Pyrene

Pyrene



Associated High Confidence AOPs
For more information or term definitions, please refer to HELP page.

Navigate to: Level 1Level 2Level 3Level 5

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:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE:155
Inadequate DNA repair
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.12KE:288
Activation of specific nuclear receptors, Transcriptional change
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:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.4KE:854
Alterations, Cellular proliferation / hyperplasia
KE:139
N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
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:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-0.12KE:664
Overwhelmed, Mitochondrial DNA repair mechanisms
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:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.17KE:768
Increase, Cytotoxicity
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: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:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:850
Induction, CYP1A2/CYP1A5
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.29KE:768
Increase, Cytotoxicity
KE: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-0.29KE:1067
Proliferation/Clonal Expansion, aberrant basal cells
KE:1065
Activation, estrogen receptor alpha
AOP:194Hepatic nuclear receptor activation leading to altered amphibian metamorphosisUnclassified-0.17KE:295
Induction, Upregulation of glucuronyltransferase activity
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.25KE:1281
Increased, DNA Damage-Repair
KE:1262
Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.17KE: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:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.25KE:1821
Decrease, Cell proliferation
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine System Disease-0.12KE:1614
Decrease, androgen receptor activation
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:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:155
Inadequate DNA repair
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.14KE:870
Increase, Cell Proliferation
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.4KE:1614
Decrease, androgen receptor activation
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.2KE:155
Inadequate DNA repair
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-0.2KE:1769
Increase, Body fluid overload
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-0.2KE:1770
Decrease, Mitochondrial membrane potential
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:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive System Disease-0.12KE:1770
Decrease, Mitochondrial membrane potential
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155
Inadequate DNA repair
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:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.25KE:1262
Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:870
Increase, Cell Proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.18KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.11KE: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 Development0.11KE:1973
Increased, estrogens
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 Development0.1KE:155
Inadequate DNA repair
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.05KE:1262
Apoptosis
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.11KE:870
Increase, Cell Proliferation
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.09KE:1262
Apoptosis
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:295
Induction, Upregulation of glucuronyltransferase activity
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:850
Induction, CYP1A2/CYP1A5
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.22KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748
Increased, Estrogen receptor (ER) activity
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.11KE:1097
Occurrence, renal proximal tubular necrosis
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.2KE:870
Increase, Cell Proliferation
KE:155
Inadequate DNA repair
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.33KE:1821
Decrease, Cell proliferation
KE:1262
Apoptosis
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.22KE:854
Alterations, Cellular proliferation / hyperplasia
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-0.1KE:286
Altered, Transcription of genes by the androgen receptor
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:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.1KE:2165
Activation of PPAR
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
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.17KE: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:43Disruption of VEGFR Signaling Leading to Developmental DefectsUnclassifiedWPHA/WNT Endorsed0.2KE:1001
Increased, Developmental Defects
AOP:139Alkylation of DNA leading to cancer 1Cancer-0.5KE:885
Increase, Cancer
KE:155
Inadequate DNA repair
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263
Necrosis
KE:1262
Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.4KE:1393
Hepatocytotoxicity
KE:1395
Liver Cancer
AOP:274Histone deacetylase inhibition leads to impeded craniofacial developmentMusculoskeletal System Disease-0.25KE:1559
Facial cartilage structures are reduced in size and morphologically distorted
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.17KE:1559
Facial cartilage structures are reduced in size and morphologically distorted
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:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-0.33KE:1065
Activation, estrogen receptor alpha
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
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-0.2KE: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:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous System DiseaseUnder Development0.22KE:295
Induction, Upregulation of glucuronyltransferase activity
KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.12KE:227
Activation, PPARα
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.4KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.4KE:227
Activation, PPARα
KE:716
Increase, cell proliferation (hepatocytes)
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:245
Activation, PXR/SXR
AOP:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1614
Decrease, androgen receptor activation
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.5KE:786
Increase, Cytotoxicity (hepatocytes)
KE:787
Increase, Regenerative cell proliferation (hepatocytes)
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:314Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)Immune System Disease; Musculoskeletal System DiseaseUnder Development0.2KE:1710
Binding to estrogen receptor (ER)-α in immune cells
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-0.17KE:227
Activation, PPARα
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine System Disease; Reproductive System Disease; Reproductive System DiseaseUnder Development0.5KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine System Disease; Reproductive System Disease; Cancer-0.6KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
KE:286
Altered, Transcription of genes by the androgen receptor
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive System Disease-0.25KE:1987
Decreased, Androgen and Progestin
KE:1065
Activation, estrogen receptor alpha
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.17KE:1770
Decrease, Mitochondrial membrane potential
KE:1097
Occurrence, renal proximal tubular necrosis
AOP:477Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspringPhysical Disorder-0.67KE:1614
Decrease, androgen receptor activation
KE:26
Antagonism, Androgen receptor
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive System Disease; CancerUnder Review0.17KE:1065
Activation, estrogen receptor alpha
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.2KE:2201
Agonism, Retinoic acid receptor
AOP:523Retinoic acid receptor agonism during neurodevelopment leading to microcephalyCongenital Nervous System Abnormality; Nervous System Disease-0.2KE:2201
Agonism, Retinoic acid receptor
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.15KE:2220
Antagonism, Glucocorticoid hormone receptor
KE:2217
Binding of antagonist to glucocorticoid hormone receptor
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2201
Agonism, Retinoic acid receptor
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:545Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesisUnclassified-0.2KE:239
Activation, Pregnane-X receptor, NR1l2
AOP:548Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expressionUnclassified-0.2KE:239
Activation, Pregnane-X receptor, NR1l2

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
?
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.