, 2017	Glutamate-gated chloride channel activation leading to acute mortality
1193	N/A, Breast Cancer	Individual	Nov 29, 2016	Feb 29, 2024	Estrogen receptor activation leading to breast cancer Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer
75	N/A, Covalent binding to protein, possibly lysine residue	Molecular	Nov 29, 2016	Sep 16, 2017
321	N/A, Cyanosis occurs	Individual	Nov 29, 2016	Dec 3, 2016	Oxidation of iron in hemoglobin leading to hematotoxicity
119	N/A, Gap	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading reproductive failure
139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects	Tissue	Nov 29, 2016	Nov 29, 2016	Sustained AhR Activation leading to Rodent Liver Tumours
590	N/A, hypoxia	Tissue	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to congenital malformations Succinate dehydrogenase inactivation leading to cancer
337	N/A, Impairment of reproductive capacity	Individual	Nov 29, 2016	Dec 3, 2016	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)
158	N/A, Interferences with SH-/selen-proteins	Cellular	Nov 29, 2016	Sep 16, 2017
344	N/A, Liver fibrosis	Organ	Nov 29, 2016	Dec 5, 2018	Protein Alkylation leading to Liver Fibrosis Endocytic lysosomal uptake leading to liver fibrosis Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis AhR activation leading to liver fibrosis
345	N/A, Liver Steatosis	Organ	Nov 29, 2016	Sep 16, 2017	LXR activation leading to hepatic steatosis
173	N/A, Methemoglobinemia, decreased hemoglobin, hematocrit, red blood cell number	Organ	Nov 29, 2016	Sep 16, 2017	Oxidation of iron in hemoglobin leading to hematotoxicity
352	N/A, Neurodegeneration	Tissue	Nov 29, 2016	Feb 23, 2021	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 Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Acetylcholinesterase Inhibition Leading to Neurodegeneration 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 Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis Various neuronal effects induced by elavl3, sox10, and mbp
213	N/A, Parent compound is converted to the reactive metabolite and forms free radicals leading to oxidation of heme iron(II) in hemoglobin to iron(III)	Molecular	Nov 29, 2016	Dec 3, 2016	Oxidation of iron in hemoglobin leading to hematotoxicity
253	N/A, Reproductive failure	Individual	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading reproductive failure
634	N/A, sedation	Individual	Nov 29, 2016	Dec 3, 2016	Histamine (H2) receptor antagonism leading to reduced survival
1489	N/A, Steatohepatisis	Organ	Nov 13, 2017	Nov 27, 2017	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH) G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
294	N/A, Unknown	Molecular	Nov 29, 2016	Sep 16, 2017	Kidney toxicity induced by activation of 5HT2C Uncharacterized liver damage leading to hepatocellular carcinoma
1259	narcosis	Cellular	Feb 7, 2017	Sep 16, 2017	AOP from chemical insult to cell death
1263	Necrosis	Tissue	Feb 7, 2017	Feb 7, 2017	AOP from chemical insult to cell death
1548	Necrotic Tissue	Tissue	Dec 19, 2018	Mar 7, 2019	Mitochondrial complex inhibition leading to liver injury IKK complex inhibition leading to liver injury
1557	Neural crest cell migration, reduced	Cellular	Dec 20, 2018	Dec 20, 2018	Histone deacetylase inhibition leads to impeded craniofacial development Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
1561	Neural tube defects	Tissue	Dec 20, 2018	Dec 20, 2018	Histone deacetylase inhibition leads to neural tube defects Ceramide synthase inhibition leading to neural tube defects
1514	Neurodegeneration	Organ	Apr 4, 2018	Apr 4, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
1436	neurogenic inflammation of sensory nerves	Cellular	Jun 27, 2017	Jun 27, 2017
188	Neuroinflammation	Tissue	Nov 29, 2016	Jul 15, 2022	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 Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits 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 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 A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms Various neuronal effects induced by elavl3, sox10, and mbp Binding and activation of GPER leading to learning and memory impairments
2150	Neurological disorder	Individual	Jun 15, 2023	Jun 15, 2023	Increased LCN2/iron complex leading to neurological disorders Excessive iron accumulation leading to neurological disorders Various neuronal effects induced by elavl3, sox10, and mbp
191	Neuronal dysfunction	Cellular	Nov 29, 2016	Apr 7, 2022	Increased LCN2/iron complex leading to neurological disorders Various neuronal effects induced by elavl3, sox10, and mbp
1915	Neutrophil activation, Increased	Cellular	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
1417	NFE2/Nrf2 repression	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction
1786	Nipple retention (NR), increased	Individual	May 11, 2020	Jan 11, 2023	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring
1895	NLRP3 inflammasome activity, increased	Molecular	Jun 25, 2021	Jun 25, 2021	SARS-CoV-2 infection leading to hyperinflammation SARS-CoV-2 infection leading to pyroptosis Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
2019	Non-alcoholic fatty liver disease	Individual	Jun 27, 2022	Jun 27, 2022	PM2.5-related AOP frameworks on liver diseases
2007	Non-coding RNA expression profile alteration	Molecular	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity
1235	Non-neuronal production of IL-8/CXCL1, Epithelial irritation	Tissue	Nov 29, 2016	Dec 3, 2016
1224	Non-neuronal production of TNF, Epithelial irritation	Individual	Nov 29, 2016	Dec 3, 2016
862	Not Increased, Circulating Ketone Bodies	Tissue	Nov 29, 2016	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
1466	Notochord distortion or malformations	Organ	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1447	obesity	Individual	Jul 24, 2017	Jul 24, 2017	Epigenetic modification of PPARG leading to adipogenesis
2083	Occurrence of Cataracts	Organ	Dec 18, 2022	Mar 8, 2024	Deposition of energy leading to occurrence of cataracts
2096	Occurrence, (Micro)vascular dysfunction	Tissue	Jan 23, 2023	Jul 31, 2023	Viral spike protein interaction with ACE2 leads to microvascular dysfunction, via ACE2 dysregulation
616	Occurrence, A paroxysmal depolarizing shift	Tissue	Nov 29, 2016	Apr 29, 2019	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
2069	Occurrence, Abnormal Vascular Remodeling	Organ	Oct 17, 2022	Sep 17, 2024	Deposition of energy leads to abnormal vascular remodeling
835	Occurrence, Ballooning degeneration (hepatocyte)	Cellular	Nov 29, 2016	Sep 16, 2017	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
2091	Occurrence, Bone Loss	Organ	Jan 11, 2023	Aug 23, 2024	Deposition of energy leading to occurrence of bone loss
1106	Occurrence, cardiac arrhythmia	Organ	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality Organic anion transporter (OAT1) inhibition leading to renal failure and mortality unknown MIE leading to renal failure and mortality
1100	Occurrence, cardiac arrthymia		Nov 29, 2016	Nov 29, 2016
823	Occurrence, Cystic dilatation (renal tubule)	Organ	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
836	Occurrence, Cytoplasmic vacuolization (Bile duct cell)	Cellular	Nov 29, 2016	Sep 16, 2017	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
833	Occurrence, Cytoplasmic vacuolization (hepatocyte)	Cellular	Nov 29, 2016	Sep 16, 2017	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
