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Lead

Associated High Confidence AOPs

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Associated AOPs with Level of Relevance 1
AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:3	Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits	Nervous System Disease	WPHA/WNT Endorsed	0.29	KE:177	Mitochondrial dysfunction
AOP:3		Nervous System Disease	WPHA/WNT Endorsed	0.29	KE:188	Neuroinflammation
AOP:4	Ecdysone receptor agonism leading to incomplete ecdysis associated mortality	Unclassified	-	0.3	KE:1264	Increase, Nuclear receptor E75b gene expression
					KE:993	Decrease, Abdominal muscle contraction
					KE:1265	Increase, Fushi tarazu factor-1 gene expression
AOP:7	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female	Reproductive System Disease; Endocrine System Disease; Reproductive System Disease	Under Review	0.4	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:7			Under Review	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous System Disease	Under Development	0.22	KE:758	Hippocampal Physiology, Altered
AOP:8		Nervous System Disease	Under Development	0.22	KE:756	Hippocampal gene expression, Altered
AOP:10	Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain	Nervous System Disease	WPHA/WNT Endorsed	0.17	KE:669	Reduction, Neuronal synaptic inhibition
AOP:15	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations	Genetic Disease	WPHA/WNT Endorsed	0.25	KE:155	Inadequate DNA repair
AOP:16	Acetylcholinesterase inhibition leading to acute mortality	Unclassified	Under Development	0.14	KE:445	Respiratory distress/arrest
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive System Disease	Under Review	0.38	KE:413	Reduction, Testosterone synthesis in Leydig cells
					KE:1690	Decrease, circulating testosterone levels
					KE:289	Decrease, Translocator protein (TSPO)
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	0.3	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:285	Reduction, Vitellogenin synthesis in liver
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	0.38	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:285	Reduction, Vitellogenin synthesis in liver
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal System Disease	Under Development	0.38	KE:149	Increase, Inflammation
					KE:1115	Increase, Reactive oxygen species
					KE:288	Activation of specific nuclear receptors, Transcriptional change
AOP:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	0.17	KE:285	Reduction, Vitellogenin synthesis in liver
AOP:36	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.12	KE:140	Decreased, HSD17B10 expression
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal System Disease	Under Development	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal System Disease	WPHA/WNT Endorsed	0.29	KE:1493	Increased Pro-inflammatory mediators
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal System Disease	WPHA/WNT Endorsed	0.29	KE:55	Increase, Cell injury/death
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal System Disease	Under Review	0.6	KE:854	Alterations, Cellular proliferation / hyperplasia
					KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
					KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.25	KE:462	Up Regulation, SCD-1
					KE:454	Increased, Triglyceride formation
					KE:463	Up Regulation, FAS
					KE:54	Up Regulation, CD36
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.42	KE:454	Increased, Triglyceride formation
					KE:54	Up Regulation, CD36
					KE:462	Up Regulation, SCD-1
					KE:474	Down Regulation, HMGCS2
					KE:472	Down Regulation, CPT1A
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive System Disease	-	0.57	KE:413	Reduction, Testosterone synthesis in Leydig cells
					KE:1690	Decrease, circulating testosterone levels
					KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
					KE:520	Decreased sperm quantity or quality in the adult, Decreased fertility
AOP:73	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity	Unclassified	-	0.15	KE:10059	Decreased LH surge for 24 hours
AOP:73		Unclassified	-	0.15	KE:531	Decreased, LH Surge
AOP:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	0.29	KE:177	Mitochondrial dysfunction
AOP:77		Unclassified	-	0.29	KE:341	Impairment, Learning and memory
AOP:78	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1	Unclassified	-	0.25	KE:177	Mitochondrial dysfunction
AOP:78		Unclassified	-	0.25	KE:341	Impairment, Learning and memory
AOP:79	Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failure	Unclassified	-	0.2	KE:177	Mitochondrial dysfunction
AOP:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	0.25	KE:177	Mitochondrial dysfunction
AOP:80		Unclassified	-	0.25	KE:664	Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	0.25	KE:177	Mitochondrial dysfunction
AOP:87		Unclassified	-	0.25	KE:341	Impairment, Learning and memory
AOP:88	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste	Unclassified	-	0.14	KE:341	Impairment, Learning and memory
AOP:89	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure	Unclassified	-	0.12	KE:341	Impairment, Learning and memory
AOP:90	Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2	Unclassified	-	0.12	KE:341	Impairment, Learning and memory
AOP:94	Sodium channel inhibition leading to congenital malformations	Unclassified	-	0.17	KE:445	Respiratory distress/arrest
AOP:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	0.33	KE:602	Increased, Ataxia, paralysis, or hyperactivity
AOP:96	Axonal sodium channel modulation leading to acute mortality	Unclassified	-	0.33	KE:600	Overactivation, Neuronotransmitter release
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive System Disease	-	0.2	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:102		Reproductive System Disease	-	0.2	KE:693	Increased, cyclic adenosine monophosphate
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive System Disease	-	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:104	Altered ion channel activity leading impaired heart function	Unclassified	-	0.25	KE:698	Altered, Action Potential
AOP:107	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Cancer; Gastrointestinal System Disease	Under Review	0.4	KE:1214	Altered gene expression specific to CAR activation, Hepatocytes
AOP:107		Cancer; Gastrointestinal System Disease	Under Review	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP:108	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.17	KE:768	Increase, Cytotoxicity
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory System Disease	-	0.2	KE:734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:110		Cancer; Endocrine System Disease	-	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:111	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)	Cancer; Reproductive System Disease	-	0.2	KE:754	Increased, Luteinizing hormone (LH)
AOP:113	Glutamate-gated chloride channel activation leading to acute mortality	Unclassified	-	0.17	KE:764	N/A, Ataxia, paralysis, or hyperactivity
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	0.33	KE:777	Increase, Inflammation (corneal cells)
AOP:114		Cancer	-	0.33	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	0.4	KE:149	Increase, Inflammation
AOP:115		Cancer	-	0.4	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	Under Development	0.25	KE:716	Increase, cell proliferation (hepatocytes)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:119		Cancer; Endocrine System Disease	-	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:120	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)	Cancer; Reproductive System Disease	-	0.4	KE:1690	Decrease, circulating testosterone levels
AOP:120		Cancer; Reproductive System Disease	-	0.4	KE:791	Increased, Leutinizing hormone (LH)
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	0.4	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:799	Increased, HIF-1 heterodimer
					KE:285	Reduction, Vitellogenin synthesis in liver
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	0.45	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:802	Increased, HIF-1 alpha transcription
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
					KE:285	Reduction, Vitellogenin synthesis in liver
					KE:799	Increased, HIF-1 heterodimer
AOP:126	Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation	Unclassified	-	0.15	KE:10059	Decreased LH surge for 24 hours
AOP:126		Unclassified	-	0.15	KE:531	Decreased, LH Surge
AOP:130	Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity	Gastrointestinal System Disease	Under Development	0.09	KE:177	Mitochondrial dysfunction
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign Neoplasm; Respiratory System Disease	Under Review	0.29	KE:768	Increase, Cytotoxicity
AOP:136		Benign Neoplasm; Respiratory System Disease	Under Review	0.29	KE:870	Increase, Cell Proliferation
AOP:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal System Disease	Under Review	0.33	KE:177	Mitochondrial dysfunction
					KE:1493	Increased Pro-inflammatory mediators
					KE:55	Increase, Cell injury/death
AOP:148	EGFR Activation Leading to Decreased Lung Function	Respiratory System Disease	Under Development	0.25	KE:962	Increase, Mucin production
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.12	KE:277	Thyroid hormone synthesis, Decreased
AOP:160	Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality	Unclassified	-	0.14	KE:1015	Increased, Neuronal synaptic inhibition
AOP:161	Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality	Unclassified	-	0.14	KE:1015	Increased, Neuronal synaptic inhibition
AOP:164	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse	Cancer; Reproductive System Disease	-	0.17	KE:1042	Proliferation/Clonal Expansion, smooth muscle
AOP:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive System Disease; Cancer	-	0.29	KE:1066	Promotion, SIX-1 postive basal-type progenitor cells
AOP:167		Reproductive System Disease; Cancer	-	0.29	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:173	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis	Musculoskeletal System Disease; Respiratory System Disease	WPHA/WNT Endorsed	0.25	KE:1497	Increased, recruitment of inflammatory cells
AOP:173		Musculoskeletal System Disease; Respiratory System Disease	WPHA/WNT Endorsed	0.25	KE:1496	Increased, secretion of proinflammatory mediators
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.17	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:191	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:201	Juvenile hormone receptor agonism leading to male offspring induction associated population decline	Unclassified	-	0.17	KE:1206	Induction, Doublesex1 gene
AOP:206	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis	Musculoskeletal System Disease; Respiratory System Disease	Under Development	0.17	KE:149	Increase, Inflammation
