TICToK | Tattoo Ink Chemicals and associated Toxicities Knowledgebase

Triclosan

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: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: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	0.12	KE:55	Increase, Cell injury/death
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	0.1	KE:55	Increase, Cell injury/death
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: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	0.2	KE:55	Increase, Cell injury/death
AOP:17		Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.2	KE:1392	Oxidative Stress
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:274	Reduction, Testosterone synthesis by ovarian theca cells
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	0.25	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	0.25	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	0.25	KE:1115	Increase, Reactive oxygen species
AOP:27		Gastrointestinal System Disease	Under Development	0.25	KE:288	Activation of specific nuclear receptors, Transcriptional change
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal System Disease	WPHA/WNT Endorsed	0.14	KE:55	Increase, Cell injury/death
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	WPHA/WNT Endorsed	0.12	KE:281	Thyroxine (T4) in serum, Decreased
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	0.11	KE:55	Increase, Cell injury/death
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.1	KE:281	Thyroxine (T4) in serum, Decreased
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.12	KE:458	Increased, De Novo FA synthesis
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis		-	0.12	KE:454	Increased, Triglyceride formation
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:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	0.12	KE:664	Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive System Disease	-	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
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:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary System Disease	-	0.17	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
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:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:110		Cancer; Endocrine System Disease	-	0.29	KE:281	Thyroxine (T4) in serum, Decreased
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:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive System Disease; Cancer	-	0.5	KE:747	Decreased, Prolactin
					KE:111	Agonism, Estrogen receptor
					KE:749	Decreased, Progesterone from corpus luteum
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	0.17	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	0.2	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary System Disease	-	0.25	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:119		Cancer; Endocrine System Disease	-	0.29	KE:281	Thyroxine (T4) in serum, Decreased
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:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary System Disease	-	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:122		Unclassified	-	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	0.18	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123		Unclassified	-	0.18	KE:219	Reduction, Plasma 17beta-estradiol concentrations
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:128	Kidney dysfunction by decreased thyroid hormone	Urinary System Disease	Under Development	0.18	KE:821	Decreased, Sodium reabsorption
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary System Disease	Under Development	0.18	KE:281	Thyroxine (T4) in serum, Decreased
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.11	KE:281	Thyroxine (T4) in serum, Decreased
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	0.11	KE:55	Increase, Cell injury/death
AOP:155	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:156	Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:157	Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:158	Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:159		Unclassified	WPHA/WNT Endorsed	0.25	KE:1003	Decreased, Triiodothyronine (T3)
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:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:167		Reproductive System Disease; Cancer	-	0.29	KE:1065	Activation, estrogen receptor alpha
AOP:173	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis	Musculoskeletal System Disease; Respiratory System Disease	WPHA/WNT Endorsed	0.12	KE:1496	Increased, secretion of proinflammatory mediators
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:189	Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.5	KE:1116	Decreased, Triiodothyronine (T3) in tissues
AOP:189		Unclassified	-	0.5	KE:1003	Decreased, Triiodothyronine (T3)
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.33	KE:1116	Decreased, Triiodothyronine (T3) in tissues
AOP:190		Unclassified	-	0.33	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:191	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.5	KE:1154	Increased, Triiodothyronine (T3) in tissues
AOP:191		Unclassified	-	0.5	KE:1829	Altered, Thyroid hormone-dependent gene expression
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	0.17	KE:281	Thyroxine (T4) in serum, Decreased
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive System Disease	-	0.38	KE:1281	Increased, DNA Damage-Repair
					KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
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:237	Substance interaction with lung resident cell membrane components leading to atherosclerosis	Cardiovascular System Disease	Under Development	0.2	KE:1496	Increased, secretion of proinflammatory mediators
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous System Disease	-	0.14	KE:1392	Oxidative Stress
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.43	KE:870	Increase, Cell Proliferation
					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:1558	Collagen production, reduced
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural Tube Defect	-	0.2	KE:1560	Altered differentiation
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-	0.12	KE:55	Increase, Cell injury/death
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous System Disease	-	0.1	KE:55	Increase, Cell injury/death
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:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-	0.14	KE:1115	Increase, Reactive oxygen species
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.43	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1669	Increased, DNA damage and mutation
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:309	Luteinizing hormone receptor antagonism leading to reproductive dysfunction	Unclassified	-	0.29	KE:1693	Reduction, Plasma progesterone concentration