837	Occurrence, Cytoplasmic vacuolization (kupffer cell)	Cellular	Nov 29, 2016	Sep 16, 2017	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
824	Occurrence, Cytoplasmic vacuolization (podocyte)	Organ	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
818	Occurrence, Cytoplasmic vacuolization (Renal tubule)	Organ	Nov 29, 2016	Sep 16, 2017	Kidney dysfunction by decreased thyroid hormone
613	Occurrence, Epileptic seizure	Individual	Nov 29, 2016	Apr 29, 2019	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
1623	Occurrence, Focal Seizure	Tissue	Apr 22, 2019	May 20, 2020	Acetylcholinesterase Inhibition Leading to Neurodegeneration
921	Occurrence, Hyperplasia of goblet cells	Tissue	Nov 29, 2016	Sep 21, 2021
814	Occurrence, Kidney toxicity	Organ	Nov 29, 2016	Mar 4, 2022	Kidney dysfunction by decreased thyroid hormone Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity Renal protein alkylation leading to kidney toxicity Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
920	Occurrence, Metaplasia of goblet cells	Tissue	Nov 29, 2016	Aug 23, 2021
1105	Occurrence, renal ischemia	Tissue	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
1097	Occurrence, renal proximal tubular necrosis	Tissue	Nov 29, 2016	Sep 16, 2017	Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality unknown MIE leading to renal failure and mortality Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
1102	Occurrence, tophi (urate) deposition	Tissue	Nov 29, 2016	Dec 3, 2016	Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
919	Occurrence, Transdifferentiation of ciliated epithelial cells	Cellular	Nov 29, 2016	Aug 17, 2021
1872	Olfactory epithelium degeneration	Tissue	Apr 25, 2021	Mar 30, 2022	SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
1871	olfactory sensory neurons, decrease	Cellular	Apr 25, 2021	Mar 30, 2022	SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
1218	Opening of calcium channel, Calcium influx	Cellular	Nov 29, 2016	Oct 25, 2017	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1427	Opening of G protein gated inward rectifying K channels	Cellular	Jun 8, 2017	Jun 8, 2017	Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
2187	Opening, voltage-gated calcium channels	Molecular	Sep 14, 2023	Sep 14, 2023	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
2042	Orofacial clefting	Individual	Jul 27, 2022	May 16, 2023	Antagonism of Smoothened receptor leading to orofacial clefting Decrease, GLI1/2 target gene expression leads to orofacial clefting Decrease, cholesterol synthesis leads to orofacial clefting
1151	Osteoporosis and vascular calcification, Bone deterioration	Individual	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
601	Overactivation, muscle contraction	Tissue	Nov 29, 2016	Sep 16, 2017	Axonal sodium channel modulation leading to acute mortality
600	Overactivation, Neuronotransmitter release	Molecular	Nov 29, 2016	Sep 16, 2017	Axonal sodium channel modulation leading to acute mortality
388	Overactivation, NMDARs	Cellular	Nov 29, 2016	Jul 14, 2024	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment. Acetylcholinesterase Inhibition Leading to Neurodegeneration Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons Various neuronal effects induced by elavl3, sox10, and mbp
1886	Overexpression of rasl11b	Molecular	May 28, 2021	Dec 8, 2021	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)
664	Overwhelmed, Mitochondrial DNA repair mechanisms	Cellular	Nov 29, 2016	Sep 16, 2017	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure
971	Ovulation of oocytes Reduced, Delayed, or Blocked, Decrease or delay in LH surge required for ovulation	Individual	Nov 29, 2016	May 19, 2020	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
1596	Oxidation of DNA	Cellular	Feb 3, 2019	Feb 3, 2019
1594	Oxidation of membrane lipids	Cellular	Feb 3, 2019	Jul 4, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
926	Oxidation, Glutathione (To be considered with MIE)	Molecular	Nov 29, 2016	Nov 9, 2017	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure
844	Oxidation, Uroporphyrinogen	Cellular	Nov 29, 2016	Sep 16, 2017	Aryl hydrocarbon receptor activation leading to uroporphyria
1595	Oxidation/denatuation of membrane proteins	Cellular	Feb 3, 2019	Jul 4, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
1520	Oxidative phosphorylation	Cellular	May 24, 2018	May 24, 2018
1392	Oxidative Stress	Molecular	May 30, 2017	Aug 26, 2024	Cyp2E1 Activation Leading to Liver Cancer 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 Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Oxidative stress Leading to Decreased Lung Function Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1 A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Adverse outcome pathway of PM-induced respiratory toxicity Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Deposition of energy leads to abnormal vascular remodeling Deposition of energy leading to occurrence of cataracts Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases. Deposition of energy leading to occurrence of bone loss Deposition of Energy Leading to Learning and Memory Impairment Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway Essential element imbalance leads to reproductive failure via oxidative stress Calcium-mediated neuronal ROS production and energy imbalance Increased reactive oxygen species production leading to decreased cognitive function Deposition of ionizing energy leads to population decline via impaired meiosis Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity Binding and activation of GPER leading to learning and memory impairments Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat. Organic anion transporter (OAT1) inhibition leading to renal failure and mortality Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality unknown MIE leading to renal failure and mortality Estrogen receptor activation leading to breast cancer Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction Demethylation of PPAR promotor leading to vascular disrupting effects The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways CYP2E1 activation and formation of protein adducts leading to neurodegeneration Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality Excessive iron accumulation leading to neurological disorders Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production Various neuronal effects induced by elavl3, sox10, and mbp Oxidation of iron in hemoglobin leading to hematotoxicity
1510	Oxidative Stress in Brain	Molecular	Apr 4, 2018	Apr 4, 2018
1231	Oxidization of biomolecules, Lipid bilayer and cellular proteins		Nov 29, 2016	Nov 29, 2016
1504	p21 (CDKN1A) expression, increase	Cellular	Jan 21, 2018	Nov 26, 2018
1725	Pancreatic acinar cell tumors	Molecular	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
896	Parkinsonian motor deficits	Individual	Nov 29, 2016	Mar 12, 2018	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits Various neuronal effects induced by elavl3, sox10, and mbp
209	Peptide Oxidation	Molecular	Nov 29, 2016	Nov 13, 2017	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat) Peptide Oxidation Leading to Hypertension Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
1947	Pericyte dysfunction	Cellular	Oct 28, 2021	Oct 28, 2021	SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction.