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive System Disease	-	0.5	KE:1115	Increase, Reactive oxygen species
					KE:177	Mitochondrial dysfunction
					KE:1262	Apoptosis
					KE:1281	Increased, DNA Damage-Repair
AOP:213	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:218	Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity	Unclassified	-	0.17	KE:1141	Decreased, Reproductive Success
AOP:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	0.33	KE:1141	Decreased, Reproductive Success
AOP:219		Unclassified	-	0.33	KE:1390	Sexual behavior, decreased
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP:271		Unclassified	Under Development	0.4	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural Tube Defect	-	0.2	KE:1239	Altered, Gene Expression
AOP:276	Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome	Urinary System Disease	-	0.17	KE:1562	Decreased Na/K ATPase activity
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-	0.12	KE:55	Increase, Cell injury/death
AOP:280	α-diketone-induced bronchiolitis obliterans	Musculoskeletal System Disease; Respiratory System Disease	-	0.14	KE:149	Increase, Inflammation
AOP:288	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)	Endocrine System Disease	-	0.12	KE:1690	Decrease, circulating testosterone levels
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.22	KE:1493	Increased Pro-inflammatory mediators
AOP:293		Genetic Disease; Thoracic Disease; Cancer	Under Development	0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.22	KE:1493	Increased Pro-inflammatory mediators
AOP:294		Genetic Disease; Thoracic Disease; Cancer	Under Development	0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:297	Inhibition of retinaldehyde dehydrogenase leads to population decline	Unclassified	Under Development	0.17	KE:1643	Altered, Visual function
AOP:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-	0.14	KE:1115	Increase, Reactive oxygen species
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.25	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	0.25	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:285	Reduction, Vitellogenin synthesis in liver
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:311	Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis	Unclassified	-	0.14	KE:1115	Increase, Reactive oxygen species
AOP:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	0.22	KE:1750	Increased inflammatory immune responses
AOP:320		Unclassified	Under Development	0.22	KE:1496	Increased, secretion of proinflammatory mediators
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-	0.18	KE:592	Reduced, survival
AOP:321		Unclassified	-	0.18	KE:10042	Abnormal development
AOP:334	Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration	Unclassified	-	0.33	KE:2089	Altered Bone Cell Homeostasis
AOP:334		Unclassified	-	0.33	KE:2245	Altered Cell Differentiation Signaling
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development	0.25	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine System Disease; Reproductive System Disease; Reproductive System Disease	Under Development	0.17	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:346	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation	Unclassified	WPHA/WNT Endorsed	0.4	KE:1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:346		Unclassified	WPHA/WNT Endorsed	0.4	KE:1790	Increased, Differentiation to Testis
AOP:362	Immune mediated hepatitis	Gastrointestinal System Disease; Immune System Disease	-	0.12	KE:177	Mitochondrial dysfunction
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:363		Unclassified	Under Review	0.25	KE:1643	Altered, Visual function
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:364		Unclassified	Under Development	0.25	KE:1643	Altered, Visual function
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:365		Unclassified	Under Development	0.25	KE:1643	Altered, Visual function
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine System Disease; Reproductive System Disease; Cancer	-	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:374	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis	Nervous System Disease	Under Development	0.5	KE:188	Neuroinflammation
AOP:374		Nervous System Disease	Under Development	0.5	KE:352	N/A, Neurodegeneration
AOP:376	Androgen receptor agonism leading to male-biased sex ratio	Unclassified	WPHA/WNT Endorsed	0.25	KE:1790	Increased, Differentiation to Testis
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular System Disease	Under Development	0.14	KE:1869	Diminished protective oxidative stress response
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal System Disease; Respiratory System Disease	Under Development	0.33	KE:1115	Increase, Reactive oxygen species
AOP:382		Musculoskeletal System Disease; Respiratory System Disease	Under Development	0.33	KE:1496	Increased, secretion of proinflammatory mediators
AOP:383	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis	Gastrointestinal System Disease	Under Development	0.17	KE:1115	Increase, Reactive oxygen species
AOP:386	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis	Reproductive System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive System Disease	-	0.25	KE:40	Decrease, Mitochondrial ATP production
AOP:387		Reproductive System Disease	-	0.25	KE:1115	Increase, Reactive oxygen species
AOP:397	Bulky DNA adducts leading to mutations	Genetic Disease	Under Development	0.33	KE:155	Inadequate DNA repair
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	0.25	KE:1821	Decrease, Cell proliferation
AOP:399		Unclassified	-	0.25	KE:1643	Altered, Visual function
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.62	KE:870	Increase, Cell Proliferation
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
					KE:1896	Genomic instability
					KE:1497	Increased, recruitment of inflammatory cells
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	0.1	KE:1008	Reduced, Hearing
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:413		Unclassified	-	0.33	KE:759	Increased, Kidney Failure
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory System Disease	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory System Disease	-	0.25	KE:1262	Apoptosis
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic System Disease; Cancer	-	0.36	KE:155	Inadequate DNA repair
					KE:870	Increase, Cell Proliferation
					KE:1493	Increased Pro-inflammatory mediators
					KE:403	Suppression, Immune system
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.33	KE:149	Increase, Inflammation
					KE:1971	Increased, tumor growth
					KE:1262	Apoptosis
AOP:441	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation	Congenital Nervous System Abnormality; Nervous System Disease	-	0.14	KE:1262	Apoptosis
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic Disease; Cancer	Under Development	0.2	KE:1554	Increase Chromosomal Aberrations
AOP:443		Thoracic Disease; Cancer	Under Development	0.2	KE:155	Inadequate DNA repair
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.09	KE:1262	Apoptosis
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	0.33	KE:1821	Decrease, Cell proliferation
					KE:1262	Apoptosis
					KE:2040	Decrease, GLI1/2 target gene expression
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous System Disease	-	0.11	KE:177	Mitochondrial dysfunction
AOP:464		Nervous System Disease	-	0.11	KE:389	Increased, Intracellular Calcium overload
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.12	KE:2050	Increase, developmental abnormalities
AOP:467	Knickkopf leading to mortality	Unclassified	-	0.11	KE:2050	Increase, developmental abnormalities
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular System Disease	Under Review	0.12	KE:1493	Increased Pro-inflammatory mediators
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.3	KE:870	Increase, Cell Proliferation
					KE:155	Inadequate DNA repair
					KE:1636	Increase, Chromosomal aberrations
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular System Disease; Thoracic Disease	Under Development	0.43	KE:177	Mitochondrial dysfunction
					KE:55	Increase, Cell injury/death
					KE:1532	Decrease, Cardiac contractility
AOP:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular System Disease; Thoracic Disease	Under Development	0.6	KE:40	Decrease, Mitochondrial ATP production
					KE:177	Mitochondrial dysfunction
					KE:1532	Decrease, Cardiac contractility
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:2089	Altered Bone Cell Homeostasis
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:2245	Altered Cell Differentiation Signaling
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive System Disease	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.17	KE:55	Increase, Cell injury/death
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive System Disease; Cancer	-	0.33	KE:854	Alterations, Cellular proliferation / hyperplasia
					KE:1183	Decreased, Apoptosis (Epithelial Cells)
					KE:286	Altered, Transcription of genes by the androgen receptor
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	0.3	KE:1690	Decrease, circulating testosterone levels
					KE:286	Altered, Transcription of genes by the androgen receptor
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:503	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation	Reproductive System Disease; Cancer	Under Review	0.17	KE:1896	Genomic instability
AOP:517	Pregnane X Receptor (PXR) activation leads to liver steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.2	KE:54	Up Regulation, CD36
AOP:519	Cardiac ion channels blockade leading to increased incidence of cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.5	KE:1961	Prolongation of Action Potential Duration
AOP:519		Cardiovascular System Disease	-	0.5	KE:2283	Increased the early premature depolarizations during repolarization
AOP:529	Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.12	KE:2224	Dysregulation of transcriptional expression within PPAR signaling network
AOP:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal System Disease	-	0.4	KE:177	Mitochondrial dysfunction
AOP:530		Gastrointestinal System Disease	-	0.4	KE:55	Increase, Cell injury/death
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-	0.17	KE:307	Increase, Vitellogenin synthesis in liver
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-	0.2	KE:307	Increase, Vitellogenin synthesis in liver
AOP:544	Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation	Nervous System Disease	-	0.17	KE:149	Increase, Inflammation
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-	0.12	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive System Disease; Endocrine System Disease	-	0.17	KE:1262	Apoptosis
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	0.18	KE:40	Decrease, Mitochondrial ATP production
AOP:564		Unclassified	-	0.18	KE:2151	Disruption, neurotransmitter release

