Carbon

Carbon



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:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-0.2KE:1264
Increase, Nuclear receptor E75b gene expression
KE:1265
Increase, Fushi tarazu factor-1 gene expression
AOP:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive System Disease; Endocrine System Disease; Reproductive System DiseaseUnder Review0.4KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous System DiseaseUnder Development0.11KE:756
Hippocampal gene expression, Altered
AOP:12Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in agingNervous System Disease; Developmental Disorder Of Mental HealthWPHA/WNT Endorsed0.12KE:381
Reduced levels of BDNF
AOP:13Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilitiesDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:381
Reduced levels of BDNF
AOP:17Binding 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 memoryDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:1493
Increased Pro-inflammatory mediators
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.12KE:289
Decrease, Translocator protein (TSPO)
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.2KE:286
Altered, Transcription of genes by the androgen receptor
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.2KE:1269
Increase, COX-2 expression
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT Endorsed0.3KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:285
Reduction, Vitellogenin synthesis in liver
KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT Endorsed0.38KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:285
Reduction, Vitellogenin synthesis in liver
KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.25KE:149
Increase, Inflammation
KE:288
Activation of specific nuclear receptors, Transcriptional change
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.17KE:285
Reduction, Vitellogenin synthesis in liver
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.15KE:54
Up Regulation, CD36
KE:258
Activation, SCD-1
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.12KE:140
Decreased, HSD17B10 expression
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.14KE:1493
Increased Pro-inflammatory mediators
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.12KE:756
Hippocampal gene expression, Altered
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.1KE:381
Reduced levels of BDNF
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.19KE:462
Up Regulation, SCD-1
KE:463
Up Regulation, FAS
KE:54
Up Regulation, CD36
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.33KE:462
Up Regulation, SCD-1
KE:474
Down Regulation, HMGCS2
KE:54
Up Regulation, CD36
KE:472
Down Regulation, CPT1A
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.14KE:520
Decreased sperm quantity or quality in the adult, Decreased fertility
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.2KE:1214
Altered gene expression specific to CAR activation, Hepatocytes
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-0.17KE:777
Increase, Inflammation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-0.2KE:149
Increase, Inflammation
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-0.4KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:799
Increased, HIF-1 heterodimer
KE:285
Reduction, Vitellogenin synthesis in liver
KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-0.45KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:802
Increased, HIF-1 alpha transcription
KE:219
Reduction, Plasma 17beta-estradiol concentrations
KE:285
Reduction, Vitellogenin synthesis in liver
KE:799
Increased, HIF-1 heterodimer
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:850
Induction, CYP1A2/CYP1A5
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.11KE:756
Hippocampal gene expression, Altered
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.11KE:1493
Increased Pro-inflammatory mediators
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.14KE:948
reduced production, VEGF
AOP:151AhR activation leading to preeclampsiaCardiovascular System DiseaseUnder Development0.29KE:1892
increase, placental insufficiency
KE:948
reduced production, VEGF
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.14KE:1066
Promotion, SIX-1 postive basal-type progenitor cells
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.12KE:1497
Increased, recruitment of inflammatory cells
AOP:201Juvenile hormone receptor agonism leading to male offspring induction associated population declineUnclassified-0.17KE:1206
Induction, Doublesex1 gene
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:149
Increase, Inflammation
AOP:218Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activityUnclassified-0.17KE:1141
Decreased, Reproductive Success
AOP:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-0.17KE:1141
Decreased, Reproductive Success
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder Development0.2KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.2KE:1239
Altered, Gene Expression
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149
Increase, Inflammation
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder Development0.17KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1493
Increased Pro-inflammatory mediators
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1493
Increased Pro-inflammatory mediators
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderUnder Development0.2KE:756
Hippocampal gene expression, Altered
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.2KE:286
Altered, Transcription of genes by the androgen receptor
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.25KE:286
Altered, Transcription of genes by the androgen receptor
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.25KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:285
Reduction, Vitellogenin synthesis in liver
KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.25KE: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 Development0.17KE:286
Altered, Transcription of genes by the androgen receptor
AOP:346Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiationUnclassifiedWPHA/WNT Endorsed0.2KE:1789
Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine System Disease; Reproductive System Disease; Cancer-0.2KE:286
Altered, Transcription of genes by the androgen receptor
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.12KE:1497
Increased, recruitment of inflammatory cells
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.09KE:1493
Increased Pro-inflammatory mediators
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.11KE:149
Increase, Inflammation
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.33KE:2020
Decrease, sox9 expression
KE:2021
Increase, slincR expression
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.33KE:2020
Decrease, sox9 expression
KE:2021
Increase, slincR expression
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:756
Hippocampal gene expression, Altered
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:756
Hippocampal gene expression, Altered
KE:850
Induction, CYP1A2/CYP1A5
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.11KE:2040
Decrease, GLI1/2 target gene expression
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.09KE:149
Increase, Inflammation
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular System DiseaseUnder Review0.12KE:1493
Increased Pro-inflammatory mediators
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.11KE:149
Increase, Inflammation
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.1KE:1497
Increased, recruitment of inflammatory cells
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.11KE:286
Altered, Transcription of genes by the androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-0.2KE:286
Altered, Transcription of genes by the androgen receptor
KE:219
Reduction, Plasma 17beta-estradiol concentrations
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:54
Up Regulation, CD36
AOP:529Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.12KE:2224
Dysregulation of transcriptional expression within PPAR signaling network
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.17KE:1239
Altered, Gene Expression
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:307
Increase, Vitellogenin synthesis in liver
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:307
Increase, Vitellogenin synthesis in liver
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:3
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:285
Reduction, Vitellogenin synthesis in liver
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.08KE:1493
Increased Pro-inflammatory mediators
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous System Disease-0.17KE:149
Increase, Inflammation
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:219
Reduction, Plasma 17beta-estradiol concentrations

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:148EGFR Activation Leading to Decreased Lung FunctionRespiratory System DiseaseUnder Development0.5KE:1250
Decrease, Lung function
KE:962
Increase, Mucin production
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226
Increased Respiratory irritability and Chronic Cough,
AOP:2035-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population declineReproductive System Disease-0.12KE:1141
Decreased, Reproductive Success
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.14KE:1556
Increase, lung cancer
AOP:302Lung surfactant function inhibition leading to decreased lung functionRespiratory System DiseaseUnder Development0.2KE:1250
Decrease, Lung function
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.29KE:1497
Increased, recruitment of inflammatory cells
KE:1670
Lung cancer
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.2KE:1757
Reduce, Sperm count
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.4KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1868
Hyperinflammation
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.25KE:1250
Decrease, Lung function
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1670
Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1670
Lung cancer
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.2KE:1250
Decrease, Lung function
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.25KE:1250
Decrease, Lung function
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:1670
Lung cancer
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory System Disease-0.17KE:1250
Decrease, Lung function
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory System Disease-0.17KE:1250
Decrease, Lung function
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.22KE:1497
Increased, recruitment of inflammatory cells
KE:1670
Lung cancer
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.25KE:1868
Hyperinflammation
KE:1497
Increased, recruitment of inflammatory cells
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-0.4KE:149
Increase, Inflammation
KE: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:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:486
systemic inflammation leading to hepatic steatosis
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.12KE:1284
Up Regulation, SREBF2
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.2KE:149
Increase, Inflammation
KE:1250
Decrease, Lung function
KE:1497
Increased, recruitment of inflammatory cells
KE:1239
Altered, Gene Expression
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.17KE:2040
Decrease, GLI1/2 target gene expression

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
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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.