AOP:309		Unclassified	-	0.29	KE:1692	Reduction, Progesterone synthesis
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	0.11	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:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary System Disease	-	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:346	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation	Unclassified	WPHA/WNT Endorsed	0.2	KE:1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:348	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory	Unclassified	Under Development	0.2	KE:1758	Impaired, Spermatogenesis
AOP:362	Immune mediated hepatitis	Gastrointestinal System Disease; Immune System Disease	-	0.12	KE:1817	Apoptotic cell death
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:363		Unclassified	Under Review	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:364		Unclassified	Under Development	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:365		Unclassified	Under Development	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:366	Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis	Unclassified	-	0.14	KE:281	Thyroxine (T4) in serum, Decreased
AOP:367	Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis	Unclassified	-	0.14	KE:281	Thyroxine (T4) in serum, Decreased
AOP:368	Cytochrome oxidase inhibition leading to increased nasal lesions	Unclassified	-	0.33	KE:1825	Increase, Cell death
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:1115	Increase, Reactive oxygen species
AOP:387		Reproductive System Disease	-	0.25	KE:1770	Decrease, Mitochondrial membrane potential
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive System Disease	-	0.2	KE:1864	Increase, Programmed cell death
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	-	0.12	KE:1821	Decrease, Cell proliferation
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.5	KE:1669	Increased, DNA damage and mutation
					KE:870	Increase, Cell Proliferation
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	0.1	KE:1825	Increase, Cell death
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic System Disease; Cancer	-	0.18	KE:870	Increase, Cell Proliferation
AOP:432		Hematopoietic System Disease; Cancer	-	0.18	KE:155	Inadequate DNA repair
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary System Disease	Under Development	0.2	KE:1392	Oxidative Stress
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:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-	0.22	KE:1365	Increase, Apoptosis
AOP:444		Unclassified	-	0.22	KE:1392	Oxidative Stress
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous System Disease	-	0.14	KE:1392	Oxidative Stress
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.44	KE:1669	Increased, DNA damage and mutation
					KE:870	Increase, Cell Proliferation
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.18	KE:1262	Apoptosis
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.18	KE:1392	Oxidative Stress
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	0.22	KE:1821	Decrease, Cell proliferation
AOP:460		Unclassified	Under Development	0.22	KE:1262	Apoptosis
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous System Disease	-	0.11	KE:1825	Increase, Cell death
AOP:464		Nervous System Disease	-	0.11	KE:1392	Oxidative Stress
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.25	KE:748	Increased, Estrogen receptor (ER) activity
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.25	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	0.25	KE:2244	Altered Stress Response Signaling
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular System Disease	Under Review	0.25	KE:1392	Oxidative Stress
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.4	KE:870	Increase, Cell Proliferation
					KE:1636	Increase, Chromosomal aberrations
					KE:155	Inadequate DNA repair
					KE:1392	Oxidative Stress
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular System Disease; Thoracic Disease	Under Development	0.29	KE:55	Increase, Cell injury/death
AOP:479		Cardiovascular System Disease; Thoracic Disease	Under Development	0.29	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:1825	Increase, Cell death
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:1392	Oxidative Stress
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental Disorder Of Mental Health	Under Review	0.25	KE:2244	Altered Stress Response Signaling
AOP:483		Developmental Disorder Of Mental Health	Under Review	0.25	KE:1392	Oxidative Stress
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental Disorder Of Mental Health	-	0.09	KE:55	Increase, Cell injury/death
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	0.33	KE:1821	Decrease, Cell proliferation
AOP:491		Unclassified	Under Development	0.33	KE:1262	Apoptosis
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive System Disease	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired Metabolic Disease	-	0.1	KE:2119	Insulin resistance, increased
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:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental Disorder Of Mental Health	-	0.29	KE:1115	Increase, Reactive oxygen species
AOP:500		Developmental Disorder Of Mental Health	-	0.29	KE:1262	Apoptosis
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous System Disease	-	0.25	KE:1392	Oxidative Stress
AOP:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular System Disease	-	0.29	KE:1365	Increase, Apoptosis
AOP:509		Cardiovascular System Disease	-	0.29	KE:1392	Oxidative Stress
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular System Disease	-	0.2	KE:2165	Activation of PPAR
AOP:510		Cardiovascular System Disease	-	0.2	KE:1392	Oxidative Stress
AOP:518	Liver X Receptor (LXR) activation leads to liver steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.2	KE:89	Synthesis, De Novo Fatty Acid (FA)
AOP:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal System Disease	-	0.2	KE:55	Increase, Cell injury/death
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental Disorder Of Mental Health	-	0.33	KE:1262	Apoptosis
					KE:2233	Decreased, ERαβ heterodimers
					KE:1392	Oxidative Stress
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular System Disease	-	0.14	KE:2261	Decreased, blood plasma volume
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:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental Disorder Of Mental Health	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:573	Inhibition, cytochrome oxidase leads to Increased, pulmonary edema	Respiratory System Disease	-	0.33	KE:1825	Increase, Cell death
AOP:574	Inhibition, cytochrome oxidase leads to Loss of olfactory function	Unclassified	-	0.33	KE:1825	Increase, Cell death

