TICToK | Tattoo Ink Chemicals and associated Toxicities Knowledgebase

2-Naphthylamine

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: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	0.1	KE:1392	Oxidative Stress
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive System Disease	Under Review	0.12	KE:289	Decrease, Translocator protein (TSPO)
AOP:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive System Disease	-	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
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:107	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Cancer; Gastrointestinal System Disease	Under Review	0.2	KE:1214	Altered gene expression specific to CAR activation, Hepatocytes
AOP:108	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.17	KE:768	Increase, Cytotoxicity
AOP: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: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:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.25	KE:155	Inadequate DNA repair
AOP:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal System Disease	Under Review	0.11	KE:1494	Leukocyte recruitment/activation
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:1497	Increased, recruitment of inflammatory cells
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP: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:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	0.17	KE:295	Induction, Upregulation of glucuronyltransferase activity
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.17	KE:1505	Cell cycle, disrupted
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal System Disease	WPHA/WNT Endorsed	0.2	KE:1392	Oxidative Stress
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous System Disease	-	0.14	KE:1392	Oxidative Stress
AOP:268	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling	Unclassified	Under Development	0.25	KE:2072	Increase, Mitochondrial swelling
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.14	KE:155	Inadequate DNA repair
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:293	Increased DNA damage leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.11	KE:1494	Leukocyte recruitment/activation
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.11	KE:1494	Leukocyte recruitment/activation
AOP:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic Disease; Chromosomal Disease	WPHA/WNT Endorsed	0.2	KE:155	Inadequate DNA repair
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	0.29	KE:1669	Increased, DNA damage and mutation
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.29	KE:1497	Increased, recruitment of inflammatory cells
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.4	KE:1614	Decrease, androgen receptor activation
AOP:305		Unclassified	Under Development	0.4	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.5	KE:1614	Decrease, androgen receptor activation
AOP:306		Unclassified	Under Development	0.5	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.2	KE:155	Inadequate DNA repair
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	-	0.17	KE:1505	Cell cycle, disrupted
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-	0.2	KE:1505	Cell cycle, disrupted
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: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:1614	Decrease, androgen receptor activation
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:1614	Decrease, androgen receptor activation
AOP:372	Androgen receptor antagonism leading to testicular cancer		-	0.4	KE:286	Altered, Transcription of genes by the androgen receptor
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:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	0.2	KE:1497	Increased, recruitment of inflammatory cells
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:1643	Altered, Visual function
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.25	KE:1669	Increased, DNA damage and mutation
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.25	KE:1497	Increased, recruitment of inflammatory cells
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic System Disease; Cancer	-	0.09	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:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.08	KE:1392	Oxidative Stress
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-	0.11	KE:1392	Oxidative Stress
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.2	KE:18	Activation, AhR
					KE:165	Activation, Long term AHR receptor driven direct and indirect gene expression changes
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1392	Oxidative Stress
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.06	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	-	0.22	KE:1669	Increased, DNA damage and mutation
AOP:451		Cancer	-	0.22	KE:1497	Increased, recruitment of inflammatory cells
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.09	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	-	0.08	KE:1392	Oxidative Stress
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited Metabolic Disorder	-	0.33	KE:277	Thyroid hormone synthesis, Decreased
AOP:457		Inherited Metabolic Disorder	-	0.33	KE:1392	Oxidative Stress
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.09	KE:1392	Oxidative Stress
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous System Disease	-	0.05	KE:1392	Oxidative Stress
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.12	KE:748	Increased, Estrogen receptor (ER) activity
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-	0.12	KE:1497	Increased, recruitment of inflammatory cells
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal System Disease	-	0.08	KE:1392	Oxidative Stress
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular System Disease	Under Review	0.12	KE:1392	Oxidative Stress
AOP:477	Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring	Physical Disorder	-	0.33	KE:1614	Decrease, androgen receptor activation
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.2	KE:155	Inadequate DNA repair
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.2	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	0.14	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.14	KE:1392	Oxidative Stress
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental Disorder Of Mental Health	Under Review	0.12	KE:1392	Oxidative Stress
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive Disorder	-	0.14	KE:1392	Oxidative Stress
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired Metabolic Disease	-	0.1	KE:1497	Increased, recruitment of inflammatory cells
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:1392	Oxidative Stress
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous System Disease	-	0.25	KE:1392	Oxidative Stress
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.2	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	-	0.14	KE:1392	Oxidative Stress
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular System Disease	-	0.1	KE:1392	Oxidative Stress
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular System Disease	-	0.06	KE:1392	Oxidative Stress
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
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	0.14	KE:1392	Oxidative Stress
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	0.17	KE:1392	Oxidative Stress
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental Disorder Of Mental Health	-	0.11	KE:1392	Oxidative Stress
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-	0.11	KE:1392	Oxidative Stress
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular System Disease	-	0.08	KE:1392	Oxidative Stress