2095	Periventricular heterotopia formation	Individual	Jan 19, 2023	Jan 19, 2023	Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
228	peroxisome proliferator activated receptor promoter demethylation	Molecular	Nov 29, 2016	Sep 16, 2017	LXR activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis Epigenetic modification of PPARG leading to adipogenesis Demethylation of PPAR promotor leading to vascular disrupting effects
1086	persistent, cytotoxicity (pleura or peritoneum)	Cellular	Nov 29, 2016	Sep 16, 2017	Chronic cytotoxicity of the serous membrane leading to pleural/peritoneal mesotheliomas in the rat.
1289	Perturbation of cholesterol	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
2182	Phenotype switching of vascular smooth muscle cells	Cellular	Sep 4, 2023	Sep 4, 2023
1518	Photosynthesis, Decrease	Cellular	May 24, 2018	May 24, 2018
1091	Physical and/or chemical interaction with cellular components,		Nov 29, 2016	Nov 29, 2016
1794	Pin-1 activation	Cellular	Jul 9, 2020	Jul 9, 2020	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1639	Plasma RA level decreased	Tissue	May 22, 2019	May 22, 2019
1914	Platelet activation, Increased	Cellular	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
1857	Platelet-neutrophil interactions, Increased	Cellular	Apr 8, 2021	Apr 8, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Endothelial cell dysfunction leading to thromboinflammation
1754	Porcupine-induced Wnt secretion and Wnt signaling activation	Cellular	Mar 23, 2020	Nov 25, 2022	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
1979	Premature cell differentiation	Organ	Mar 21, 2022	Mar 21, 2022	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation
1889	Premature initiation of meiosis in fetal male germ cells	Cellular	May 29, 2021	Nov 11, 2021	Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
1146	premature, Spawning	Individual	Nov 29, 2016	Jan 17, 2017
1144	premature, spawning 1 1		Nov 29, 2016	Nov 29, 2016
1064	prepubertal increase, Estrogen receptor (ER) activity	Molecular	Nov 29, 2016	Dec 3, 2016	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
1232	Production of nerve growth factor ,		Nov 29, 2016	Nov 29, 2016
1234	Production of nerve growth factor , Epithelial irritation	Tissue	Nov 29, 2016	Dec 3, 2016
1274	Production of α-smooth muscle actin	Cellular	Feb 15, 2017	Feb 15, 2017
77	Production, Critical Metabolites (CGA 330050 and CGA 265307)	Cellular	Nov 29, 2016	Sep 16, 2017	Inhibition of iNOS, hepatotoxicity, and regenerative proliferation leading to liver tumors
1233	Production, Nerve growth factor		Nov 29, 2016	Nov 29, 2016
249	Production, Reactive oxygen species	Tissue	Nov 29, 2016	Dec 3, 2016	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
302	Production, VEGF-A		Nov 29, 2016	Nov 29, 2016
2185	Proliferation of vascular smooth muscle cells	Cellular	Sep 5, 2023	Sep 5, 2023
57	Proliferation, Cell proliferation in the absence of cytotoxicity	Cellular	Nov 29, 2016	Sep 16, 2017	Uncharacterized liver damage leading to hepatocellular carcinoma
1041	Proliferation, smooth muscle		Nov 29, 2016	Nov 29, 2016
1067	Proliferation/Clonal Expansion, aberrant basal cells	Cellular	Nov 29, 2016	Sep 16, 2017	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
1042	Proliferation/Clonal Expansion, smooth muscle	Cellular	Nov 29, 2016	Sep 16, 2017	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
1961	Prolongation of Action Potential Duration	Organ	Dec 13, 2021	Jan 29, 2023	hERG channel blockade leading to sudden cardiac death
1962	Prolongation of QT interval	Organ	Dec 13, 2021	Dec 13, 2021	hERG channel blockade leading to sudden cardiac death
1842	Prolonged TLR9 activation	Molecular	Mar 19, 2021	Mar 26, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
599	prolonged, Depolarization of neuronal membrane	Cellular	Nov 29, 2016	Sep 16, 2017	Axonal sodium channel modulation leading to acute mortality
1061	prolonged, elevation of serun CCK	Tissue	Nov 29, 2016	Sep 16, 2017	PPARalpha activation leading to pancreatic acinar tumors in the rat and mouse
1075	prolonged, estrus	Individual	Nov 29, 2016	Dec 3, 2016	GnRH pulse disruption leading to mammary adenomas and carcinomas in the SD rat. GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
334	Promotion, Hepatocelluar carcinoma	Individual	Nov 29, 2016	Sep 16, 2017	Uncharacterized liver damage leading to hepatocellular carcinoma
1044	Promotion, mesovarian leiomyomas	Tissue	Nov 29, 2016	Sep 16, 2017	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
1053	Promotion, ovarian adenomas	Tissue	Nov 29, 2016	Dec 3, 2016	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
2092	Promotion, Ovarian Cancer	Organ	Jan 12, 2023	Mar 11, 2023	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
1054	Promotion, ovarian granular cell tumors	Cellular	Nov 29, 2016	Dec 3, 2016	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse
1066	Promotion, SIX-1 postive basal-type progenitor cells	Cellular	Nov 29, 2016	Sep 16, 2017	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
211	Propagation, Oxidative stress	Molecular	Nov 29, 2016	Sep 16, 2017
2135	Prostate cancer	Individual	May 11, 2023	May 11, 2023	Androgen receptor activation leading to prostate cancer
2136	prostatic intraepithelial neoplasia	Tissue	May 11, 2023	May 11, 2023	Androgen receptor activation leading to prostate cancer
1585	Proteasomal dysfunction	Molecular	Jan 30, 2019	Jan 30, 2019	α-diketone-induced bronchiolitis obliterans Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
1509	Protein Adduct Formation	Molecular	Mar 26, 2018	Mar 26, 2018	CYP2E1 activation and formation of protein adducts leading to neurodegeneration
2029	protein-coupled estrogen receptor 1 (GPER) activation	Molecular	Jul 18, 2022	Jul 18, 2022	G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects Binding and activation of GPER leading to learning and memory impairments
1709	Psoriatic skin disease	Individual	Dec 27, 2019	Nov 23, 2020	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
2085	Pulmonary epithelial injury	Cellular	Jan 9, 2023	Jul 11, 2023	AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1458	Pulmonary fibrosis	Organ	Jul 26, 2017	May 12, 2023	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1092	Pulmonary Fibrosis,		Nov 29, 2016	Nov 29, 2016
2010	Pulmonary inflammation	Organ	May 31, 2022	May 31, 2022	Adverse outcome pathway of PM-induced respiratory toxicity AOPs of amorphous silica nanoparticles: ROS-mediated oxidative stress increased respiratory dysfunction and diseases.