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:34	LXR activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.15	KE:89	Synthesis, De Novo Fatty Acid (FA)
AOP:34	LXR activation leading to hepatic steatosis		-	0.15	KE:345	N/A, Liver Steatosis
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory System Disease	Under Development	0.6	KE:1496	Increased, secretion of proinflammatory mediators
					KE:272	Activation/Proliferation, T-cells
					KE:313	Increase, Allergic Respiratory Hypersensitivity Response
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary System Disease	WPHA/WNT Endorsed	0.6	KE:827	sensitisation, skin
					KE:826	Activation, Keratinocytes
					KE:272	Activation/Proliferation, T-cells
AOP:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	0.2	KE:1001	Increased, Developmental Defects
AOP:91	Sodium channel inhibition leading to reduced survival	Unclassified	-	0.17	KE:592	Reduced, survival
AOP:95	Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survival	Unclassified	-	0.17	KE:592	Reduced, survival
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	0.14	KE:636	Decreased, survival
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:719	Increase, hepatocellular adenomas and carcinomas
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	-	0.33	KE:768	Increase, Cytotoxicity
AOP:108		Cancer; Gastrointestinal System Disease	-	0.33	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	Under Development	0.5	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:117		Cancer; Gastrointestinal System Disease	Under Development	0.5	KE:716	Increase, cell proliferation (hepatocytes)
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.5	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:118		Cancer; Gastrointestinal System Disease	-	0.5	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
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: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:205	AOP from chemical insult to cell death	Unclassified	-	0.17	KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.5	KE:1506	Testicular atrophy
					KE:1262	Apoptosis
					KE:1505	Cell cycle, disrupted
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal System Disease	WPHA/WNT Endorsed	0.6	KE:1394	Induction, persistent proliferation/sustained proliferation
					KE:1395	Liver Cancer
					KE:1392	Oxidative Stress
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	-	0.09	KE:1521	Decrease, Growth
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: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	-	0.75	KE:1825	Increase, Cell death
					KE:1771	Decrease, Adenosine triphosphate pool
					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	-	0.75	KE:1825	Increase, Cell death
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1521	Decrease, Growth
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.22	KE:1193	N/A, Breast Cancer
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:1193	N/A, Breast Cancer
AOP:294		Genetic Disease; Thoracic Disease; Cancer	Under Development	0.22	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
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:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.6	KE:1757	Reduce, Sperm count
					KE:155	Inadequate DNA repair
					KE:1365	Increase, Apoptosis
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: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: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:440	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia	Benign Neoplasm; Endocrine System Disease; Reproductive System Disease; Reproductive System Disease; Cancer; Endocrine System Disease	Under Development	0.22	KE:1973	Increased, estrogens
AOP:440			Under Development	0.22	KE:2092	Promotion, Ovarian Cancer
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited Metabolic Disorder	-	0.5	KE:281	Thyroxine (T4) in serum, Decreased
					KE:2119	Insulin resistance, increased
					KE:1392	Oxidative Stress
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-	0.38	KE:1868	Hyperinflammation
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1825	Increase, Cell death
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	0.2	KE:885	Increase, Cancer
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:2145	Metabolic syndrome
					KE:2119	Insulin resistance, increased
					KE:1392	Oxidative Stress
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	0.71	KE:1392	Oxidative Stress
					KE:1758	Impaired, Spermatogenesis
					KE:1115	Increase, Reactive oxygen species
					KE:2147	Decreased, Viable Offspring
					KE:2206	Increased, histomorphological alteration of testis
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	0.67	KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
					KE:1446	Decrease, Coupling of oxidative phosphorylation
					KE:1392	Oxidative Stress
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	0.2	KE:885	Increase, Cancer
AOP:561	Aromatase induction leading to estrogen receptor alpha activation via increased estradiol	Unclassified	-	0.6	KE:2251	Estradiol availability, increased
					KE:2294	Plasma estradiol, increased
					KE:1065	Activation, estrogen receptor alpha

