TICToK | Tattoo Ink Chemicals and associated Toxicities Knowledgebase

Benz(a)anthracene

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:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	WPHA/WNT Endorsed	0.12	KE:277	Thyroid hormone synthesis, Decreased
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:277	Thyroid hormone synthesis, Decreased
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.14	KE:277	Thyroid hormone synthesis, Decreased
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive System Disease; Cancer	-	0.17	KE:111	Agonism, Estrogen receptor
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.14	KE:277	Thyroid hormone synthesis, Decreased
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	0.1	KE:799	Increased, HIF-1 heterodimer
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.11	KE:277	Thyroid hormone synthesis, Decreased
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign Neoplasm; Respiratory System Disease	Under Review	0.14	KE:768	Increase, Cytotoxicity
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.12	KE:277	Thyroid hormone synthesis, Decreased
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive System Disease	-	0.12	KE:1280	Activation, HIF-1
AOP:232	NFE2/Nrf2 repression to steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.12	KE:1419	Reduced, FXR activity
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	0.25	KE:1821	Decrease, Cell proliferation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development	0.2	KE:1821	Decrease, Cell proliferation
AOP:268	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling	Unclassified	Under Development	0.25	KE:2072	Increase, Mitochondrial swelling
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	0.25	KE:1821	Decrease, Cell proliferation
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:1614	Decrease, androgen receptor activation
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	0.25	KE:1821	Decrease, Cell proliferation
AOP:297	Inhibition of retinaldehyde dehydrogenase leads to population decline	Unclassified	Under Development	0.17	KE:1643	Altered, Visual function
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.14	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:1614	Decrease, androgen receptor activation
AOP:327	Excessive reactive oxygen species production leading to mortality (1)	Unclassified	-	0.2	KE:1769	Increase, Body fluid overload
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	0.2	KE:1770	Decrease, Mitochondrial membrane potential
AOP:331	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation	Unclassified	-	0.33	KE:1821	Decrease, Cell proliferation
AOP:331		Unclassified	-	0.33	KE:1505	Cell cycle, disrupted
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-	0.4	KE:1821	Decrease, Cell proliferation
AOP:332		Unclassified	-	0.4	KE:1505	Cell cycle, disrupted
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-	0.2	KE:1821	Decrease, Cell proliferation
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:363		Unclassified	Under Review	0.25	KE:1643	Altered, Visual function
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:364		Unclassified	Under Development	0.25	KE:1643	Altered, Visual function
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:365		Unclassified	Under Development	0.25	KE:1643	Altered, Visual function
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular System Disease	Under Development	0.14	KE:1845	Coagulation
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive System Disease	-	0.12	KE:1770	Decrease, Mitochondrial membrane potential
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	0.25	KE:1821	Decrease, Cell proliferation
AOP:399		Unclassified	-	0.25	KE:1643	Altered, Visual function
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.12	KE:1669	Increased, DNA damage and mutation
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	0.11	KE:1973	Increased, estrogens
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:1974	Activation of Tumor Protein 53
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.1	KE:18	Activation, AhR
AOP:446		Respiratory System Disease	-	0.1	KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:449	Ceramide synthase inhibition leading to neural tube defects	Neural Tube Defect	-	0.14	KE:1502	Histone deacetylase inhibition
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.11	KE:1669	Increased, DNA damage and mutation
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.09	KE:2013	Airway remodeling
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited Metabolic Disorder	-	0.17	KE:277	Thyroid hormone synthesis, Decreased
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	0.11	KE:1821	Decrease, Cell proliferation
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.12	KE:748	Increased, Estrogen receptor (ER) activity
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	0.17	KE:1821	Decrease, Cell proliferation
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular System Disease	-	0.1	KE:2165	Activation of PPAR
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.2	KE:2204	Altered brain morphology

