TICToK | Tattoo Ink Chemicals and associated Toxicities Knowledgebase

Naphthalene

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:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous System Disease	Under Development	0.11	KE:295	Induction, Upregulation of glucuronyltransferase activity
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	0.1	KE:55	Increase, Cell injury/death
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:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal System Disease	Under Development	0.12	KE:288	Activation of specific nuclear receptors, Transcriptional change
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal System Disease	Under Development	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal System Disease	WPHA/WNT Endorsed	0.14	KE:55	Increase, Cell injury/death
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory System Disease	Under Development	0.2	KE:272	Activation/Proliferation, T-cells
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary System Disease	WPHA/WNT Endorsed	0.2	KE:272	Activation/Proliferation, T-cells
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal System Disease	Under Review	0.2	KE:854	Alterations, Cellular proliferation / hyperplasia
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: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: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: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:716	Increase, cell proliferation (hepatocytes)
AOP:108	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.17	KE:768	Increase, Cytotoxicity
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory System Disease	-	0.2	KE:734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.14	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive System Disease; Cancer	-	0.17	KE:111	Agonism, Estrogen receptor
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:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	Under Development	0.25	KE:716	Increase, cell proliferation (hepatocytes)
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.25	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.14	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
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: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: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:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	0.17	KE:295	Induction, Upregulation of glucuronyltransferase activity
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive System Disease	-	0.12	KE:1281	Increased, DNA Damage-Repair
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal System Disease	-	0.12	KE:1287	Glutathione synthesis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.17	KE:1505	Cell cycle, disrupted
AOP:245	Reduction in photophosphorylation leading to growth inhibition in aquatic plants	Unclassified	-	0.09	KE:40	Decrease, Mitochondrial ATP production
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary System Disease	Under Development	0.2	KE:40	Decrease, Mitochondrial ATP production
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	0.5	KE:1821	Decrease, Cell proliferation
AOP:263		Unclassified	WPHA/WNT Endorsed	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:264		Unclassified	Under Development	0.5	KE:55	Increase, Cell injury/death
AOP:265	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium	Unclassified	Under Development	0.25	KE:55	Increase, Cell injury/death
AOP:266	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity	Unclassified	Under Development	0.33	KE:1771	Decrease, Adenosine triphosphate pool
AOP:266		Unclassified	Under Development	0.33	KE:55	Increase, Cell injury/death
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:55	Increase, Cell injury/death
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:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	0.5	KE:1821	Decrease, Cell proliferation
AOP:286		Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:287		Unclassified	-	0.5	KE:1825	Increase, Cell death
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	0.5	KE:1821	Decrease, Cell proliferation
AOP:290		Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:291		Unclassified	-	0.5	KE:1825	Increase, Cell death
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.11	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	0.11	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	0.2	KE:155	Inadequate DNA repair
AOP:305	5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:306	Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	Unclassified	Under Development	0.25	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.2	KE:155	Inadequate DNA repair
AOP:324	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death	Unclassified	-	0.25	KE:55	Increase, Cell injury/death
AOP:325	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death	Unclassified	-	0.25	KE:55	Increase, Cell injury/death
AOP:326	Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death	Unclassified	-	0.25	KE:55	Increase, Cell injury/death
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	0.2	KE:1771	Decrease, Adenosine triphosphate pool
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	0.2	KE:1771	Decrease, Adenosine triphosphate pool
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	-	0.4	KE:1821	Decrease, Cell proliferation
AOP:333		Unclassified	-	0.4	KE:1771	Decrease, Adenosine triphosphate pool
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:344	Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspring	Unclassified	Under Development	0.25	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine System Disease; Reproductive System Disease; Reproductive System Disease	Under Development	0.17	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:368	Cytochrome oxidase inhibition leading to increased nasal lesions	Unclassified	-	0.33	KE:1825	Increase, Cell death
AOP:372	Androgen receptor antagonism leading to testicular cancer	Endocrine System Disease; Reproductive System Disease; Cancer	-	0.2	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive System Disease	-	0.12	KE:40	Decrease, Mitochondrial ATP production
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	-	0.12	KE:870	Increase, Cell Proliferation
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:1607	Increase, Necrosis
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: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:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic Disease; Cancer	Under Development	0.2	KE:1554	Increase Chromosomal Aberrations