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: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:281	Thyroxine (T4) in serum, Decreased
AOP:8		Nervous System Disease	Under Development	0.22	KE:239	Activation, Pregnane-X receptor, NR1l2
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:227	Activation, PPARα
					KE:1690	Decrease, circulating testosterone levels
AOP:36	Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.12	KE:233	Decreased, PPAR-gamma activation
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:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.17	KE:245	Activation, PXR/SXR
AOP:60			-	0.17	KE:454	Increased, Triglyceride formation
AOP:131	Aryl hydrocarbon receptor activation leading to uroporphyria	Inherited Metabolic Disorder	WPHA/WNT Endorsed	0.17	KE:18	Activation, AhR
AOP:151	AhR activation leading to preeclampsia	Cardiovascular System Disease	Under Development	0.14	KE:18	Activation, AhR
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal System Disease	-	0.12	KE:1286	Down Regulation, GSS and GSTs gene
AOP:233	Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening	Developmental Disorder Of Mental Health	-	0.2	KE:1425	Mu Opioid Receptor Agonism
AOP:234	Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition	Developmental Disorder Of Mental Health	-	0.2	KE:1425	Mu Opioid Receptor Agonism
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:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	Under Development	0.2	KE:1656	Antagonism, Thyroid Receptor
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.5	KE:26	Antagonism, Androgen receptor
AOP:306		Unclassified	Under Development	0.5	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:18	Activation, AhR
					KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:327	Excessive reactive oxygen species production leading to mortality (1)	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	0.6	KE:1115	Increase, Reactive oxygen species
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1770	Decrease, Mitochondrial membrane potential
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	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:330		Unclassified	-	0.4	KE:1365	Increase, Apoptosis
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development	0.5	KE:26	Antagonism, Androgen receptor
AOP:344		Unclassified	Under Development	0.5	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	0.33	KE:26	Antagonism, Androgen receptor
AOP:345			Under Development	0.33	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine System Disease; Reproductive System Disease; Cancer	-	0.4	KE:26	Antagonism, Androgen receptor
AOP:372	Androgen receptor antagonism leading to testicular cancer		-	0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory System Disease	-	0.25	KE:1392	Oxidative Stress
AOP:414	Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathway	Musculoskeletal System Disease; Respiratory System Disease	-	0.2	KE:18	Activation, AhR
AOP:415	Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathway	Musculoskeletal System Disease; Respiratory System Disease	-	0.2	KE:18	Activation, AhR
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-	0.5	KE:18	Activation, AhR
					KE:1115	Increase, Reactive oxygen species
					KE:1669	Increased, DNA damage and mutation
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-	0.4	KE:18	Activation, AhR
AOP:417		Cancer	-	0.4	KE:1669	Increased, DNA damage and mutation
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory System Disease	-	0.6	KE:18	Activation, AhR
					KE:1115	Increase, Reactive oxygen species
					KE:1825	Increase, Cell death
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory System Disease	-	0.5	KE:18	Activation, AhR
AOP:419		Respiratory System Disease	-	0.5	KE:1262	Apoptosis
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-	0.75	KE:18	Activation, AhR
					KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
					KE:870	Increase, Cell Proliferation
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory System Disease	-	0.17	KE:1392	Oxidative Stress
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:1392	Oxidative Stress
AOP:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive System Disease	-	0.12	KE:1065	Activation, estrogen receptor alpha
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.3	KE:18	Activation, AhR
					KE:1262	Apoptosis
					KE:1392	Oxidative Stress
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
					KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary System Disease	-	0.33	KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
					KE:1365	Increase, Apoptosis
					KE:1770	Decrease, Mitochondrial membrane potential
					KE:1392	Oxidative Stress
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:448		Cardiovascular System Disease	-	0.12	KE:1392	Oxidative Stress
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	-	0.15	KE:1115	Increase, Reactive oxygen species
AOP:453		Gastrointestinal System Disease	-	0.15	KE:1392	Oxidative Stress
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.25	KE:18	Activation, AhR
AOP:458		Cognitive Disorder	-	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.33	KE:18	Activation, AhR
					KE:281	Thyroxine (T4) in serum, Decreased
					KE:1392	Oxidative Stress
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal System Disease	-	0.15	KE:1115	Increase, Reactive oxygen species
AOP:469		Gastrointestinal System Disease	-	0.15	KE:1392	Oxidative Stress
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.33	KE:1115	Increase, Reactive oxygen species
					KE:1392	Oxidative Stress
					KE:1825	Increase, Cell death
AOP:477	Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring	Physical Disorder	-	0.33	KE:26	Antagonism, Androgen receptor
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive Disorder	-	0.14	KE:1656	Antagonism, Thyroid Receptor
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:1392	Oxidative Stress
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.33	KE:18	Activation, AhR
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.33	KE:55	Increase, Cell injury/death
AOP:503	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation	Reproductive System Disease; Cancer	Under Review	0.17	KE:1065	Activation, estrogen receptor alpha
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:511		Cardiovascular System Disease	-	0.12	KE:1392	Oxidative Stress
AOP:517	Pregnane X Receptor (PXR) activation leads to liver steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.2	KE:2201	Agonism, Retinoic acid receptor
AOP:523	Retinoic acid receptor agonism during neurodevelopment leading to microcephaly	Congenital Nervous System Abnormality; Nervous System Disease	-	0.2	KE:2201	Agonism, Retinoic acid receptor
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.15	KE:1656	Antagonism, Thyroid Receptor
AOP:525		Developmental Disorder Of Mental Health	-	0.15	KE:2216	Binding of antagonist to thyroid hormone receptor
AOP:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-	0.2	KE:2201	Agonism, Retinoic acid receptor
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-	0.17	KE:111	Agonism, Estrogen receptor
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-	0.4	KE:111	Agonism, Estrogen receptor
AOP:537		Unclassified	-	0.4	KE:364	Impaired development of, Reproductive organs
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:1392	Oxidative Stress
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular System Disease	-	0.15	KE:1115	Increase, Reactive oxygen species
AOP:541		Cardiovascular System Disease	-	0.15	KE:1392	Oxidative Stress
AOP:545	Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesis	Unclassified	-	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:548	Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expression	Unclassified	-	0.2	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive System Disease; Endocrine System Disease	-	0.33	KE:18	Activation, AhR
AOP:563		Reproductive System Disease; Endocrine System Disease	-	0.33	KE:1262	Apoptosis

