TICToK | Tattoo Ink Chemicals and associated Toxicities Knowledgebase

Benzo(b)fluoranthene

Associated curated AOPs from AOP-Wiki

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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: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:17	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.2	KE:55	Increase, Cell injury/death
AOP:17		Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.2	KE:1392	Oxidative Stress
AOP:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal System Disease	WPHA/WNT Endorsed	0.14	KE:55	Increase, Cell injury/death
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:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive System Disease	-	0.14	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive System Disease; Cancer	-	0.17	KE:111	Agonism, Estrogen receptor
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	0.1	KE:799	Increased, HIF-1 heterodimer
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:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal System Disease	Under Review	0.22	KE:1494	Leukocyte recruitment/activation
AOP:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal System Disease	Under Review	0.22	KE:55	Increase, Cell injury/death
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: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: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: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:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development	0.25	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	0.17	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	0.5	KE:55	Increase, Cell injury/death
AOP:268		Unclassified	Under Development	0.5	KE:2072	Increase, Mitochondrial swelling
AOP:277	Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response	Immune System Disease	WPHA/WNT Endorsed	0.25	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-	0.25	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-	0.25	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	-	0.25	KE:1821	Decrease, Cell proliferation
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	0.25	KE:1825	Increase, Cell death
AOP:288	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)	Endocrine System Disease	-	0.12	KE: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:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	0.25	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: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: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: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: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:368	Cytochrome oxidase inhibition leading to increased nasal lesions	Unclassified	-	0.33	KE:1825	Increase, Cell death
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular System Disease	Under Development	0.14	KE:1845	Coagulation
AOP:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	0.2	KE:1497	Increased, recruitment of inflammatory cells
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:1497	Increased, recruitment of inflammatory cells
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: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: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	0.1	KE:1554	Increase Chromosomal Aberrations
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:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive System Disease	-	0.12	KE:1987	Decreased, Androgen and Progestin
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: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	-	0.17	KE:1392	Oxidative Stress
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	-	0.11	KE:1825	Increase, Cell death
AOP:464		Nervous System Disease	-	0.11	KE:1392	Oxidative Stress
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.12	KE:748	Increased, Estrogen receptor (ER) activity
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-	0.25	KE:1497	Increased, recruitment of inflammatory cells
AOP:468		Unclassified	-	0.25	KE:1825	Increase, Cell death
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:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.1	KE:1392	Oxidative Stress
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular System Disease; Thoracic Disease	Under Development	0.29	KE:55	Increase, Cell injury/death
AOP:479		Cardiovascular System Disease; Thoracic Disease	Under Development	0.29	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:1825	Increase, Cell death
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:1392	Oxidative Stress
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental Disorder Of Mental Health	Under Review	0.12	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:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental Disorder Of Mental Health	-	0.18	KE:2123	decreased, Bcl-2 expression
AOP:490		Developmental Disorder Of Mental Health	-	0.18	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: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: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	-	0.2	KE:2165	Activation of PPAR
AOP:510		Cardiovascular System Disease	-	0.2	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:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	0.14	KE:1392	Oxidative Stress
AOP:530	Endocytotic lysosomal uptake leads to intestinal barrier disruption	Gastrointestinal System Disease	-	0.2	KE:55	Increase, Cell injury/death
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental Disorder Of Mental Health	-	0.22	KE:2233	Decreased, ERαβ heterodimers
AOP:535		Developmental Disorder Of Mental Health	-	0.22	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
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:107	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Cancer; Gastrointestinal System Disease	Under Review	0.4	KE:719	Increase, hepatocellular adenomas and carcinomas
AOP:107		Cancer; Gastrointestinal System Disease	Under Review	0.4	KE:716	Increase, cell proliferation (hepatocytes)
AOP: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:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive System Disease	-	0.17	KE:330	Decrease, Fertility
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.25	KE:885	Increase, Cancer
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	0.14	KE:1556	Increase, lung cancer
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.29	KE:1497	Increased, recruitment of inflammatory cells
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.29	KE:1670	Lung cancer
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.22	KE:1497	Increased, recruitment of inflammatory cells
AOP:451		Cancer	-	0.22	KE:1670	Lung cancer
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.18	KE:1392	Oxidative Stress
AOP:463		Gastrointestinal System Disease	-	0.18	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:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.4	KE:885	Increase, Cancer
AOP:505		Cancer	-	0.4	KE:1392	Oxidative Stress
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	-	0.33	KE:885	Increase, Cancer
AOP:534		Cancer	-	0.33	KE:1392	Oxidative Stress
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	0.2	KE:885	Increase, Cancer