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:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal System Disease	Under Development	0.4	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:37		Cancer; Gastrointestinal System Disease	Under Development	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	0.2	KE:1001	Increased, Developmental Defects
AOP:107	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Cancer; Gastrointestinal System Disease	Under Review	0.6	KE:719	Increase, hepatocellular adenomas and carcinomas
					KE:1214	Altered gene expression specific to CAR activation, Hepatocytes
					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	-	0.25	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.25	KE:885	Increase, Cancer
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal System Disease	WPHA/WNT Endorsed	0.2	KE:1395	Liver Cancer
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.09	KE:2034	liver dysfunction
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	0.2	KE:885	Increase, Cancer
AOP:504	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level	Unclassified	-	0.33	KE:1065	Activation, estrogen receptor alpha
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.2	KE:885	Increase, Cancer
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	0.2	KE:885	Increase, Cancer
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	0.17	KE:885	Increase, Cancer
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	-	0.2	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:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive System Disease	-	0.2	KE:26	Antagonism, Androgen receptor
AOP:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	0.2	KE:18	Activation, AhR
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal System Disease	Under Review	0.2	KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:111	Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)	Cancer; Reproductive System Disease	-	0.2	KE:1614	Decrease, androgen receptor activation
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	0.27	KE:799	Increased, HIF-1 heterodimer
					KE:801	modulation, Unknown
					KE:802	Increased, HIF-1 alpha transcription
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary System Disease	Under Development	0.09	KE:277	Thyroid hormone synthesis, Decreased
AOP:131	Aryl hydrocarbon receptor activation leading to uroporphyria	Inherited Metabolic Disorder	WPHA/WNT Endorsed	0.33	KE:18	Activation, AhR
AOP:131		Inherited Metabolic Disorder	WPHA/WNT Endorsed	0.33	KE:850	Induction, CYP1A2/CYP1A5
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	0.14	KE:18	Activation, AhR
AOP:151	AhR activation leading to preeclampsia	Cardiovascular System Disease	Under Development	0.14	KE:18	Activation, AhR
AOP:155	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.17	KE:1002	Inhibition, Deiodinase 2
AOP:156	Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.17	KE:1002	Inhibition, Deiodinase 2
AOP:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive System Disease; Cancer	-	0.29	KE:1064	prepubertal increase, Estrogen receptor (ER) activity
AOP:167		Reproductive System Disease; Cancer	-	0.29	KE:1065	Activation, estrogen receptor alpha
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP:188		Unclassified	-	0.4	KE:1152	Inhibition, Iodotyrosine deiodinase (IYD)
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.17	KE:1002	Inhibition, Deiodinase 2
AOP:191	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:1153	Inhibition, Deiodinase 3
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1502	Histone deacetylase inhibition
AOP:212		Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1505	Cell cycle, disrupted
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-	0.17	KE:10008	Increased transcription for detoxification and repair mechanism
AOP:270	Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activity	Unclassified	-	0.12	KE:10008	Increased transcription for detoxification and repair mechanism
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural Tube Defect	-	0.2	KE:1502	Histone deacetylase inhibition
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.5	KE:1614	Decrease, androgen receptor activation
AOP:306		Unclassified	Under Development	0.5	KE:26	Antagonism, Androgen receptor
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	0.08	KE:18	Activation, AhR
AOP:314	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)	Immune System Disease; Musculoskeletal System Disease	Under Development	0.2	KE:1710	Binding to estrogen receptor (ER)-α in immune cells
AOP:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development	0.5	KE:1614	Decrease, androgen receptor activation
AOP:344		Unclassified	Under Development	0.5	KE:26	Antagonism, 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:1614	Decrease, androgen receptor activation
AOP:345			Under Development	0.33	KE:26	Antagonism, Androgen receptor
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine System Disease; Reproductive System Disease; Cancer	-	0.4	KE:1614	Decrease, androgen receptor activation
AOP:372	Androgen receptor antagonism leading to testicular cancer		-	0.4	KE:26	Antagonism, Androgen receptor
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	-	0.33	KE:18	Activation, AhR
AOP:416		Cancer	-	0.33	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	-	0.2	KE:18	Activation, AhR
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:1923	Altered gene expression, P53 dependent apoptosis pathway
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-	0.5	KE:18	Activation, AhR
AOP:420		Cancer	-	0.5	KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.22	KE:18	Activation, AhR
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.22	KE:1971	Increased, tumor growth
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic Disease; Cancer	Under Development	0.2	KE:1669	Increased, DNA damage and mutation
AOP:443		Thoracic Disease; Cancer	Under Development	0.2	KE:1554	Increase Chromosomal Aberrations
AOP:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive System Disease	-	0.12	KE:1065	Activation, estrogen receptor alpha
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary System Disease	-	0.17	KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
AOP:447		Urinary System Disease	-	0.17	KE:1770	Decrease, Mitochondrial membrane potential
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	0.17	KE:18	Activation, AhR
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.12	KE:18	Activation, AhR
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.33	KE:18	Activation, AhR
					KE:277	Thyroid hormone synthesis, Decreased
					KE:850	Induction, CYP1A2/CYP1A5
AOP:477	Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring	Physical Disorder	-	0.67	KE:1614	Decrease, androgen receptor activation
AOP:477		Physical Disorder	-	0.67	KE:26	Antagonism, Androgen receptor
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired Metabolic Disease	-	0.1	KE:2126	Estrogen receptor alpha inactivation
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.17	KE:18	Activation, AhR
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	-	0.12	KE:2126	Estrogen receptor alpha inactivation
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: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	-	0.2	KE:111	Agonism, Estrogen receptor
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive System Disease; Endocrine System Disease	-	0.17	KE:18	Activation, AhR