Associated AOPs with Level of Relevance 2
AOPs with at least 1 AO associated with chemical, and no associated MIE

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed	0.12	KE:864	Decreased, Body Weight
AOP:17	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	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.4	KE:55	Increase, Cell injury/death
					KE:1493	Increased Pro-inflammatory mediators
					KE:188	Neuroinflammation
					KE:341	Impairment, Learning and memory
AOP:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive System Disease	-	0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:19		Reproductive System Disease	-	0.4	KE:337	N/A, Impairment of reproductive capacity
AOP:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	0.6	KE:317	Altered, Cardiovascular development/function
					KE:1269	Increase, COX-2 expression
					KE:947	Increase, Early Life Stage Mortality
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.31	KE:177	Mitochondrial dysfunction
					KE:54	Up Regulation, CD36
					KE:258	Activation, SCD-1
					KE:345	N/A, Liver Steatosis
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	WPHA/WNT Endorsed	0.5	KE:277	Thyroid hormone synthesis, Decreased
					KE:758	Hippocampal Physiology, Altered
					KE:402	Cognitive function, decreased
					KE:756	Hippocampal gene expression, Altered
AOP:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	0.2	KE:1001	Increased, Developmental Defects
AOP:48	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.67	KE:389	Increased, Intracellular Calcium overload
					KE:177	Mitochondrial dysfunction
					KE:188	Neuroinflammation
					KE:55	Increase, Cell injury/death
					KE:352	N/A, Neurodegeneration
					KE:341	Impairment, Learning and memory
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.3	KE:277	Thyroid hormone synthesis, Decreased
					KE:341	Impairment, Learning and memory
					KE:381	Reduced levels of BDNF
AOP:91	Sodium channel inhibition leading to reduced survival	Unclassified	-	0.17	KE:592	Reduced, survival
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	0.29	KE:636	Decreased, survival
AOP:99		Unclassified	-	0.29	KE:341	Impairment, Learning and memory
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary System Disease	-	0.33	KE:713	Increase, Adenomas/carcinomas (renal tubular)
AOP:105		Cancer; Urinary System Disease	-	0.33	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary System Disease	-	0.5	KE:713	Increase, Adenomas/carcinomas (renal tubular)
AOP:116		Cancer; Urinary System Disease	-	0.5	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive System Disease	-	0.5	KE:330	Decrease, Fertility
					KE:1690	Decrease, circulating testosterone levels
					KE:807	Decreased, cholesterol
AOP:131	Aryl hydrocarbon receptor activation leading to uroporphyria	Inherited Metabolic Disorder	WPHA/WNT Endorsed	0.33	KE:369	Uroporphyria
AOP:131		Inherited Metabolic Disorder	WPHA/WNT Endorsed	0.33	KE:850	Induction, CYP1A2/CYP1A5
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.44	KE:277	Thyroid hormone synthesis, Decreased
					KE:758	Hippocampal Physiology, Altered
					KE:402	Cognitive function, decreased
					KE:756	Hippocampal gene expression, Altered
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.5	KE:885	Increase, Cancer
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.5	KE:155	Inadequate DNA repair
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular System Disease	Under Development	0.1	KE:952	Hypertension
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	0.43	KE:317	Altered, Cardiovascular development/function
					KE:947	Increase, Early Life Stage Mortality
					KE:948	reduced production, VEGF
AOP:151	AhR activation leading to preeclampsia	Cardiovascular System Disease	Under Development	0.29	KE:1893	increase, Preeclampsia
AOP:151	AhR activation leading to preeclampsia	Cardiovascular System Disease	Under Development	0.29	KE:948	reduced production, VEGF
AOP:196	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation	Respiratory System Disease	-	0.11	KE:1226	Increased Respiratory irritability and Chronic Cough,
AOP:203	5-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population decline	Reproductive System Disease	-	0.12	KE:1141	Decreased, Reproductive Success
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1506	Testicular atrophy
AOP:212		Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1262	Apoptosis
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal System Disease	WPHA/WNT Endorsed	0.6	KE:1393	Hepatocytotoxicity
					KE:1394	Induction, persistent proliferation/sustained proliferation
					KE:1395	Liver Cancer
AOP:237	Substance interaction with lung resident cell membrane components leading to atherosclerosis	Cardiovascular System Disease	Under Development	0.4	KE:1443	Atherosclerosis
AOP:237		Cardiovascular System Disease	Under Development	0.4	KE:1496	Increased, secretion of proinflammatory mediators
AOP:242	Inhibition of lysyl oxidase leading to enhanced chronic fish toxicity	Unclassified	-	0.12	KE:636	Decreased, survival
AOP:245	Reduction in photophosphorylation leading to growth inhibition in aquatic plants	Unclassified	-	0.18	KE:40	Decrease, Mitochondrial ATP production
AOP:245		Unclassified	-	0.18	KE:1521	Decrease, Growth
AOP:256	Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicity	Urinary System Disease	Under Development	0.4	KE:177	Mitochondrial dysfunction
AOP:256		Urinary System Disease	Under Development	0.4	KE:814	Occurrence, Kidney toxicity
AOP:257	Receptor mediated endocytosis and lysosomal overload leading to kidney toxicity	Urinary System Disease	Under Development	0.2	KE:814	Occurrence, Kidney toxicity
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary System Disease	Under Development	0.6	KE:40	Decrease, Mitochondrial ATP production
					KE:177	Mitochondrial dysfunction
					KE:814	Occurrence, Kidney toxicity
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous System Disease	-	0.14	KE:1514	Neurodegeneration
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-	0.17	KE:10013	Impaired growth and development
AOP:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-	0.12	KE:10016	Impaired locomotor activity
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.57	KE:870	Increase, Cell Proliferation
					KE:1556	Increase, lung cancer
					KE:155	Inadequate DNA repair
					KE:1636	Increase, Chromosomal aberrations
AOP:274	Histone deacetylase inhibition leads to impeded craniofacial development	Musculoskeletal System Disease	-	0.25	KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
AOP:279	Microtubule interacting drugs lead to peripheral neuropathy	Nervous System Disease	-	0.25	KE:1583	Sensory axonal peripheral neuropathy
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous System Disease	-	0.4	KE:389	Increased, Intracellular Calcium overload
					KE:55	Increase, Cell injury/death
					KE:352	N/A, Neurodegeneration
					KE:1350	Increased, glutamate
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	0.75	KE:1821	Decrease, Cell proliferation
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1521	Decrease, Growth
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:287		Unclassified	-	0.5	KE:1521	Decrease, Growth
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	0.75	KE:1821	Decrease, Cell proliferation
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1521	Decrease, Growth
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:291		Unclassified	-	0.5	KE:1521	Decrease, Growth
AOP:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic Disease; Chromosomal Disease	WPHA/WNT Endorsed	0.4	KE:155	Inadequate DNA repair
AOP:296		Genetic Disease; Chromosomal Disease	WPHA/WNT Endorsed	0.4	KE:1636	Increase, Chromosomal aberrations
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	Under Development	0.6	KE:758	Hippocampal Physiology, Altered
					KE:402	Cognitive function, decreased
					KE:756	Hippocampal gene expression, Altered
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.57	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1670	Lung cancer
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.4	KE:1757	Reduce, Sperm count
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.4	KE:155	Inadequate DNA repair
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	0.33	KE:2147	Decreased, Viable Offspring
AOP:323		Unclassified	-	0.33	KE:807	Decreased, cholesterol