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:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive System Disease	-	0.6	KE:26	Antagonism, Androgen receptor
					KE:286	Altered, Transcription of genes by the androgen receptor
					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	0.4	KE:18	Activation, AhR
AOP:21		Unclassified	WPHA/WNT Endorsed	0.4	KE:947	Increase, Early Life Stage Mortality
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal System Disease	Under Development	0.6	KE:719	Increase, hepatocellular adenomas and carcinomas
					KE:227	Activation, PPARα
					KE:716	Increase, cell proliferation (hepatocytes)
AOP:69	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell	Reproductive System Disease	-	0.6	KE:645	Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells
					KE:642	Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
					KE:646	Decreased Cholesterol, Decreased sperm quantity and/or quality in the adult testis
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	0.29	KE:18	Activation, AhR
AOP:150		Unclassified	WPHA/WNT Endorsed	0.29	KE:947	Increase, Early Life Stage Mortality
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	0.67	KE:1771	Decrease, Adenosine triphosphate pool
					KE:55	Increase, Cell injury/death
					KE:1446	Decrease, Coupling of oxidative phosphorylation
					KE:1521	Decrease, Growth
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	1.0	KE:1521	Decrease, Growth
					KE:55	Increase, Cell injury/death
					KE:2072	Increase, Mitochondrial swelling
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	0.67	KE:2147	Decreased, Viable Offspring
					KE:227	Activation, PPARα
					KE:807	Decreased, cholesterol
					KE:1758	Impaired, Spermatogenesis
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	-	0.67	KE:1821	Decrease, Cell proliferation
					KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
					KE:1505	Cell cycle, disrupted
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-	0.8	KE:1821	Decrease, Cell proliferation
					KE:1115	Increase, Reactive oxygen species
					KE:1521	Decrease, Growth
					KE:1505	Cell cycle, disrupted
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:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	0.6	KE:1866	Fibrinolysis, decreased
					KE:1868	Hyperinflammation
					KE:1496	Increased, secretion of proinflammatory mediators
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:1817	Apoptotic cell death
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.56	KE:18	Activation, AhR
					KE:1262	Apoptosis
					KE:1971	Increased, tumor growth
					KE:1241	Increased, Motility
					KE:1982	metastatic breast cancer
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic Disease; Cancer	Under Development	0.3	KE:1669	Increased, DNA damage and mutation
					KE:155	Inadequate DNA repair
					KE:1982	metastatic breast cancer
AOP:455	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development	Musculoskeletal System Disease	Under Review	0.33	KE:18	Activation, AhR
AOP:455		Musculoskeletal System Disease	Under Review	0.33	KE:947	Increase, Early Life Stage Mortality
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	0.33	KE:18	Activation, AhR
AOP:456		Unclassified	Under Review	0.33	KE:947	Increase, Early Life Stage Mortality
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.36	KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:1392	Oxidative Stress
					KE:2034	liver dysfunction
AOP:504	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level	Unclassified	-	1.0	KE:2251	Estradiol availability, increased
					KE:2155	Inhibition of Sulfotransferase E1 (SULT1E1)
					KE:1065	Activation, estrogen receptor alpha
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.6	KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
					KE:1392	Oxidative Stress
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:885	Increase, Cancer
					KE:233	Decreased, PPAR-gamma activation