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:274	Histone deacetylase inhibition leads to impeded craniofacial development	Musculoskeletal System Disease	-	0.5	KE:1559	Facial cartilage structures are reduced in size and morphologically distorted
AOP:274		Musculoskeletal System Disease	-	0.5	KE:1502	Histone deacetylase inhibition
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:1559	Facial cartilage structures are reduced in size and morphologically distorted

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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_GLTED_hDIO2 - loss CCTE_GLTED_hDIO3 - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Deisenroth_AIME_384WELL_LUC_Active - gain CCTE_Deisenroth_AIME_384WELL_LUC_Inactive - gain CCTE_Deisenroth_AIME_384WELL_LUC_Shift - activatory ATG_ERE_CIS - activatory ATG_ERa_TRANS - gain TOX21_ERa_BLA_Agonist_ch2 - gain TOX21_ERa_BLA_Agonist_ratio - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_HIF1a_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	APR_HepG2_CellLoss_24hr - inhibitory CCTE_Simmons_CellTiterGLO_HEK293T - 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_HIF1a_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_IR1_CIS - inhibitory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_MitoMass_24hr - 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_rAR - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	Tanguay_ZF_120hpf_EYE_legacy - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_DT40_100_LUC - loss

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_MitoMembPot_24hr - inhibitory APR_HepG2_MitoMembPot_72hr - inhibitory TOX21_MMP_viability - loss

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_24hr - inhibitory

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_p53_BLA_p1_ch2 - gain

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_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	TOX21_HDAC_LUC_Antagonist - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006984 - Hypertrophy
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_Deisenroth_AIME_384WELL_LUC_Active - gain CCTE_Deisenroth_AIME_384WELL_LUC_Inactive - gain CCTE_Deisenroth_AIME_384WELL_LUC_Shift - activatory ATG_ERE_CIS - activatory ATG_ERa_TRANS - gain OT_ER_ERaERb_1440 - gain OT_ERa_GFPERaERE_0120 - gain TOX21_ERa_BLA_Agonist_ch2 - gain TOX21_ERa_LUC_VM7_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_PPARd_BLA_Agonist_ch2 - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	Tanguay_ZF_120hpf_BRAI_legacy - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006528 - Carcinoma, Hepatocellular
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006528 - Carcinoma, Hepatocellular
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	Tanguay_ZF_120hpf_YSE_legacy - gain Tanguay_ZF_120hpf_EYE_legacy - gain Tanguay_ZF_120hpf_SNOU_legacy - gain Tanguay_ZF_120hpf_JAW_legacy - gain Tanguay_ZF_120hpf_OTIC_legacy - gain Tanguay_ZF_120hpf_PE_legacy - gain Tanguay_ZF_120hpf_BRAI_legacy - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_CAR_LUC_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001749 - Urinary Bladder Neoplasms MESH:D006528 - Carcinoma, Hepatocellular MESH:D012509 - Sarcoma MESH:D012878 - Skin Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D008114 - Liver Neoplasms, Experimental MESH:D008113 - Liver Neoplasms
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_Deisenroth_AIME_384WELL_LUC_Active - gain CCTE_Deisenroth_AIME_384WELL_LUC_Inactive - gain CCTE_Deisenroth_AIME_384WELL_LUC_Shift - activatory ATG_ERa_TRANS - gain OT_ER_ERaERb_1440 - gain OT_ERa_GFPERaERE_0120 - gain TOX21_ERa_LUC_VM7_Agonist - gain

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_rAR - 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_HIF1a_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_HIF1a_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	LTEA_HepaRG_CYP1A2 - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_GLTED_hDIO2 - 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_ERa_LUC_VM7_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_GLTED_hDIO2 - loss CCTE_GLTED_hDIO3 - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_GLTED_hDIO3 - 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_RORE_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	OT_ER_ERaERb_1440 - gain OT_ERa_GFPERaERE_0120 - gain TOX21_ERa_LUC_VM7_Agonist - gain

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_p53Act_24hr - inhibitory

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	MESH:D006528 - Carcinoma, Hepatocellular
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D048629 - Micronuclei, Chromosome-Defective
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_Deisenroth_AIME_384WELL_LUC_Shift - activatory

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

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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.

Benz(a)anthracene

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