AOP:384	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease	Urinary System Disease	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:384		Urinary System Disease	-	0.33	KE:1603	Chronic kidney disease
AOP:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	0.6	KE:1868	Hyperinflammation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:405	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function	Cognitive Disorder	-	0.2	KE:402	Cognitive function, decreased
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-	0.33	KE:1868	Hyperinflammation
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-	0.33	KE:1869	Diminished protective oxidative stress response
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:416		Cancer	-	0.33	KE:1670	Lung cancer
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-	0.2	KE:1670	Lung cancer
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-	0.5	KE:870	Increase, Cell Proliferation
AOP:420		Cancer	-	0.5	KE:1670	Lung cancer
AOP:431	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)	Inherited Metabolic Disorder	-	0.4	KE:1953	Gestational diabetes mellitus
AOP:431		Inherited Metabolic Disorder	-	0.4	KE:1952	Abnormal, Glucose homeostasis
AOP:433	hERG channel blockade leading to sudden cardiac death	Cardiovascular System Disease	-	0.67	KE:1961	Prolongation of Action Potential Duration
					KE:1962	Prolongation of QT interval
					KE:1963	Torsades de Pointes
					KE:1964	Sudden cardiac death
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary System Disease	Under Development	0.4	KE:177	Mitochondrial dysfunction
AOP:437		Urinary System Disease	Under Development	0.4	KE:814	Occurrence, Kidney toxicity
AOP:442	Binding to voltage gate sodium channels during development leads to cognitive impairment	Cognitive Disorder	Under Review	0.29	KE:758	Hippocampal Physiology, Altered
AOP:442		Cognitive Disorder	Under Review	0.29	KE:402	Cognitive function, decreased
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous System Disease	-	0.29	KE:1583	Sensory axonal peripheral neuropathy
AOP:450		Nervous System Disease	-	0.29	KE:352	N/A, Neurodegeneration
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.56	KE:870	Increase, Cell Proliferation
					KE:1670	Lung cancer
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
					KE:1497	Increased, recruitment of inflammatory cells
AOP:455	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development	Musculoskeletal System Disease	Under Review	0.67	KE:2020	Decrease, sox9 expression
					KE:947	Increase, Early Life Stage Mortality
					KE:2021	Increase, slincR expression
					KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	0.67	KE:2020	Decrease, sox9 expression
					KE:317	Altered, Cardiovascular development/function
					KE:947	Increase, Early Life Stage Mortality
					KE:2021	Increase, slincR expression
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited Metabolic Disorder	-	0.33	KE:277	Thyroid hormone synthesis, Decreased
AOP:457		Inherited Metabolic Disorder	-	0.33	KE:2119	Insulin resistance, increased
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.38	KE:758	Hippocampal Physiology, Altered
					KE:402	Cognitive function, decreased
					KE:756	Hippocampal gene expression, Altered
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.56	KE:758	Hippocampal Physiology, Altered
					KE:850	Induction, CYP1A2/CYP1A5
					KE:402	Cognitive function, decreased
					KE:277	Thyroid hormone synthesis, Decreased
					KE:756	Hippocampal gene expression, Altered
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-	0.38	KE:1868	Hyperinflammation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	0.2	KE:885	Increase, Cancer
AOP:475	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons	Developmental Disorder Of Mental Health	Under Development	0.25	KE:389	Increased, Intracellular Calcium overload
AOP:475		Developmental Disorder Of Mental Health	Under Development	0.25	KE:341	Impairment, Learning and memory
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental Disorder Of Mental Health	Under Review	0.12	KE:341	Impairment, Learning and memory
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive Disorder	-	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive Disorder	-	0.14	KE:402	Cognitive function, decreased
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental Disorder Of Mental Health	-	0.55	KE:2121	decreased, Intellectual Quotient
					KE:758	Hippocampal Physiology, Altered
					KE:188	Neuroinflammation
					KE:1350	Increased, glutamate
					KE:55	Increase, Cell injury/death
					KE:341	Impairment, Learning and memory
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired Metabolic Disease	-	0.4	KE:2129	Metabolically unhealthy Obesity
					KE:1497	Increased, recruitment of inflammatory cells
					KE:2125	Increased fat mass
					KE:2119	Insulin resistance, increased
AOP:497	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome	Inherited Metabolic Disorder; Disease Of Metabolism	-	0.5	KE:1115	Increase, Reactive oxygen species
					KE:177	Mitochondrial dysfunction
					KE:2145	Metabolic syndrome
					KE:2119	Insulin resistance, increased
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous System Disease	-	0.5	KE:191	Neuronal dysfunction
AOP:498		Nervous System Disease	-	0.5	KE:2150	Neurological disorder
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous System Disease	-	0.25	KE:2150	Neurological disorder
AOP:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular System Disease	-	0.17	KE:2161	Increase, Vascular disrupting effects
AOP:508	Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathway	Cardiovascular System Disease	-	0.14	KE:2161	Increase, Vascular disrupting effects
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular System Disease	-	0.29	KE:177	Mitochondrial dysfunction
AOP:509		Cardiovascular System Disease	-	0.29	KE:2161	Increase, Vascular disrupting effects
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular System Disease	-	0.1	KE:2161	Increase, Vascular disrupting effects
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.4	KE:2204	Altered brain morphology
AOP:520		Developmental Disorder Of Mental Health	-	0.4	KE:341	Impairment, Learning and memory
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	0.43	KE:1115	Increase, Reactive oxygen species
					KE:2147	Decreased, Viable Offspring
					KE:2206	Increased, histomorphological alteration of testis
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.08	KE:341	Impairment, Learning and memory
AOP:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-	0.2	KE:2231	Locomotor function. Impaired
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.33	KE:341	Impairment, Learning and memory
AOP:533		Developmental Disorder Of Mental Health	-	0.33	KE:1239	Altered, Gene Expression
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	0.5	KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental Disorder Of Mental Health	-	0.56	KE:389	Increased, Intracellular Calcium overload
					KE:1262	Apoptosis
					KE:188	Neuroinflammation
					KE:341	Impairment, Learning and memory
					KE:2151	Disruption, neurotransmitter release
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	0.2	KE:885	Increase, Cancer
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular System Disease	-	0.2	KE:1535	Heart failure
AOP:551	Increased Muscarinic M2 Receptor leading to Arrhythmia	Symptom	-	0.2	KE:1106	Occurrence, cardiac arrhythmia
AOP:553	Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure	Cardiovascular System Disease	-	0.75	KE:698	Altered, Action Potential
					KE:1532	Decrease, Cardiac contractility
					KE:1535	Heart failure
AOP:554	β-adrenergic receptor agonists leading to arrhythmias.	Symptom	-	0.25	KE:1106	Occurrence, cardiac arrhythmia
AOP:559	Inhibition of acetylcholinesterase (AChE) leading to arrhythmias	Symptom	-	0.4	KE:698	Altered, Action Potential
AOP:559		Symptom	-	0.4	KE:1106	Occurrence, cardiac arrhythmia
AOP:562	HCN Channel Inhibition leading to Arrhythmias	Symptom	-	0.6	KE:1106	Occurrence, cardiac arrhythmia
					KE:2291	Slowed Heart Rate
					KE:2292	Altered Cardiac Electrical Conduction
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental Disorder Of Mental Health	-	0.5	KE:2121	decreased, Intellectual Quotient
					KE:1115	Increase, Reactive oxygen species
					KE:2195	Increase, CNS Neural cell death