AOP:443		Thoracic Disease; Cancer	Under Development	0.2	KE:155	Inadequate DNA repair
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.05	KE:1250	Decrease, Lung function
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary System Disease	-	0.08	KE:1097	Occurrence, renal proximal tubular necrosis
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.12	KE:295	Induction, Upregulation of glucuronyltransferase activity
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	0.11	KE:1821	Decrease, Cell proliferation
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous System Disease	-	0.05	KE:1825	Increase, Cell death
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:1825	Increase, Cell death
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.22	KE:1825	Increase, Cell death
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.22	KE:1097	Occurrence, renal proximal tubular necrosis
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.2	KE:870	Increase, Cell Proliferation
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: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:55	Increase, Cell injury/death
AOP:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular System Disease; Thoracic Disease	Under Development	0.2	KE:40	Decrease, Mitochondrial ATP production
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.14	KE:1825	Increase, Cell death
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	0.17	KE:1821	Decrease, Cell proliferation
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.17	KE:55	Increase, Cell injury/death
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive System Disease; Cancer	-	0.22	KE:854	Alterations, Cellular proliferation / hyperplasia
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	-	0.1	KE:286	Altered, Transcription of genes by the androgen receptor
AOP:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal System Disease	-	0.2	KE:55	Increase, Cell injury/death
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	0.09	KE:40	Decrease, Mitochondrial ATP production
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: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:148	EGFR Activation Leading to Decreased Lung Function	Respiratory System Disease	Under Development	0.25	KE:1250	Decrease, Lung function
AOP:205	AOP from chemical insult to cell death	Unclassified	-	0.17	KE:1263	Necrosis
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.43	KE:870	Increase, Cell Proliferation
					KE:1556	Increase, lung cancer
					KE:155	Inadequate DNA repair
AOP:302	Lung surfactant function inhibition leading to decreased lung function	Respiratory System Disease	Under Development	0.2	KE:1250	Decrease, Lung function
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.29	KE:870	Increase, Cell Proliferation
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.29	KE:1670	Lung cancer
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory System Disease	-	0.25	KE:1250	Decrease, Lung function
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-	0.17	KE:1670	Lung cancer
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-	0.2	KE:1670	Lung cancer
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory System Disease	-	0.4	KE:1250	Decrease, Lung function
AOP:418		Respiratory System Disease	-	0.4	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:1250	Decrease, Lung function
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:870	Increase, Cell Proliferation
AOP:420		Cancer	-	0.5	KE:1670	Lung cancer
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory System Disease	-	0.17	KE:1250	Decrease, Lung function
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory System Disease	-	0.17	KE:1250	Decrease, Lung function
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.22	KE:870	Increase, Cell Proliferation
AOP:451		Cancer	-	0.22	KE:1670	Lung 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:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive System Disease	-	0.12	KE:1065	Activation, estrogen receptor alpha
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: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: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	-	0.2	KE:111	Agonism, Estrogen receptor

No associated AOPs with Level of Relevance 5

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	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_CellLoss_72hr - inhibitory

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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_HNF6_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_HNF6_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation
CTD - Disease	MESH:D006965 - Hyperplasia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO: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: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	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_CellLoss_72hr - inhibitory

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 GO:0008284 - positive 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	ATG_ERa_TRANS - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	GO:0008283 - cell population proliferation GO:0008284 - positive 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	ATG_ERa_TRANS - gain

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

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

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_CellLoss_72hr - inhibitory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - cell population proliferation GO:0008284 - positive 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	MESH:D009336 - Necrosis
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

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	MESH:D055371 - Acute Lung Injury
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D058186 - Acute Kidney Injury
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

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

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D009336 - Necrosis
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

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

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	APR_HepG2_p53Act_72hr - activatory

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

Naphthalene

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

Glossary of Terms

DISCLAIMER

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

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

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