Dibenz[a,h]anthracene

Dibenz[a,h]anthracene



Associated High Confidence AOPs
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Associated AOPs with Level of Relevance 1
AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.2KE:716
Increase, cell proliferation (hepatocytes)
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory System DiseaseUnder Development0.2KE:272
Activation/Proliferation, T-cells
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.2KE:272
Activation/Proliferation, T-cells
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.14KE:496
Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.17KE:710
Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.4KE:1214
Altered gene expression specific to CAR activation, Hepatocytes
KE:716
Increase, cell proliferation (hepatocytes)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory System Disease-0.2KE:734
Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:739
Increase, Hypertrophy and proliferation (follicular cell)
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.17KE:111
Agonism, Estrogen receptor
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-0.17KE:778
Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-0.2KE:781
Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.25KE:710
Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System DiseaseUnder Development0.25KE:716
Increase, cell proliferation (hepatocytes)
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.25KE:787
Increase, Regenerative cell proliferation (hepatocytes)
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:739
Increase, Hypertrophy and proliferation (follicular cell)
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary System Disease-0.2KE:795
Increase, Regenerative cell proliferation (urothelial cells)
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.14KE:870
Increase, Cell Proliferation
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive System Disease-0.17KE:1042
Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.14KE:1067
Proliferation/Clonal Expansion, aberrant basal cells
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.12KE:1262
Apoptosis
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed0.25KE:1821
Decrease, Cell proliferation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.2KE:1821
Decrease, Cell proliferation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.25KE:1821
Decrease, Cell proliferation
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.25KE:1821
Decrease, Cell proliferation
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1182
Increase, Cell Proliferation (Epithelial Cells)
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1182
Increase, Cell Proliferation (Epithelial Cells)
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.17KE:1821
Decrease, Cell proliferation
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1821
Decrease, Cell proliferation
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.2KE:1821
Decrease, Cell proliferation
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary System Disease-0.2KE:795
Increase, Regenerative cell proliferation (urothelial cells)
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular System DiseaseUnder Development0.14KE:1845
Coagulation
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.12KE:1821
Decrease, Cell proliferation
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.12KE:870
Increase, Cell Proliferation
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.17KE:1607
Increase, Necrosis
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.09KE:870
Increase, Cell Proliferation
AOP:441Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiationCongenital Nervous System Abnormality; Nervous System Disease-0.14KE:1262
Apoptosis
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.2KE:1554
Increase Chromosomal Aberrations
KE:112
Antagonism, Estrogen receptor
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.15KE:18
Activation, AhR
KE:165
Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:1262
Apoptosis
AOP:449Ceramide synthase inhibition leading to neural tube defectsNeural Tube Defect-0.14KE:1502
Histone deacetylase inhibition
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.09KE:1262
Apoptosis
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.33KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
KE:2043
Decrease, Sonic Hedgehog second messenger production
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748
Increased, Estrogen receptor (ER) activity
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.1KE:870
Increase, Cell Proliferation
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.5KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
KE:2043
Decrease, Sonic Hedgehog second messenger production
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.11KE:854
Alterations, Cellular proliferation / hyperplasia
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-0.14KE:1262
Apoptosis
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.11KE:1262
Apoptosis
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.11KE:1262
Apoptosis

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:139Alkylation of DNA leading to cancer 1Cancer-0.25KE:885
Increase, Cancer
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263
Necrosis
KE:1262
Apoptosis
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:870
Increase, Cell Proliferation
KE:1556
Increase, lung cancer
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal System DiseaseUnder Review0.17KE:1651
Treatment-resistant gastric cancer
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.29KE:870
Increase, Cell Proliferation
KE:1670
Lung cancer
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.22KE:870
Increase, Cell Proliferation
KE:1670
Lung cancer
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.18KE:1262
Apoptosis
KE:2034
liver dysfunction
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder Development0.2KE:885
Increase, Cancer
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.2KE:885
Increase, Cancer
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.2KE:885
Increase, Cancer
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.17KE:885
Increase, Cancer
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-0.2KE: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:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.2KE:18
Activation, AhR
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.17KE:112
Antagonism, Estrogen receptor
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.4KE:854
Alterations, Cellular proliferation / hyperplasia
KE:165
Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:18
Activation, AhR
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.14KE:18
Activation, AhR
AOP:151AhR activation leading to preeclampsiaCardiovascular System DiseaseUnder Development0.14KE:18
Activation, AhR
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.33KE:1262
Apoptosis
KE:1502
Histone deacetylase inhibition
AOP:274Histone deacetylase inhibition leads to impeded craniofacial developmentMusculoskeletal System Disease-0.25KE:1502
Histone deacetylase inhibition
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.2KE:1502
Histone deacetylase inhibition
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.08KE:18
Activation, AhR
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:18
Activation, AhR
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:18
Activation, AhR
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.4KE:18
Activation, AhR
KE:17
Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.5KE:18
Activation, AhR
KE:1262
Apoptosis
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.33KE:18
Activation, AhR
KE:1971
Increased, tumor growth
KE:1262
Apoptosis
AOP:440Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasiaBenign Neoplasm; Endocrine System Disease; Reproductive System Disease; Reproductive System Disease; Cancer; Endocrine System DiseaseUnder Development0.22KE:1973
Increased, estrogens
KE:1046
Suppression, Estrogen receptor (ER) activity
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.08KE:1917
Altered gene expression, NRF2 dependent antioxidant pathway
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.17KE:18
Activation, AhR
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.17KE:18
Activation, AhR
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:18
Activation, AhR
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:18
Activation, AhR
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.1KE:2126
Estrogen receptor alpha inactivation
AOP:494AhR activation leading to liver fibrosisGastrointestinal System Disease-0.17KE:18
Activation, AhR
AOP:497ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndromeInherited Metabolic Disorder; Disease Of Metabolism-0.12KE:2126
Estrogen receptor alpha inactivation
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:111
Agonism, Estrogen receptor
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:111
Agonism, Estrogen receptor
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.33KE:18
Activation, AhR
KE:1262
Apoptosis

Associated AOPs with Level of Relevance 5
AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.33KE:18
Activation, AhR
KE:1670
Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.6KE:18
Activation, AhR
KE:17
Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1670
Lung cancer
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-1.0KE:18
Activation, AhR
KE:1917
Altered gene expression, NRF2 dependent antioxidant pathway
KE:1670
Lung cancer
KE:870
Increase, Cell Proliferation
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
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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.