Associated AOPs with Level of Relevance 3
AOPs with at least 1 MIE associated with chemical, and no associated AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory System Disease	Under Development	0.6	KE:396	Covalent Binding, Protein
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:272	Activation/Proliferation, T-cells
AOP:62	AKT2 activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.25	KE:486	systemic inflammation leading to hepatic steatosis
AOP:69	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell	Reproductive System Disease	-	0.2	KE:642	Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive System Disease; Cancer	-	0.17	KE:746	Increase, Dopaminergic activity
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.5	KE:786	Increase, Cytotoxicity (hepatocytes)
AOP:118		Cancer; Gastrointestinal System Disease	-	0.5	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary System Disease	-	0.4	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:121		Cancer; Urinary System Disease	-	0.4	KE:793	Increase, Urinary bladder calculi
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal System Disease	-	0.38	KE:1287	Glutathione synthesis
					KE:1286	Down Regulation, GSS and GSTs gene
					KE:1284	Up Regulation, SREBF2
AOP:282	Adverse outcome pathway on photochemical toxicity initiated by light exposure	Unclassified	Under Review	0.25	KE:1115	Increase, Reactive oxygen species
AOP:298	Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROS	Cancer; Gastrointestinal System Disease	Under Review	0.33	KE:1115	Increase, Reactive oxygen species
AOP:298		Cancer; Gastrointestinal System Disease	Under Review	0.33	KE:1753	Chronic reactive oxygen species
AOP:327	Excessive reactive oxygen species production leading to mortality (1)	Unclassified	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:327		Unclassified	-	0.4	KE:1769	Increase, Body fluid overload
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:328		Unclassified	-	0.4	KE:1771	Decrease, Adenosine triphosphate pool
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:329		Unclassified	-	0.4	KE:1771	Decrease, Adenosine triphosphate pool
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary System Disease	-	0.4	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:335		Cancer; Urinary System Disease	-	0.4	KE:177	Mitochondrial dysfunction
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:423		Unclassified	-	0.33	KE:177	Mitochondrial dysfunction
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:438		Cardiovascular System Disease	-	0.17	KE:177	Mitochondrial dysfunction
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.35	KE:1262	Apoptosis
					KE:149	Increase, Inflammation
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
					KE:1239	Altered, Gene Expression
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1198	Activation, Macrophages
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.18	KE:1443	Atherosclerosis
					KE:1115	Increase, Reactive oxygen species
					KE:1198	Activation, Macrophages
AOP:453	Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population	Gastrointestinal System Disease	-	0.23	KE:1995	Abnormal lipid metabolism
					KE:1115	Increase, Reactive oxygen species
					KE:1198	Activation, Macrophages
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.36	KE:149	Increase, Inflammation
					KE:177	Mitochondrial dysfunction
					KE:1262	Apoptosis
					KE:1115	Increase, Reactive oxygen species
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal System Disease	-	0.23	KE:1995	Abnormal lipid metabolism
					KE:1115	Increase, Reactive oxygen species
					KE:1198	Activation, Macrophages
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	0.5	KE:1821	Decrease, Cell proliferation
					KE:1262	Apoptosis
					KE:2040	Decrease, GLI1/2 target gene expression
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-	0.44	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:285	Reduction, Vitellogenin synthesis in liver
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular System Disease	-	0.23	KE:1115	Increase, Reactive oxygen species
					KE:1493	Increased Pro-inflammatory mediators
					KE:1198	Activation, Macrophages