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	-
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	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Shafer_MEA_dev_LDH - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	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	Oxidative stress in liver Oxidative stress in nervous system
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:2000224 - regulation of testosterone 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:1903428 - positive regulation of reactive oxygen species biosynthetic process GO:0072593 - reactive oxygen species metabolic process GO:1903426 - 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	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_PPARg_TRANS - gain ATG_PXR_TRANS - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decrease in T4 levels Decrease in T4 levels in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006631 - fatty acid 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: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:2000224 - regulation of testosterone 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	-
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:0006915 - apoptotic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Alterations in number of leydig cells
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 in offspring Reduced sperm quality
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	-
CTD - Phenotype	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	Decreased LH levels
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	GO:0008284 - positive 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	-
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	Decreased prolactin 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	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_ERa_TRANS - gain ATG_zfER2a_XSP1 - gain ATG_frER2_XSP1 - gain ATG_hERa_XSP1 - gain ATG_trERa_XSP1 - gain ATG_chERa_XSP2 - gain ATG_hERa_XSP2 - gain

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive 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	GO:0008284 - positive 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	-
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:0008284 - positive 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	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:D011041 - Poisoning
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	VALA_TUBIPS_Agonist_CellCount - loss VALA_TUBIPS_Antagonist_CellCount - loss CCTE_Simmons_CellTiterGLO_HEK293T - loss CPHEA_Stoker_NIS_Cytotoxicity - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive 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	-
DEDuCT - endocrine-mediated endpoint	Decrease in T3 levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive 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	GO:0008284 - positive 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	Protypical stressor of AOP:504 - SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_ERa_TRANS - gain

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	-
DEDuCT - endocrine-mediated endpoint	Decrease in T3 levels Decrease in T3 levels in offspring
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	ATG_hTRa_XSP1 - gain ATG_frTRa_XSP2 - gain ATG_hTRb_XSP2 - gain TOX21_TR_LUC_GH3_Antagonist - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_TR_LUC_GH3_Antagonist - loss