1967	Pyroptosis	Cellular	Jan 18, 2022	Jan 19, 2022	SARS-CoV-2 infection leading to pyroptosis
1593	Radicals of target chemicals	Molecular	Feb 3, 2019	Feb 3, 2019
1484	Receptor mediated endocytosis	Molecular	Oct 25, 2017	Oct 25, 2017
1329	Reduce expression, BDNF (Brain-derived neurotrophic factor)	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation Serotonin transporter activation to agitation Serotonin transporter activation to depression
1757	Reduce, Sperm count	Individual	Apr 6, 2020	Apr 6, 2020	Alkylation of DNA leading to reduced sperm count Increased (ectopic) concentration of all-trans retinoic acid (ATRA) if fetal testis leading to reduced sperm count, males
2024	Reduced complex sphingolipids	Cellular	Jul 14, 2022	Jul 19, 2022	Ceramide synthase inhibition leading to neural tube defects
2210	Reduced cortical thickness	Tissue	Feb 2, 2024	Feb 2, 2024	Retinoic acid receptor agonism during neurodevelopment leading to microcephaly
945	reduced dimerization, ARNT/HIF1-alpha	Molecular	Nov 29, 2016	Mar 23, 2018	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF AhR activation leading to preeclampsia
966	Reduced Estradiol in Circulation, Reduced steroidogenic production of estradiol in granulosa cells leading to decreased estradiol in circulation	Tissue	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
1135	Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction	Tissue	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
381	Reduced levels of BDNF	Molecular	Nov 29, 2016	Apr 4, 2019	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment 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
2223	Reduced number of oligodendrocytes	Cellular	Apr 12, 2024	Apr 12, 2024	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory
948	reduced production, VEGF	Cellular	Nov 29, 2016	Mar 28, 2018	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF AhR activation leading to preeclampsia
1883	Reduced size of the ovarian reserve	Organ	May 24, 2021	Aug 6, 2024	Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary
1677	Reduced tidal volume	Organ	Jul 3, 2019	Feb 16, 2021	Lung surfactant function inhibition leading to decreased lung function
674	Reduced, Ability to attract spawning mates	Individual	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
1007	Reduced, Anterior swim bladder inflation	Organ	Nov 29, 2016	Oct 7, 2022	Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
580	Reduced, Antiseptic incorporated in food	Population	Nov 29, 2016	Dec 3, 2016	Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
1335	Reduced, BDNF (Brain-derived neurotrophic factor)	Molecular	Apr 13, 2017	May 31, 2017	Network of SSRIs (selective serotonin reuptake inhibitors) Mental stress to depression Mental stress to agitation
565	Reduced, Brood care	Population	Nov 29, 2016	Dec 3, 2016	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1 Abnormal role change in worker caste contributes to reduced brood care and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2
1424	Reduced, fatty acid beta oxidation	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
587	Reduced, feeding 1	Individual	Nov 29, 2016	Nov 29, 2016	Sodium channel inhibition leading to reduced survival Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
1017	Reduced, Feeding 2		Nov 29, 2016	Nov 29, 2016
561	Reduced, Food storage	Population	Nov 29, 2016	Dec 3, 2016	Decrease Glucose oxidase activity contributes to reduction of antiseptic in food and leads to colony loss/failure
1419	Reduced, FXR activity	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
1415	Reduced, GABA-A receptor activation	Molecular	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
689	Reduced, Gonadotropin releasing hormone, hypothalamus	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
1008	Reduced, Hearing	Organ	Nov 29, 2016	Feb 18, 2019	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
1423	Reduced, HSD17B4 activity	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
690	Reduced, Luteinizing hormone (LH), plasma	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
692	Reduced, Maturation inducing steroid receptor signalling, oocyte	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
691	Reduced, Maturation inducing steroid, plasma	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
694	Reduced, Meiotic prophase I/metaphase I transition, oocyte	Cellular	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
1405	Reduced, mucosal defense	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer Helicobacter pylori to gastric ulcer
1212	Reduced, Neuronal synaptic inhibition	Cellular	Nov 29, 2016	Dec 3, 2016
678	Reduced, Pheromone release	Individual	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
1403	Reduced, platelet aggregation	Tissue	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
1004	Reduced, Posterior swim bladder inflation	Organ	Nov 29, 2016	Oct 7, 2022	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
1422	Reduced, PPARalpha	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
1413	Reduced, presynaptic neuron 2 activity	Cellular	Jun 2, 2017	Jun 2, 2017	presynaptic neuron 2 repression to epilepsy
383	Reduced, Presynaptic release of glutamate	Molecular	Nov 29, 2016	Sep 16, 2017	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
687	Reduced, Prostaglandin E2 concentration, hypothalamus	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
671	Reduced, Prostaglandin F2alpha concentration, plasma	Individual	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release
672	Reduced, Prostaglandin F2alpha synthesis, ovary	Organ	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
685	Reduced, Prostaglandins, ovary	Organ	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction
1402	Reduced, PTGS1 function	Molecular	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS1 inactivation to gastric ulcer
1408	Reduced, PTGS2 function	Cellular	Jun 2, 2017	Jun 2, 2017	NSAID induced PTGS2 inactivation to gastric ulcer
675	Reduced, Reproductive Success	Individual	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release Cyclooxygenase inhibition leading to reproductive dysfunction Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
1420	Reduced, SHP activity	Molecular	Jun 2, 2017	Jun 2, 2017	NFE2/Nrf2 repression to steatosis
673	Reduced, Spawning behavior	Individual	Nov 29, 2016	Dec 3, 2016	Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior
592	Reduced, survival	Population	Nov 29, 2016	Dec 3, 2016	Sodium channel inhibition leading to reduced survival Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
1005	Reduced, Swimming performance	Individual	Nov 29, 2016	Sep 8, 2021	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration
586	Reduced, swimming speed	Individual	Nov 29, 2016	Nov 29, 2016	Sodium channel inhibition leading to reduced survival sodium channel inhibition leading to increased predation Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival
1631	Reduction fo Pigmentation pattern	Individual	May 3, 2019	May 3, 2019	Inhibition of tyrosinase leads to decreased population in fish
1626	reduction in melanin lead to decrease of pigmentation	Tissue	May 3, 2019	May 3, 2019
1629	Reduction in melanin level	Cellular	May 3, 2019	May 3, 2019	Inhibition of tyrosinase leads to decreased population in fish
965	reduction in ovarian granulosa cells synthesis of estradiol, Reduced steroidogenic production of estradiol in granulosa cells	Cellular	Nov 29, 2016	Dec 3, 2016	Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
408	reduction in ovarian granulosa cells, Aromatase (Cyp19a1)	Cellular	Nov 29, 2016	May 28, 2021	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female
29	Reduction in, Angiogenic sprouts		Nov 29, 2016	Nov 29, 2016
1464	Reduction of collagen crosslinking	Tissue	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1628	Reduction of L-Dopaquinone	Cellular	May 3, 2019	May 3, 2019	Inhibition of tyrosinase leads to decreased population in fish
1625	Reduction of L-Dopaquinone leads to melanin reduction	Cellular	May 3, 2019	May 3, 2019
1630	Reduction of melanosome level	Tissue	May 3, 2019	May 3, 2019	Inhibition of tyrosinase leads to decreased population in fish
1610	Reduction, 17-OH-pregnenolone conversion in DHEA	Cellular	Apr 10, 2019	Apr 10, 2019	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
1611	Reduction, 17-OH-progesterone conversion in androstenedione	Cellular	Apr 10, 2019	Apr 10, 2019	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)
3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Cellular	Nov 29, 2016	Sep 16, 2017	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Aromatase inhibition leading to reproductive dysfunction Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad	Cellular	Jun 15, 2020	Jul 13, 2022	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation
28	Reduction, Angiogenesis	Molecular	Nov 29, 2016	Jul 20, 2022	Disruption of VEGFR Signaling Leading to Developmental Defects
49	Reduction, Ca and HCO3 transport to shell gland	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading reproductive failure
447	Reduction, Cholesterol transport in mitochondria	Cellular	Nov 29, 2016	Sep 16, 2017	PPARα activation leading to impaired fertility in adult male rodents PPARα activation in utero leading to impaired fertility in males
78	Reduction, Cumulative fecundity and spawning	Individual	Nov 29, 2016	Mar 20, 2017	Estrogen receptor agonism leading to reproductive dysfunction Aromatase inhibition leading to reproductive dysfunction Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Estrogen receptor antagonism leading to reproductive dysfunction Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Inhibition of thyroid peroxidase leading to impaired fertility in fish Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Inhibition of 5α-reductase leading to impaired fecundity in female fish Deposition of energy leading to population decline via DNA strand breaks and follicular atresia Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosis Deposition of energy leading to population decline via DNA oxidation and follicular atresia Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
1618	Reduction, egg production and spawning	Individual	Apr 18, 2019	Apr 18, 2019
106	Reduction, Eggshell thickness	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading reproductive failure
446	Reduction, fetal/adult testosterone	Tissue	Nov 29, 2016	May 17, 2023	Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity
129	Reduction, Gonadotropins, circulating concentrations	Organ	Nov 29, 2016	May 9, 2018	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
64	Reduction, Ionotropic GABA receptor chloride channel conductance	Cellular	Nov 29, 2016	Feb 6, 2018	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
669	Reduction, Neuronal synaptic inhibition	Cellular	Nov 29, 2016	May 16, 2018	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
981	Reduction, NFAT/AP-1 complex formation	Cellular	Nov 29, 2016	Jun 27, 2021	Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
219	Reduction, Plasma 17beta-estradiol concentrations	Organ	Nov 29, 2016	Sep 26, 2017	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female Aromatase inhibition leading to reproductive dysfunction Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Inhibition of thyroid peroxidase leading to impaired fertility in fish Inhibition of 5α-reductase leading to impaired fecundity in female fish Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
1693	Reduction, Plasma progesterone concentration	Tissue	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
221	Reduction, Plasma vitellogenin concentrations	Organ	Nov 29, 2016	Sep 16, 2017	Aromatase inhibition leading to reproductive dysfunction Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Estrogen receptor antagonism leading to reproductive dysfunction Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Inhibition of thyroid peroxidase leading to impaired fertility in fish Inhibition of 5α-reductase leading to impaired fecundity in female fish Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
1692	Reduction, Progesterone synthesis	Cellular	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
1694	Reduction, progesterone uptake, decresed maturation	Cellular	Oct 3, 2019	Oct 3, 2019	Luteinizing hormone receptor antagonism leading to reproductive dysfunction
243	Reduction, Prostaglandin E2 concentration	Tissue	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading reproductive failure
274	Reduction, Testosterone synthesis by ovarian theca cells	Cellular	Nov 29, 2016	Sep 16, 2017	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
413	Reduction, Testosterone synthesis in Leydig cells	Cellular	Nov 29, 2016	Sep 16, 2017	PPARα activation leading to impaired fertility in adult male rodents PPARα activation in utero leading to impaired fertility in males Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
2139	Reduction, the ratio of 17beta-estradiol/11-Keto Testosterone in plasma	Organ	May 16, 2023	May 16, 2023	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
309	Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	Cellular	Nov 29, 2016	Sep 16, 2017	Aromatase inhibition leading to reproductive dysfunction Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Estrogen receptor antagonism leading to reproductive dysfunction Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
285	Reduction, Vitellogenin synthesis in liver	Tissue	Nov 29, 2016	May 27, 2021	Aromatase inhibition leading to reproductive dysfunction Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) Estrogen receptor antagonism leading to reproductive dysfunction Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
1040	relaxation, smooth muscle	Tissue	Nov 29, 2016	Dec 3, 2016	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