Associated AOPs with Level of Relevance 5
AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:12	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging	Nervous System Disease; Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	1.0	KE:195	Inhibition, NMDARs
					KE:188	Neuroinflammation
					KE:52	Decreased, Calcium influx
					KE:201	Binding of antagonist, NMDA receptors
					KE:341	Impairment, Learning and memory
					KE:352	N/A, Neurodegeneration
					KE:55	Increase, Cell injury/death
					KE:381	Reduced levels of BDNF
AOP:13	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.6	KE:195	Inhibition, NMDARs
					KE:52	Decreased, Calcium influx
					KE:201	Binding of antagonist, NMDA receptors
					KE:341	Impairment, Learning and memory
					KE:55	Increase, Cell injury/death
					KE:381	Reduced levels of BDNF
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary System Disease	WPHA/WNT Endorsed	0.8	KE:827	sensitisation, skin
					KE:826	Activation, Keratinocytes
					KE:396	Covalent Binding, Protein
					KE:272	Activation/Proliferation, T-cells
AOP:95	Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival	Unclassified	-	0.33	KE:592	Reduced, survival
AOP:95		Unclassified	-	0.33	KE:593	Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary System Disease	Under Development	0.36	KE:277	Thyroid hormone synthesis, Decreased
					KE:821	Decreased, Sodium reabsorption
					KE:825	Decreased, Renal ability to dilute urine
					KE:814	Occurrence, Kidney toxicity
AOP:205	AOP from chemical insult to cell death	Unclassified	-	0.5	KE:1259	narcosis
					KE:177	Mitochondrial dysfunction
					KE:1262	Apoptosis
AOP:261	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility	Cardiovascular System Disease	Under Development	0.38	KE:1529	Blockade, L-Type Calcium Channels
					KE:1532	Decrease, Cardiac contractility
					KE:1535	Heart failure
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	1.0	KE:1821	Decrease, Cell proliferation
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1446	Decrease, Coupling of oxidative phosphorylation
					KE:1521	Decrease, Growth
AOP:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development	1.0	KE:1771	Decrease, Adenosine triphosphate pool
					KE:55	Increase, Cell injury/death
					KE:1446	Decrease, Coupling of oxidative phosphorylation
					KE:1521	Decrease, Growth
AOP:265	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium	Unclassified	Under Development	0.75	KE:1521	Decrease, Growth
					KE:55	Increase, Cell injury/death
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:266	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity	Unclassified	Under Development	0.83	KE:1521	Decrease, Growth
					KE:1562	Decreased Na/K ATPase activity
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1446	Decrease, Coupling of oxidative phosphorylation
					KE:55	Increase, Cell injury/death
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development	0.6	KE:1821	Decrease, Cell proliferation
					KE:1521	Decrease, Growth
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:268	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling	Unclassified	Under Development	0.75	KE:1521	Decrease, Growth
					KE:55	Increase, Cell injury/death
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:324	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death	Unclassified	-	0.75	KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
					KE:55	Increase, Cell injury/death
AOP:325	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death	Unclassified	-	0.75	KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
					KE:55	Increase, Cell injury/death
AOP:326	Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death	Unclassified	-	0.75	KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
					KE:55	Increase, Cell injury/death
AOP:331	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation	Unclassified	-	0.5	KE:1821	Decrease, Cell proliferation
					KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-	0.6	KE:1821	Decrease, Cell proliferation
					KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-	1.0	KE:1521	Decrease, Growth
					KE:1115	Increase, Reactive oxygen species
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1446	Decrease, Coupling of oxidative phosphorylation
					KE:1821	Decrease, Cell proliferation
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary System Disease	-	0.25	KE:177	Mitochondrial dysfunction
					KE:814	Occurrence, Kidney toxicity
					KE:759	Increased, Kidney Failure
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.33	KE:149	Increase, Inflammation
					KE:1115	Increase, Reactive oxygen species
					KE:759	Increased, Kidney Failure
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive Disorder	-	0.43	KE:1115	Increase, Reactive oxygen species
					KE:1869	Diminished protective oxidative stress response
					KE:402	Cognitive function, decreased
AOP:499	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release	Developmental Disorder Of Mental Health	-	1.0	KE:2146	Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2
					KE:1339	Increase, intracellular calcium
					KE:341	Impairment, Learning and memory
					KE:2151	Disruption, neurotransmitter release
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental Disorder Of Mental Health	-	1.0	KE:1262	Apoptosis
					KE:2146	Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2
					KE:177	Mitochondrial dysfunction
					KE:1115	Increase, Reactive oxygen species
					KE:352	N/A, Neurodegeneration
					KE:1339	Increase, intracellular calcium
					KE:341	Impairment, Learning and memory
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.6	KE:149	Increase, Inflammation
					KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular System Disease	-	0.19	KE:1115	Increase, Reactive oxygen species
					KE:2161	Increase, Vascular disrupting effects
					KE:177	Mitochondrial dysfunction
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	0.6	KE:1115	Increase, Reactive oxygen species
					KE:1060	Alteration, lipid metabolism
					KE:885	Increase, Cancer
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular System Disease	-	0.43	KE:1562	Decreased Na/K ATPase activity
					KE:2261	Decreased, blood plasma volume
					KE:1535	Heart failure
AOP:552	Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)	Cardiovascular System Disease	-	1.0	KE:698	Altered, Action Potential
					KE:2281	Increased uncoordinated cardiac contraction
					KE:1529	Blockade, L-Type Calcium Channels
					KE:1963	Torsades de Pointes
					KE:1535	Heart failure
					KE:1962	Prolongation of QT interval
AOP:555	Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure	Cardiovascular System Disease	-	1.0	KE:2283	Increased the early premature depolarizations during repolarization
					KE:1961	Prolongation of Action Potential Duration
					KE:593	Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel
					KE:1535	Heart failure
					KE:1962	Prolongation of QT interval
AOP:556	Decreased Na/K ATPase activity leading to heart failure	Cardiovascular System Disease	-	1.0	KE:389	Increased, Intracellular Calcium overload
					KE:1532	Decrease, Cardiac contractility
					KE:1321	Increased, intracellular sodium (Na+)
					KE:1562	Decreased Na/K ATPase activity
					KE:2287	Impaired Sodium-Calcium Exchange
					KE:1535	Heart failure
AOP:558	Phosphodiesterase inhibition leading to heart failure	Cardiovascular System Disease	-	1.0	KE:389	Increased, Intracellular Calcium overload
					KE:1532	Decrease, Cardiac contractility
					KE:2289	Hyperphosphorylation of ryanodine receptor (RyR2)
					KE:2288	Phosphodiesterase inhibition
					KE:1535	Heart failure
					KE:693	Increased, cyclic adenosine monophosphate
AOP:560	Inhibition of Funny current (If) leading to Arrhythmias	Symptom	-	1.0	KE:1106	Occurrence, cardiac arrhythmia
					KE:2290	Inhibition of Funny current (If)
					KE:2291	Slowed Heart Rate
					KE:2292	Altered Cardiac Electrical Conduction