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:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	0.2	KE:1001	Increased, Developmental Defects
AOP:466	Doda decarboxylase leading to mortality	Integumentary System Disease	-	0.11	KE:2055	Increase, pigmentation
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: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: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:295	Induction, Upregulation of glucuronyltransferase activity
AOP:8		Nervous System Disease	Under Development	0.22	KE:239	Activation, Pregnane-X receptor, NR1l2
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	0.1	KE:25	Agonism, Androgen receptor
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:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	WPHA/WNT Endorsed	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:42		Cognitive Disorder	WPHA/WNT Endorsed	0.25	KE:279	Thyroperoxidase, Inhibition
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:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	Under Development	0.25	KE:25	Agonism, Androgen receptor
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:119		Cancer; Endocrine System Disease	-	0.29	KE:279	Thyroperoxidase, Inhibition
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:151	AhR activation leading to preeclampsia	Cardiovascular System Disease	Under Development	0.14	KE:18	Activation, AhR
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:159		Unclassified	WPHA/WNT Endorsed	0.25	KE:279	Thyroperoxidase, Inhibition
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:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.5	KE:277	Thyroid hormone synthesis, Decreased
AOP:175		Unclassified	-	0.5	KE:279	Thyroperoxidase, Inhibition
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	0.4	KE:277	Thyroid hormone synthesis, Decreased
AOP:271		Unclassified	Under Development	0.4	KE:279	Thyroperoxidase, Inhibition
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:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	0.38	KE:277	Thyroid hormone synthesis, Decreased
					KE:1643	Altered, Visual function
					KE:279	Thyroperoxidase, Inhibition
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development	0.38	KE:277	Thyroid hormone synthesis, Decreased
					KE:1643	Altered, Visual function
					KE:279	Thyroperoxidase, Inhibition
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development	0.38	KE:277	Thyroid hormone synthesis, Decreased
					KE:1643	Altered, Visual function
					KE:279	Thyroperoxidase, Inhibition
AOP:376	Androgen receptor agonism leading to male-biased sex ratio	Unclassified	WPHA/WNT Endorsed	0.25	KE:25	Agonism, 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	-	0.33	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	-	0.6	KE:18	Activation, AhR
					KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
					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	-	0.4	KE:18	Activation, AhR
AOP:418		Respiratory System Disease	-	0.4	KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory System Disease	-	0.25	KE:18	Activation, AhR
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: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:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.11	KE:18	Activation, AhR
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:155	Inadequate DNA repair
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	-	0.25	KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
					KE:1770	Decrease, Mitochondrial membrane potential
					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:295	Induction, Upregulation of glucuronyltransferase activity
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.44	KE:18	Activation, AhR
					KE:277	Thyroid hormone synthesis, Decreased
					KE:1392	Oxidative Stress
					KE:850	Induction, CYP1A2/CYP1A5
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.11	KE:1392	Oxidative Stress
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.17	KE:18	Activation, AhR
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive System Disease; Cancer	-	0.22	KE:25	Agonism, Androgen receptor
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive System Disease; Cancer	-	0.22	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	0.2	KE:25	Agonism, Androgen receptor
AOP:496		Unclassified	-	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
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: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:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.08	KE:2216	Binding of antagonist to thyroid hormone 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	-	0.2	KE:111	Agonism, Estrogen receptor
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	-	0.17	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: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: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: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

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	TOX21_DT40_657_LUC - 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_ARE_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	NVS_MP_hPBR - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CEETOX_H295R_ANDR - inhibitory

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_THRSP - inhibitory

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	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CEETOX_H295R_MTT_cell_viability - inhibitory

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	BSK_SAg_Eselectin - 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_SAg_Eselectin - 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_UGT1A1 - 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_CellCycleArrest_72hr - inhibitory

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_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	CEETOX_H295R_ANDR - inhibitory

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	-
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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_Ahr_CIS - activatory TOX21_AhR_LUC_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	ATG_Ahr_CIS - activatory TOX21_AhR_LUC_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_Deisenroth_AIME_384WELL_LUC_Active - 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	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	CCTE_Padilla_ZF_144hpf_TERATOSCORE - gain Tanguay_ZF_120hpf_YSE_legacy - gain Tanguay_ZF_120hpf_AXIS_legacy - gain Tanguay_ZF_120hpf_EYE_legacy - gain Tanguay_ZF_120hpf_SNOU_legacy - gain Tanguay_ZF_120hpf_JAW_legacy - gain Tanguay_ZF_120hpf_PE_legacy - gain Tanguay_ZF_120hpf_BRAI_legacy - gain Tanguay_ZF_120hpf_TR_legacy - gain Tanguay_ZF_120hpf_ActivityScore_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	Tanguay_ZF_120hpf_PIG_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	CCTE_Deisenroth_AIME_384WELL_LUC_Active - 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_PXR_LUC_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	ACEA_AR_agonist_80hr - 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_Simmons_AUR_TPO - loss

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	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_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_AhR_LUC_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_ARE_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	LTEA_HepaRG_THRSP - inhibitory

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_ActivityScore_legacy - gain

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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.

2-Naphthylamine

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