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D019457 - Chromosome Breakage
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	-
ToxCast invitrodb v4.2	BSK_hDFCGF_CollagenIII - inhibitory

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D019457 - Chromosome Breakage
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	-
ToxCast invitrodb v4.2	OT_AR_ARSRC1_0960 - gain

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Induce apoptosis of placental cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects implantation in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Shafer_MEA_dev_LDH - loss

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	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_MitoMembPot_24hr - inhibitory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Induce apoptosis of placental cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:263 - Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
CTD - Phenotype	GO:0008283 - cell population proliferation GO:0008285 - negative regulation of 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	Induce apoptosis of placental cells
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	-
ToxCast invitrodb v4.2	ATG_ERa_TRANS - gain ATG_zfER2a_XSP1 - gain ATG_frER2_XSP1 - gain ATG_hERa_XSP1 - gain ATG_trERa_XSP1 - gain ATG_chERa_XSP2 - gain ATG_hERa_XSP2 - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D000014 - Abnormalities, Drug-Induced 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	-
DEDuCT - endocrine-mediated endpoint	Oxidative stress in liver Oxidative stress in nervous system
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	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	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:0006915 - 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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_PPRE_CIS - activatory ATG_PPARg_TRANS - gain ATG_hPPARg_XSP1 - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006631 - fatty acid 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	-
DEDuCT - endocrine-mediated endpoint	Affects expression of estrogen receptor-alpha (ER-alpha) in offspring Affects expression of estrogen receptor-alpha (ER-alpha)
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	-
CTD - Phenotype	-
CTD - Disease	MESH:D001835 - Body Weight
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D065626 - Non-alcoholic Fatty Liver Disease
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation GO:0008283 - cell population proliferation
CTD - Disease	MESH:D006967 - Hypersensitivity
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D065631 - Rhinitis, Allergic
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
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	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Padilla_ZF_144hpf_TERATOSCORE - gain

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	-
DEDuCT - endocrine-mediated endpoint	Hepatocellular carcinoma
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive 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	GO:0008284 - positive 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:D007248 - Infertility, Male
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:D008325 - Mammary Neoplasms, Experimental
DEDuCT - endocrine-mediated endpoint	Cancer phenotype Ovarian carcinoma Hepatocellular carcinoma Induce tumor progression
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	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_CellCycleArrest_1hr - inhibitory APR_HepG2_CellCycleArrest_24hr - inhibitory

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:D006529 - Hepatomegaly
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:263 - Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
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:D012734 - Disorders of Sex Development
DEDuCT - endocrine-mediated endpoint	Affects developmental process
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:263 - Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
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	-
DEDuCT - endocrine-mediated endpoint	Occurrence of mammary gland tumor
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive 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	-
DEDuCT - endocrine-mediated endpoint	Reduced sperm counts in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0032731 - positive regulation of interleukin-1 beta production
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
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	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_ERa_TRANS - gain ATG_zfER2a_XSP1 - gain ATG_frER2_XSP1 - gain ATG_hERa_XSP1 - gain ATG_trERa_XSP1 - gain ATG_chERa_XSP2 - gain ATG_hERa_XSP2 - gain

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

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:263 - Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
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:504 - SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Increased 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	Increased 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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_PXRE_CIS - activatory

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

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006915 - 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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_Ahr_CIS - activatory

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

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

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	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	NVS_GPCR_hOpiate_mu - loss

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	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_TR_LUC_GH3_Antagonist - loss

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_NRF2_ARE_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_DR5_RAR_CIS - activatory ATG_RXRb_TRANS - gain

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D012734 - Disorders of Sex Development
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
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D020964 - Embryo Loss
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:2000224 - regulation of testosterone biosynthetic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testosterone levels in offspring
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	-
DEDuCT - endocrine-mediated endpoint	Reduced sperm quality
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	-
ToxCast invitrodb v4.2	APR_HepG2_MitoMass_24hr - activatory APR_HepG2_MitoMass_72hr - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	BSK_3C_uPAR - inhibitory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Cancer phenotype Ovarian carcinoma Hepatocellular carcinoma Induce tumor progression
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0016477 - cell migration
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	Occurrence of mammary gland tumor
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D008114 - Liver Neoplasms, Experimental
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	Protypical stressor of AOP:504 - SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level
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.

Triclosan

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