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:18	PPARα activation in utero leading to impaired fertility in males	Reproductive System Disease	Under Review	0.12	KE:227	Activation, PPARα
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: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: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:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	0.17	KE:227	Activation, PPARα
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: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:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory System Disease	-	0.6	KE:18	Activation, AhR
					KE:17	Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
					KE:1825	Increase, Cell death
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: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	0.22	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: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:202	Inhibition, Nuclear factor kappa B (NF-kB)
					KE:1392	Oxidative Stress
AOP:455	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial development	Musculoskeletal System Disease	Under Review	0.17	KE:18	Activation, AhR
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:850	Induction, CYP1A2/CYP1A5
					KE:1392	Oxidative Stress
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.22	KE:1392	Oxidative Stress
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.22	KE:1825	Increase, Cell death
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:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.33	KE:18	Activation, AhR
AOP:494	AhR activation leading to liver fibrosis	Gastrointestinal System Disease	-	0.33	KE:55	Increase, Cell injury/death
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.15	KE:2220	Antagonism, Glucocorticoid hormone receptor
AOP:525		Developmental Disorder Of Mental Health	-	0.15	KE:2217	Binding of antagonist to glucocorticoid 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: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:19	Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)	Reproductive System Disease	-	0.4	KE:26	Antagonism, Androgen receptor
AOP:19		Reproductive System Disease	-	0.4	KE:337	N/A, Impairment of reproductive capacity
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal System Disease	Under Development	0.6	KE:719	Increase, hepatocellular adenomas and carcinomas
					KE:227	Activation, PPARα
					KE:716	Increase, cell proliferation (hepatocytes)
AOP:108	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.5	KE:768	Increase, Cytotoxicity
					KE:719	Increase, hepatocellular adenomas and carcinomas
					KE:724	Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme
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:1670	Lung cancer
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:1670	Lung cancer
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-	0.75	KE:18	Activation, AhR
					KE:1917	Altered gene expression, NRF2 dependent antioxidant pathway
					KE:1670	Lung cancer

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	APR_HepG2_CellLoss_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	TOX21_ARE_BLA_Agonist_ratio - gain

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_ERE_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	APR_HepG2_CellLoss_24hr - inhibitory APR_HepG2_CellLoss_72hr - inhibitory ACEA_AR_antagonist_AUC_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	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	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_CellCycleArrest_72hr - 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 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	LTEA_HepaRG_NFKB1 - 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_CellLoss_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	ACEA_AR_antagonist_80hr - loss

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	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_ERE_CIS - activatory

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	CEETOX_H295R_PROG - 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	ATG_ERE_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_BCL2 - 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_PPRE_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects expression of estrogen receptor-alpha (ER-alpha)
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D012509 - Sarcoma MESH:D002471 - Cell Transformation, Neoplastic MESH:D006528 - Carcinoma, Hepatocellular MESH:D012878 - Skin Neoplasms 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	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	ATG_PPRE_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	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	ACEA_AR_antagonist_80hr - 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_AhR_LUC_Agonist - 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	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_NRF2_ARE_CIS - activatory 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	CEETOX_H295R_11DCORT - inhibitory CEETOX_H295R_DOC - inhibitory

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_11DCORT - inhibitory CEETOX_H295R_DOC - inhibitory

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

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	LTEA_HepaRG_PDK4 - inhibitory

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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.

Benzo(b)fluoranthene

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