1426	Release of G Proteins	Cellular	Jun 8, 2017	Jun 8, 2017	Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
1219	Release of Substance P (SP), Substance P increase in circulation		Nov 29, 2016	Nov 29, 2016
87	Release, Cytokine	Cellular	Nov 29, 2016	Sep 16, 2017	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11) Frustrated phagocytosis-induced lung cancer Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Endothelial cell dysfunction leading to thromboinflammation
2031	Releasing, Apoptosis-Inducing Factor (AIF)	Molecular	Jul 18, 2022	Jul 18, 2022	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
985	Relief, Relief of atopic dermatitis	Individual	Nov 29, 2016	Dec 3, 2016
1358	Repress, GABA-A receptor	Molecular	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy
495	Repressed expression of steroidogenic enzymes	Cellular	Nov 29, 2016	Sep 16, 2017	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
1902	Repression of Gbx2 expression	Molecular	Jul 14, 2021	Oct 7, 2021	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
1277	Reproductive failure	Individual	Feb 15, 2017	Feb 15, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
445	Respiratory distress/arrest	Organ	Nov 29, 2016	Dec 20, 2019	Acetylcholinesterase inhibition leading to acute mortality Sodium channel inhibition leading to congenital malformations
397	Response, Keratinocytes	Cellular	Nov 29, 2016	Nov 29, 2016
1637	Retinaldehyde dehydrogenase inhibition	Molecular	May 22, 2019	May 22, 2019	Inhibition of retinaldehyde dehydrogenase leads to population decline
1638	Retinoic acid (RA) synthesis decreased	Cellular	May 22, 2019	May 22, 2019
1278	ROS formation	Molecular	Feb 15, 2017	Sep 16, 2017	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway
1592	ROS generation from photoactivated chemicals	Molecular	Feb 3, 2019	Jul 4, 2019	Adverse outcome pathway on photochemical toxicity initiated by light exposure
2186	Ryanodine receptor activation	Molecular	Sep 8, 2023	Sep 8, 2023	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms
1738	SARS-CoV-2 cell entry	Cellular	Mar 1, 2020	Apr 4, 2023	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia) Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke) SARS-CoV-2 infection leading to hyperinflammation SARS-CoV-2 infection leading to pyroptosis SARS-CoV-2 spike protein binding to ACE2 receptors expressed on pericytes leads to endothelial cell dysfunction, microvascular injury and myocardial infarction. Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
1601	Scaling, Lichenification	Organ	Feb 3, 2019	Feb 3, 2019
2006	Secondary genotoxicity	Cellular	May 25, 2022	May 25, 2022	Interaction with lung resident cell membrane components leads to lung cancer
1437	Sensing of the stressor by pulmonary cells	Molecular	Jun 29, 2017	Jun 29, 2017
827	sensitisation, skin	Organ	Nov 29, 2016	Nov 29, 2016	Covalent Protein binding leading to Skin Sensitisation
1237	Sensitization, Immune system	Individual	Nov 29, 2016	Dec 3, 2016
1583	Sensory axonal peripheral neuropathy	Individual	Jan 29, 2019	Jan 29, 2019	Microtubule interacting drugs lead to peripheral neuropathy Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality Various neuronal effects induced by elavl3, sox10, and mbp
1431	Serotonin 1A Receptor Agonism	Molecular	Jun 23, 2017	Jun 23, 2017	Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
1390	Sexual behavior, decreased	Individual	May 3, 2017	May 17, 2017	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
1904	six1b expression, increased	Molecular	Jul 14, 2021	Aug 12, 2021	GSK3beta inactivation leading to increased mortality via defects in developing inner ear
417	skewed, sex ratio	Population	Nov 29, 2016	Dec 3, 2016	ER agonism leading to skewed sex ratios due to altered sexual differentiation in males
1649	Snail, Zeb, Twist activation	Molecular	May 29, 2019	May 29, 2019
1222	SP (Substance P) release, Local increase of SP	Cellular	Nov 29, 2016	Sep 16, 2017	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1515	Spermatocyte depletion	Tissue	May 2, 2018	Jul 28, 2021	Histone deacetylase inhibition leading to testicular atrophy
1068	squamous metaplasia, aberrant basal cells	Tissue	Nov 29, 2016	Dec 3, 2016	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.
999	stabilization, co-repressor		Nov 29, 2016	Nov 29, 2016
1000	stabilization, PPAR alpha co-repressor	Molecular	Nov 29, 2016	Apr 30, 2019	Antagonist binding to PPARα leading to body-weight loss
1788	Status epilepticus	Individual	May 21, 2020	May 21, 2020	Acetylcholinesterase Inhibition Leading to Neurodegeneration
650	Stimulation of adult Leydig cells via the Adrenal Corticosterone, Increased Glucocorticoid	Molecular	Nov 29, 2016	Dec 3, 2016	Modulation of Adult Leydig Cell Function Subsequent to Glucocorticoid Activation
1706	Stimulation, TLR7/8	Molecular	Dec 27, 2019	Nov 21, 2020	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease
2226	Stressor binding PPAR isoforms	Molecular	May 8, 2024	May 22, 2024	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis
1671	Substance - lung surfactant interaction	Molecular	Jul 3, 2019	Jul 3, 2019
1495	Substance interaction with the lung resident cell membrane components	Molecular	Jan 2, 2018	May 17, 2023	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis Interaction with lung resident cell membrane components leads to lung cancer Substance interaction with lung resident cell membrane components leading to atherosclerosis
2243	Succinate Accumulation	Cellular	Jul 18, 2024	Jul 18, 2024	Succinate dehydrogenase inactivation leading to cancer
2118	Succinate dehydrogenase, inhibited	Molecular	Apr 3, 2023	May 4, 2023	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress Succinate dehydrogenase inactivation leading to cancer
1964	Sudden cardiac death	Individual	Dec 13, 2021	Dec 13, 2021	hERG channel blockade leading to sudden cardiac death
2120	Superoxide generation, increased	Cellular	Apr 3, 2023	Apr 17, 2023	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine
1565	Suppressed AP-1	Cellular	Dec 24, 2018	Dec 24, 2018
1567	Suppressed DC activation	Organ	Dec 24, 2018	Dec 24, 2018
1573	Suppressed MyD88	Cellular	Jan 6, 2019	Mar 17, 2019
1566	Suppressed NF-kB	Cellular	Dec 24, 2018	Dec 24, 2018
1701	Suppression of NF-kB	Molecular	Nov 17, 2019	Nov 17, 2019
1702	Suppression of T cell activation	Cellular	Nov 17, 2019	Mar 6, 2023	Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response
1718	Suppression of IL-4 production	Cellular	Jan 5, 2020	Feb 24, 2021	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
1717	Suppression of STAT5 binding to cytokine gene promoters	Cellular	Jan 5, 2020	Feb 24, 2021	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response
456	Suppression, Constitutive androstane receptor, NR1l3	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis
1046	Suppression, Estrogen receptor (ER) activity	Molecular	Nov 29, 2016	Feb 28, 2022	Antiestrogen activity leading to ovarian adenomas and granular cell tumors in the mouse Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia
461	Suppression, HNF4alpha	Molecular	Nov 29, 2016	Sep 16, 2017	HNF4alpha suppression leading to hepatic steatosis
1202	Suppression, IL-2 and IL-4 production	Cellular	Nov 29, 2016	Jun 27, 2021	Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
403	Suppression, Immune system	Individual	Nov 29, 2016	Dec 3, 2016	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility Suppression of immune system contributes to impaired development and leads to colony loss/failure Suppression of immune system contributes to abnormal foraging and leads to colony loss/failure Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia
152	Suppression, Inflammatory cytokines	Individual	Nov 29, 2016	Dec 3, 2016	Glucocorticoid Receptor Activation Leading to Increased Disease Susceptibility
982	Suppression, Suppression in mixed lymphocyte reaction (MLR)	Cellular	Nov 29, 2016	Dec 3, 2016
1203	Suppression, Suppression of production of cytotoxic T-cells	Tissue	Nov 29, 2016	Dec 3, 2016
1204	Suppression, Suppression of T-cell dependent antibody production	Cellular	Nov 29, 2016	Dec 3, 2016
983	Suppression, Suppression of T-cell dependent antibody response (TDAR)	Cellular	Nov 29, 2016	Dec 3, 2016
450	Suppression, VLDL secretion	Cellular	Nov 29, 2016	Sep 16, 2017	AhR activation leading to hepatic steatosis
1870	Sustentacular cells, decrease	Cellular	Apr 25, 2021	Mar 30, 2022	SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)
1944	Synaptic dysfunction	Organ	Oct 26, 2021	Jan 4, 2023	A cholesterol/glucose dysmetabolism initiated Tau-driven AOP toward memory loss (AO) in sporadic Alzheimer's Disease with plausible MIE's plug-ins for environmental neurotoxicants Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons Various neuronal effects induced by elavl3, sox10, and mbp
89	Synthesis, De Novo Fatty Acid (FA)	Cellular	Nov 29, 2016	Mar 29, 2024	LXR activation leading to hepatic steatosis Liver X Receptor (LXR) activation leads to liver steatosis
1439	Systemic acute phase response	Organ	Jun 29, 2017	Dec 18, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
486	systemic inflammation leading to hepatic steatosis	Organ	Nov 29, 2016	Feb 24, 2017	AKT2 activation leading to hepatic steatosis
1844	systemic inflammatory response syndrome	Individual	Mar 19, 2021	Mar 19, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation
1589	Systemic or topical administration of chemicals	Molecular	Feb 3, 2019	Feb 3, 2019
1506	Testicular atrophy	Organ	Jan 21, 2018	Jul 1, 2021	Histone deacetylase inhibition leading to testicular atrophy
1839	Testicular Cancer	Organ	Feb 12, 2021	Feb 12, 2021	Androgen receptor antagonism leading to testicular cancer
1704	testJF	Molecular	Dec 5, 2019	Dec 5, 2019
1708	Th17 cell migration and inflammation induction	Cellular	Dec 27, 2019	Nov 23, 2020	Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin disease Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
974	The binding of FK506 with FKBP12,		Nov 29, 2016	Nov 29, 2016
975	The binding of FK506 with FKBP12, The binding of FK506 with FKBP12		Nov 29, 2016	Nov 29, 2016
2240	The NO synthase pathway activation	Cellular	Jul 9, 2024	Jul 9, 2024	Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways
1462	Thiol group of chemicals interact with sulfuhydryl groups of proteins to form thiol adducts	Molecular	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
1916	Thromboinflammation, Increased	Organ	Aug 4, 2021	Aug 4, 2021	Endothelial cell dysfunction leading to thromboinflammation
1846	Thrombosis and Disseminated Intravascular Coagulation	Individual	Mar 25, 2021	Nov 25, 2022	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on pericytes leads to disseminated intravascular coagulation resulting in cerebrovascular disease (stroke) Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
277	Thyroid hormone synthesis, Decreased	Cellular	Nov 29, 2016	Nov 4, 2022	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Kidney dysfunction by decreased thyroid hormone Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to altered amphibian metamorphosis Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis Pendrin inhibition leading to altered amphibian metamorphosis Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis Inhibition of thyroid peroxidase leading to impaired fertility in fish Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse) Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
279	Thyroperoxidase, Inhibition	Molecular	Nov 29, 2016	Nov 4, 2022	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse) Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation Thyroperoxidase inhibition leading to altered amphibian metamorphosis Inhibition of thyroid peroxidase leading to impaired fertility in fish Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure Thyroperoxidase inhibition leading to altered visual function via decreased eye size Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning Thyroid peroxidase (TPO) inhibition leads to periventricular heterotopia formation in the developing rat brain
280	Thyroxine (T4) in neuronal tissue, Decreased	Organ	Nov 29, 2016	Apr 4, 2019	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals
1492	Tissue resident cell activation	Cellular	Nov 28, 2017	Jul 26, 2024	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 Protein Alkylation leading to Liver Fibrosis Increased DNA damage leading to increased risk of breast cancer Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer Deposition of Energy Leading to Learning and Memory Impairment
1848	Toll Like Receptor (TLR) Dysregulation	Molecular	Mar 26, 2021	Nov 23, 2021	Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS) Dysregulated underperforming Toll Like Receptors (TLRs) leading to high pathogen load Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality
1792	Toll-like receptor 4 activation	Molecular	Jul 9, 2020	Jul 9, 2020	Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis
1963	Torsades de Pointes	Organ	Dec 13, 2021	Jan 29, 2023	hERG channel blockade leading to sudden cardiac death
1438	Transcription of genes encoding acute phase proteins, Increased	Organ	Jun 29, 2017	Dec 18, 2023	Substance interaction with lung resident cell membrane components leading to atherosclerosis
1970	transposition of the great arteries	Organ	Feb 8, 2022	Feb 15, 2022	Inhibition of RALDH2 causes reduced all-trans retinoic acid levels, leading to transposition of the great arteries
1354	Treat, carbamazepine	Molecular	Apr 14, 2017	Apr 14, 2017	Molecular events lead to epilepsy presynaptic neuron 1 activation to epilepsy
1651	Treatment-resistant gastric cancer	Tissue	May 29, 2019	Oct 13, 2022	Increases in cellular reactive oxygen species and chronic reactive oxygen species leading to human treatment-resistant gastric cancer