Glossary of Terms

AOP: Adverse Outcome Pathway
MIE: Molecular Initiating Event
KE: Key Event
AO: Adverse Outcome
Coverage score: The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints
Level of relevance: Qualitative rank based on the kind of associated KEs within the corresponding AOP
AO classification: The disease category corresponding to the AO in the AOP obtained from Disease Ontology

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
CTD - Phenotype	-
CTD - Disease	MESH:D020078 - Neurogenic Inflammation
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D003248 - Constipation
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007268 - chemical synaptic transmission
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007268 - chemical synaptic transmission
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006281 - DNA repair GO:0006974 - cellular response to DNA damage stimulus
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009784 - Occupational Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	inhibit spermatogenesis at the pre-meiotic stage via lack of testosterone production from Leydig cells
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testosterone levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0050729 - positive regulation of inflammatory response GO:0006954 - inflammatory response GO:0002523 - leukocyte migration involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	GO:0072593 - reactive oxygen species metabolic process GO:0050665 - hydrogen peroxide biosynthetic process GO:1903428 - positive regulation of reactive oxygen species biosynthetic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006954 - inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	MESH:D006965 - Hyperplasia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006915 - apoptotic process
CTD - Disease	MESH:D064806 - Dysbiosis
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D056486 - Chemical and Drug Induced Liver Injury MESH:D008107 - Liver Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006641 - triglyceride metabolic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006915 - apoptotic process GO:0043065 - positive regulation of apoptotic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Reduced sperm counts
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging Protypical stressor of AOP:499 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	GO:0007612 - learning GO:0007611 - learning or memory GO:0007613 - memory
CTD - Disease	MESH:D007859 - Learning Disabilities
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D007859 - Learning Disabilities D008569 - Memory Deficits
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006281 - DNA repair GO:0006974 - cellular response to DNA damage stimulus
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D001259 - Ataxia
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007268 - chemical synaptic transmission GO:0016079 - synaptic vesicle exocytosis
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:558 - Phosphodiesterase inhibition leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:552 - Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D011041 - Poisoning MESH:D007855 - Lead Poisoning
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0042403 - thyroid hormone metabolic process GO:0006590 - thyroid hormone generation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Increased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D001259 - Ataxia
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0050729 - positive regulation of inflammatory response GO:0006954 - inflammatory response GO:0002523 - leukocyte migration involved in inflammatory response
CTD - Disease	MESH:D005128 - Eye Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Increased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007268 - chemical synaptic transmission
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0050729 - positive regulation of inflammatory response GO:0006954 - inflammatory response GO:0002523 - leukocyte migration involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:1900017 - positive regulation of cytokine production involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D013959 - Thyroid Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	GO:0006915 - apoptotic process GO:0043065 - positive regulation of apoptotic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006281 - DNA repair GO:0006974 - cellular response to DNA damage stimulus
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D047928 - Premature Birth
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects sexual behavior
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:556 - Decreased Na/K ATPase activity leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D015352 - Dry Eye Syndromes
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001172 - Arthritis, Rheumatoid MESH:D010182 - Pancreatic Diseases MESH:D001847 - Bone Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects survival of live fetus
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D000013 - Congenital Abnormalities
DEDuCT - endocrine-mediated endpoint	Affects developmental process
NeurotoxKb - neurotoxic endpoints	D009421 - Nervous System Malformations D065886 - Neurodevelopmental Disorders
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001848 - Bone Diseases, Developmental
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0030154 - cell differentiation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008584 - male gonad development
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	-
CTD - Disease	MESH:D009410 - Nerve Degeneration
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D009410 - Nerve Degeneration D016472 - Motor Neuron Disease
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0034599 - cellular response to oxidative stress GO:0006979 - response to oxidative stress
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006754 - ATP biosynthetic process GO:0046034 - ATP metabolic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008285 - negative regulation of cell population proliferation GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D042822 - Genomic Instability
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007605 - sensory perception of sound
CTD - Disease	MESH:D034381 - Hearing Loss
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D007676 - Kidney Failure, Chronic
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D007154 - Immune System Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D002292 - Carcinoma, Renal Cell MESH:D008579 - Meningioma
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D048629 - Micronuclei, Chromosome-Defective MESH:D002869 - Chromosome Aberrations
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus Type of genotoxicity: chromosome aberration - positive
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:556 - Decreased Na/K ATPase activity leading to heart failure Protypical stressor of AOP:558 - Phosphodiesterase inhibition leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D002658 - Developmental Disabilities MESH:D011297 - Prenatal Exposure Delayed Effects
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D002869 - Chromosome Aberrations
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus Type of genotoxicity: chromosome aberration - positive
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:556 - Decreased Na/K ATPase activity leading to heart failure Protypical stressor of AOP:558 - Phosphodiesterase inhibition leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006915 - apoptotic process GO:0051402 - neuron apoptotic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:555 - Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:555 - Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:499 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D015431 - Weight Loss MESH:D000855 - Anorexia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D007248 - Infertility, Male MESH:D009845 - Oligospermia MESH:D000072660 - Teratozoospermia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D066126 - Cardiotoxicity MESH:D002318 - Cardiovascular Diseases MESH:D001018 - Aortic Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects survival of live fetus
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D005234 - Fatty Liver
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0050890 - cognition GO:0007612 - learning GO:0007611 - learning or memory GO:0007613 - memory
CTD - Disease	MESH:D003072 - Cognition Disorders MESH:D001008 - Anxiety Disorders MESH:D060825 - Cognitive Dysfunction
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D060825 - Cognitive Dysfunction
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0000902 - cell morphogenesis
CTD - Disease	MESH:D001848 - Bone Diseases, Developmental MESH:D002658 - Developmental Disabilities MESH:D008064 - Lipidoses
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects survival of live fetus
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D002292 - Carcinoma, Renal Cell
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	renal tumours
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D007248 - Infertility, Male MESH:D013733 - Testicular Diseases MESH:D007172 - Erectile Dysfunction MESH:D009845 - Oligospermia MESH:D000072660 - Teratozoospermia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008203 - cholesterol metabolic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D011164 - Porphyrias
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D008175 - Lung Neoplasms MESH:D009369 - Neoplasms MESH:D002292 - Carcinoma, Renal Cell MESH:D008579 - Meningioma MESH:D001254 - Astrocytoma MESH:D018242 - Neuroectodermal Tumors, Primitive
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006973 - Hypertension MESH:D046110 - Hypertension, Pregnancy-Induced
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D011225 - Pre-Eclampsia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0050729 - positive regulation of inflammatory response GO:0006954 - inflammatory response GO:0002523 - leukocyte migration involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testis weights
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D056486 - Chemical and Drug Induced Liver Injury
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0034599 - cellular response to oxidative stress GO:0006979 - response to oxidative stress
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006529 - Hepatomegaly
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D050197 - Atherosclerosis MESH:D003324 - Coronary Artery Disease
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D005317 - Fetal Growth Retardation
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D000419 - Albuminuria
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009410 - Nerve Degeneration MESH:D019636 - Neurodegenerative Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D009410 - Nerve Degeneration D016472 - Motor Neuron Disease
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001848 - Bone Diseases, Developmental MESH:D002658 - Developmental Disabilities MESH:D006130 - Growth Disorders
DEDuCT - endocrine-mediated endpoint	Affects developmental process
NeurotoxKb - neurotoxic endpoints	D009421 - Nervous System Malformations D065886 - Neurodevelopmental Disorders
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D001259 - Ataxia
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D008175 - Lung Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D019465 - Craniofacial Abnormalities
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D010523 - Peripheral Nervous System Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007268 - chemical synaptic transmission
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006754 - ATP biosynthetic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D008175 - Lung Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009845 - Oligospermia
DEDuCT - endocrine-mediated endpoint	Reduced sperm counts
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects survival of live fetus
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D007674 - Kidney Diseases MESH:D051436 - Renal Insufficiency, Chronic
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006954 - inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D018149 - Glucose Intolerance MESH:D003920 - Diabetes Mellitus
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006943 - Hyperglycemia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:552 - Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP) Protypical stressor of AOP:555 - Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:552 - Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D003643 - Death
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D003924 - Diabetes Mellitus, Type 2 MESH:D007333 - Insulin Resistance
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D060825 - Cognitive Dysfunction D007859 - Learning Disabilities
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009765 - Obesity
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D005234 - Fatty Liver
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D024821 - Metabolic Syndrome MESH:D006943 - Hyperglycemia MESH:D019189 - Iron Metabolism Disorders MESH:D006962 - Hyperparathyroidism, Secondary
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009410 - Nerve Degeneration MESH:D065886 - Neurodevelopmental Disorders MESH:D001930 - Brain Injuries MESH:D000090862 - Neuroinflammatory Diseases MESH:D010300 - Parkinson Disease
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D009410 - Nerve Degeneration
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009422 - Nervous System Diseases MESH:D065886 - Neurodevelopmental Disorders MESH:D001321 - Autistic Disorder MESH:D001930 - Brain Injuries MESH:D008569 - Memory Disorders MESH:D000090862 - Neuroinflammatory Diseases MESH:D008607 - Intellectual Disability MESH:D000690 - Amyotrophic Lateral Sclerosis MESH:D020078 - Neurogenic Inflammation MESH:D019957 - Motor Skills Disorders MESH:D000067877 - Autism Spectrum Disorder MESH:D011596 - Psychomotor Disorders MESH:D000068079 - Motor Disorders MESH:D010300 - Parkinson Disease MESH:D003072 - Cognition Disorders MESH:D006948 - Hyperkinesis MESH:D001289 - Attention Deficit Disorder with Hyperactivity MESH:D009069 - Movement Disorders MESH:D003704 - Dementia MESH:D019954 - Neurobehavioral Manifestations MESH:D016472 - Motor Neuron Disease MESH:D020329 - Essential Tremor MESH:D014202 - Tremor MESH:D002493 - Central Nervous System Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D065886 - Neurodevelopmental Disorders
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001018 - Aortic Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D001930 - Brain Injuries D001929 - Brain Edema
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testis weights
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	D011596 - Psychomotor Disorders
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0051881 - regulation of mitochondrial membrane potential
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:552 - Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP) Protypical stressor of AOP:555 - Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure Protypical stressor of AOP:556 - Decreased Na/K ATPase activity leading to heart failure Protypical stressor of AOP:558 - Phosphodiesterase inhibition leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:560 - Inhibition of Funny current (If) leading to Arrhythmias
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:560 - Inhibition of Funny current (If) leading to Arrhythmias
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:560 - Inhibition of Funny current (If) leading to Arrhythmias
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009410 - Nerve Degeneration
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0005515 - protein binding
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0050729 - positive regulation of inflammatory response GO:0006954 - inflammatory response GO:0002523 - leukocyte migration involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008203 - cholesterol metabolic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007268 - chemical synaptic transmission
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D056486 - Chemical and Drug Induced Liver Injury
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D011507 - Proteinuria
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006750 - glutathione biosynthetic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0004364 - glutathione transferase activity
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0010468 - regulation of gene expression
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006979 - response to oxidative stress
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D004487 - Edema
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0001774 - microglial cell activation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D050171 - Dyslipidemias
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:12 - Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D003876 - Dermatitis, Atopic MESH:D004485 - Eczema
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:1900017 - positive regulation of cytokine production involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:555 - Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0003014 - renal system process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D051437 - Renal Insufficiency
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007009 - plasma membrane organization
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:552 - Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:499 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:499 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release Protypical stressor of AOP:500 - Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006629 - lipid metabolic process
CTD - Disease	MESH:D006949 - Hyperlipidemias
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008217 - regulation of blood pressure
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:552 - Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:556 - Decreased Na/K ATPase activity leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:556 - Decreased Na/K ATPase activity leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:558 - Phosphodiesterase inhibition leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:558 - Phosphodiesterase inhibition leading to heart failure
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:560 - Inhibition of Funny current (If) leading to Arrhythmias
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