1223	Trigeminal and/or vagal nerve excitation causes Airway Hyper-responsiveness,Cough, Dyspnea	Tissue	Nov 29, 2016	Sep 24, 2018	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1220	Trigeminal nerve activation	Tissue	Nov 29, 2016	Sep 24, 2018	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1229	TRPA1 activation, Chemical covalent binding to sulfhydyl group on TRPA1 receptor protein/ HEK293 fibroblast cells		Nov 29, 2016	Nov 29, 2016
1227	TRPA1 activation, Chemical covalent binding to sulfhydyl group on TRPA1 receptor protein/NEK293 fibroblast cells		Nov 29, 2016	Nov 29, 2016
1228	TRPA1 activation, Classic receptor binding / HEK 293 cells (fibroclast), cho cells (ovary), noncovalently linkked)		Nov 29, 2016	Nov 29, 2016
1215	TRPA1 activation, TRPA1 Receptor	Molecular	Nov 29, 2016	Sep 16, 2017	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation
1230	TRPV1 activation, TRPV1	Molecular	Nov 29, 2016	Dec 3, 2016
1720	Trypsin inhibition	Molecular	Jan 8, 2020	Jan 8, 2020	Trypsin inhibition leading to pancreatic acinar cell tumors
378	Tumorigenesis, Hepatocellular carcinoma	Individual	Nov 29, 2016	Nov 29, 2016	AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma (HCC)
1624	Tyrosinase inhibition leads to L-Dopaquinone reduction	Molecular	May 3, 2019	May 3, 2019
1150	Uncarboxylated osteocalcin not incorporated into bone matrix, decreasing bone strength, Impaired function of osteocalcin and MGP		Nov 29, 2016	Nov 29, 2016
1138	Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP	Molecular	Nov 29, 2016	Sep 16, 2017	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1120	Under carboxylated clotting factors will not assemble on cell surfaces , Failure to form clot		Nov 29, 2016	Nov 29, 2016
1122	Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis	Tissue	Nov 29, 2016	Dec 3, 2016	Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
1137	Under carboxylation of osteocalcin, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone		Nov 29, 2016	Nov 29, 2016
1168	Undercarboxylation of osteocalcin , Affects bone formation (osteoblast-osteoclast interaction, bone resorption) and glucose and lipid hoemostasis		Nov 29, 2016	Nov 29, 2016
1512	Unfolded Protein Response	Molecular	Apr 4, 2018	Sep 14, 2023	CYP2E1 activation and formation of protein adducts leading to neurodegeneration Inhibition of N-linked glycosylation leads to liver injury Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
1113	Unknown,		Nov 29, 2016	Nov 29, 2016
1114	Unknown, MIE	Molecular	Nov 29, 2016	Dec 3, 2016	unknown MIE leading to renal failure and mortality Unknown MIE altering cholesterol metabolism leading to decreased cognition
1129	Unresolved blood loss (hemorrhage), Failure in vascular repair mechanisms		Nov 29, 2016	Nov 29, 2016
1126	Unresolved blood loss, Failure in vascular repair mechanisms		Nov 29, 2016	Nov 29, 2016
1128	Unresolved hemorrhage, Failure in vascular repair mechanisms		Nov 29, 2016	Nov 29, 2016
470	Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1)	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis
54	Up Regulation, CD36	Molecular	Nov 29, 2016	Mar 26, 2024	LXR activation leading to hepatic steatosis NR1I3 (CAR) suppression leading to hepatic steatosis AhR activation leading to hepatic steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis Pregnane X Receptor (PXR) activation leads to liver steatosis
80	Up Regulation, CYP1A1	Molecular	Nov 29, 2016	Sep 16, 2017	AhR activation leading to hepatic steatosis AhR activation leading to liver fibrosis
84	Up Regulation, CYP1B1	Molecular	Nov 29, 2016	Dec 3, 2016
463	Up Regulation, FAS	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis
466	Up Regulation, LDLR (low density lipoprotein receptor)	Molecular	Nov 29, 2016	Sep 16, 2017	AhR activation leading to hepatic steatosis
462	Up Regulation, SCD-1	Molecular	Nov 29, 2016	Sep 16, 2017	NR1I3 (CAR) suppression leading to hepatic steatosis NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis AhR activation leading to hepatic steatosis G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
1284	Up Regulation, SREBF2	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP G protein-coupled estrogen receptor 1 (GPER) signal pathway in the lipid metabolism disrupting effects
276	Up Regulation, TGFbeta1 expression	Cellular	Nov 29, 2016	Sep 16, 2017
1285	Up Regulation, Unsaturated fatty acid	Cellular	Feb 15, 2017	Sep 16, 2017	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP
695	Upregulated, Spindle assembly checkpoint protein Mad2-oocyte	Molecular	Nov 29, 2016	Sep 16, 2017	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint
369	Uroporphyria	Individual	Nov 29, 2016	May 7, 2018	Aryl hydrocarbon receptor activation leading to uroporphyria
1762	Urothelial cell injury/death	Cellular	Apr 21, 2020	Apr 21, 2020	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
1763	Urothelial Tumor	Organ	Apr 21, 2020	Apr 21, 2020	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment
2154	Uterine adenocarcinoma (endometrioid adenocarcinoma Type I)	Organ	Jul 27, 2023	Jul 27, 2023	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation
2178	Vascular barrier disruption	Tissue	Aug 21, 2023	Aug 21, 2023	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects
2000	Vascular calcification	Organ	Apr 21, 2022	Apr 21, 2022
2003	Vascular remodeling	Organ	Apr 22, 2022	Apr 22, 2022
2002	Ventricular remodeling	Organ	Apr 22, 2022	Apr 22, 2022
2032	Viable offspring, decreased	Individual	Jul 18, 2022	Jul 18, 2022
1939	Viral infection and host-to-host transmission, proliferated	Individual	Oct 24, 2021	Jun 29, 2024	Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
1165	Vitamin K inhibition, gamma-carboxylation of glutamate to Gla residues reduced in bone proteins e.g., periostin		Nov 29, 2016	Nov 29, 2016
1111	weaj,		Nov 29, 2016	Nov 29, 2016
1465	Weak collagen matrix	Tissue	Aug 3, 2017	Aug 3, 2017	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity
2062	Weak, Procuticle protection	Organ	Aug 28, 2022	Aug 28, 2022	Knickkopf leading to mortality
1107	Weakened, Colony	Population	Nov 29, 2016	Jun 7, 2018	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1 Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure Nicotinic acetylcholine receptor activation contributes to mitochondrial dysfunction and leads to colony loss/failure Varroa mite infestation increases virus levels leading to colony loss/failure Varroa mite infestation contributes to abnormal foraging leading to colony loss/failure Weather event contributes to colony loss/failure Weather event contributes abnormal foraging leading to colony loss/failure Nosema infection increases energetic demands leading to colony loss/failure Nosema infection causes abnormal role change that leads to colony loss/failure Queen egg-laying decrease leads to colony loss/failure
1645	Wnt ligand stimulation	Molecular	May 28, 2019	May 29, 2019
1648	β-catenin activation	Molecular	May 29, 2019	May 29, 2019