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DISCLAIMER

TICToK is a knowledgebase of chemicals found in tattoo inks, compiled from publicly available regulatory and scientific resources. The chemical classifications presented in this knowledgebase are derived from multiple publicly available resources and are provided solely for informational purposes, and they are neither authoritative nor binding. The chemical-AOP mappings compiled in this knowledgebase serve as plausible hypotheses for research, and further experimental validation is required to definitively establish these potential toxicity mechanisms. The authors bear no responsibility for any errors, omissions, or inconsistencies originating from these external sources. Users are advised to exercise independent judgment when interpreting chemical classifications and any other data provided in this resource. Importantly, our sole goal to build this resource on tattoo ink chemicals is to enable future basic research on this topic, and it does not necessarily reflect the views or objectives of our employers or funders.

Lead

Associated AOPs with Level of Relevance 1 AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

Associated AOPs with Level of Relevance 2AOPs with at least 1 AO associated with chemical, and no associated MIE

Associated AOPs with Level of Relevance 3AOPs with at least 1 MIE associated with chemical, and no associated AO

Associated AOPs with Level of Relevance 5AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO

Glossary of Terms

Associated AOPs with Level of Relevance 1
AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

Associated AOPs with Level of Relevance 2
AOPs with at least 1 AO associated with chemical, and no associated MIE

Associated AOPs with Level of Relevance 3
AOPs with at least 1 MIE associated with chemical, and no associated AO

Associated AOPs with Level of Relevance 5
AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO