Titanium dioxide

Titanium dioxide



Associated High Confidence AOPs
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Associated AOPs with Level of Relevance 1
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:155Inadequate DNA repair
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.2KE:317Altered, Cardiovascular development/function
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT Endorsed0.1KE:274Reduction, Testosterone synthesis by ovarian theca cells
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.25KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory System DiseaseUnder Development0.2KE:272Activation/Proliferation, T-cells
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.2KE:272Activation/Proliferation, T-cells
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.6KE:854Alterations, Cellular proliferation / hyperplasia
KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:69Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig CellReproductive System Disease-0.2KE:645Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells
AOP:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-0.12KE:664Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:104Altered ion channel activity leading impaired heart functionUnclassified-0.25KE:699Increased, cardiac arrthymia
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.17KE:710Increase, 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 Review0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory System Disease-0.2KE:734Increase, 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:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-0.33KE:777Increase, Inflammation (corneal cells)
KE:778Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-0.4KE:149Increase, Inflammation
KE:781Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.25KE:710Increase, 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:716Increase, 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:739Increase, 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:795Increase, 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:870Increase, Cell Proliferation
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular System DiseaseUnder Development0.2KE:937KE7 : Impaired, Vasodilation
KE:933KE6 : Depletion, Nitric Oxide
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.14KE:317Altered, Cardiovascular development/function
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive System Disease-0.17KE:1042Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.14KE:1067Proliferation/Clonal Expansion, aberrant basal cells
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive System Disease-0.38KE:1281Increased, DNA Damage-Repair
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.17KE:1262Apoptosis
AOP:213Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)Gastrointestinal System Disease; Inherited Metabolic Disorder-0.17KE:1115Increase, Reactive oxygen species
AOP:228NSAID induced PTGS2 inactivation to gastric ulcerGastrointestinal System Disease-0.2KE:1411Increased, leukocyte activation
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-0.09KE:40Decrease, Mitochondrial ATP production
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:870Increase, Cell Proliferation
KE:155Inadequate DNA repair
AOP:277Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody ResponseImmune System DiseaseWPHA/WNT Endorsed0.25KE:202Inhibition, Nuclear factor kappa B (NF-kB)
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:202Inhibition, Nuclear factor kappa B (NF-kB)
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149Increase, Inflammation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.5KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-0.5KE:1771Decrease, Adenosine triphosphate pool
KE:1825Increase, Cell death
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.5KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-0.5KE:1771Decrease, Adenosine triphosphate pool
KE:1825Increase, Cell death
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.11KE:1182Increase, 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:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.2KE:155Inadequate DNA repair
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.18KE:592Reduced, survival
KE:10042Abnormal development
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary System Disease-0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:348Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectoryUnclassifiedUnder Development0.2KE:406decreased, Fertility
AOP:349Inhibition of 11β-hydroxylase leading to decresed population trajectoryUnclassifiedUnder Development0.12KE:406decreased, Fertility
AOP:362Immune mediated hepatitisGastrointestinal System Disease; Immune System Disease-0.12KE:1817Apoptotic cell death
AOP:368Cytochrome oxidase inhibition leading to increased nasal lesionsUnclassified-0.33KE:1825Increase, Cell death
AOP:383Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosisGastrointestinal System DiseaseUnder Development0.17KE:1115Increase, Reactive oxygen species
AOP:386Deposition of ionizing energy leading to population decline via inhibition of photosynthesisReproductive System Disease-0.12KE:1115Increase, Reactive oxygen species
AOP:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive System Disease-0.25KE:40Decrease, Mitochondrial ATP production
KE:1115Increase, Reactive oxygen species
AOP:388Deposition of ionising energy leading to population decline via programmed cell deathReproductive System Disease-0.2KE:1864Increase, Programmed cell death
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.12KE:1821Decrease, Cell proliferation
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1869Diminished protective oxidative stress response
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-0.1KE:1825Increase, Cell death
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.33KE:1115Increase, Reactive oxygen species
KE:1607Increase, Necrosis
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1115Increase, Reactive oxygen species
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:870Increase, Cell Proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.18KE:870Increase, Cell Proliferation
KE:155Inadequate DNA repair
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.22KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:441Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiationCongenital Nervous System Abnormality; Nervous System Disease-0.14KE:1262Apoptosis
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.3KE:1554Increase Chromosomal Aberrations
KE:155Inadequate DNA repair
KE:1172Increased activation, Nuclear factor kappa B (NF-kB)
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1365Increase, Apoptosis
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.33KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
KE:870Increase, Cell Proliferation
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.09KE:1262Apoptosis
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.17KE:317Altered, Cardiovascular development/function
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.22KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous System Disease-0.05KE:1825Increase, Cell death
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:2050Increase, developmental abnormalities
AOP:467Knickkopf leading to mortalityUnclassified-0.11KE:2050Increase, developmental abnormalities
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.25KE:1497Increased, recruitment of inflammatory cells
KE:1825Increase, Cell death
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.2KE:870Increase, Cell Proliferation
KE:155Inadequate DNA repair
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular System Disease; Thoracic DiseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal System DiseaseUnder Review0.14KE:1825Increase, Cell death
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.2KE:1497Increased, recruitment of inflammatory cells
KE:2119Insulin resistance, increased
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.22KE:854Alterations, Cellular proliferation / hyperplasia
KE:1183Decreased, Apoptosis (Epithelial Cells)
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-0.29KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive System Disease; CancerUnder Review0.17KE:1896Genomic instability
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular System Disease-0.14KE:1365Increase, Apoptosis
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:524Gluten-driven immune activation leading to celiac disease in genetically predisposed individualsImmune System Disease; Gastrointestinal System Disease-0.11KE:2255Innate immune response, activation
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.11KE:1262Apoptosis
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous System Disease-0.17KE:149Increase, Inflammation
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.17KE:1262Apoptosis
AOP:564DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.Unclassified-0.09KE:40Decrease, Mitochondrial ATP production
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental Disorder Of Mental Health-0.17KE:1115Increase, Reactive oxygen species
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory System Disease-0.33KE:1825Increase, Cell death
AOP:574Inhibition, cytochrome oxidase leads to Loss of olfactory functionUnclassified-0.33KE:1825Increase, Cell death

Associated AOPs with Level of Relevance 2
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:6Antagonist binding to PPARα leading to body-weight lossSymptomWPHA/WNT Endorsed0.12KE:864Decreased, Body Weight
AOP:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive System Disease; Endocrine System Disease; Reproductive System DiseaseUnder Review0.2KE:406decreased, Fertility
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.25KE:406decreased, Fertility
KE:413Reduction, Testosterone synthesis in Leydig cells
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.2KE:337N/A, Impairment of reproductive capacity
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.43KE:406decreased, Fertility
KE:413Reduction, Testosterone synthesis in Leydig cells
KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:91Sodium channel inhibition leading to reduced survivalUnclassified-0.17KE:592Reduced, survival
AOP:95Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survivalUnclassified-0.17KE:592Reduced, survival
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-0.14KE:636Decreased, survival
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive System Disease-0.17KE:330Decrease, Fertility
AOP:139Alkylation of DNA leading to cancer 1Cancer-0.5KE:885Increase, Cancer
KE:155Inadequate DNA repair
AOP:148EGFR Activation Leading to Decreased Lung FunctionRespiratory System DiseaseUnder Development0.25KE:1250Decrease, Lung function
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.25KE:1497Increased, recruitment of inflammatory cells
KE:1458Pulmonary fibrosis
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226Increased Respiratory irritability and Chronic Cough,
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263Necrosis
KE:1262Apoptosis
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.33KE:149Increase, Inflammation
KE:1276Lung fibrosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.6KE:1393Hepatocytotoxicity
KE:1394Induction, persistent proliferation/sustained proliferation
KE:1395Liver Cancer
AOP:241Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System Disease-0.17KE:1458Pulmonary fibrosis
AOP:242Inhibition of lysyl oxidase leading to enhanced chronic fish toxicityUnclassified-0.12KE:636Decreased, survival
AOP:302Lung surfactant function inhibition leading to decreased lung functionRespiratory System DiseaseUnder Development0.2KE:1250Decrease, Lung function
AOP:313Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin diseaseImmune System Disease; Integumentary System Disease; Musculoskeletal System DiseaseUnder Development0.2KE:1709Psoriatic skin disease
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.6KE:1757Reduce, Sperm count
KE:155Inadequate DNA repair
KE:1365Increase, Apoptosis
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine System Disease; Reproductive System Disease; Reproductive System DiseaseUnder Development0.17KE:406decreased, Fertility
AOP:347Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System Disease-0.11KE:1458Pulmonary fibrosis
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular System DiseaseUnder Development0.29KE:1869Diminished protective oxidative stress response
KE:1846Thrombosis and Disseminated Intravascular Coagulation
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.5KE:1115Increase, Reactive oxygen species
KE:1276Lung fibrosis
KE:1172Increased activation, Nuclear factor kappa B (NF-kB)
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary System Disease-0.33KE:1115Increase, Reactive oxygen species
KE:1603Chronic kidney disease
AOP:398Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogoniaReproductive System DiseaseUnder Development0.17KE:406decreased, Fertility
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.25KE:1250Decrease, Lung function
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.4KE:1276Lung fibrosis
KE:1920Altered gene expression, TGF-β dependent fibrosis pathway
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:1276Lung fibrosis
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.6KE:1115Increase, Reactive oxygen species
KE:1250Decrease, Lung function
KE:1825Increase, Cell death
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.5KE:1250Decrease, Lung function
KE:1262Apoptosis
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory System Disease-0.17KE:1250Decrease, Lung function
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory System Disease-0.17KE:1250Decrease, Lung function
AOP:431Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Inherited Metabolic Disorder-0.4KE:1953Gestational diabetes mellitus
KE:1952Abnormal, Glucose homeostasis
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.17KE:2119Insulin resistance, increased
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder Development0.2KE:885Increase, Cancer
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive System Disease-0.4KE:406decreased, Fertility
KE:1115Increase, Reactive oxygen species
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-0.38KE:1115Increase, Reactive oxygen species
KE:2145Metabolic syndrome
KE:2119Insulin resistance, increased
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous System Disease-0.25KE:2150Neurological disorder
AOP:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.25KE:2150Neurological disorder
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.5KE:1115Increase, Reactive oxygen species
KE:885Increase, Cancer
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-0.2KE:885Increase, Cancer
AOP:551Increased Muscarinic M2 Receptor leading to ArrhythmiaSymptom-0.2KE:1106Occurrence, cardiac arrhythmia
AOP:554β-adrenergic receptor agonists leading to arrhythmias.Symptom-0.25KE:1106Occurrence, cardiac arrhythmia
AOP:559Inhibition of acetylcholinesterase (AChE) leading to arrhythmiasSymptom-0.2KE:1106Occurrence, cardiac arrhythmia
AOP:560Inhibition of Funny current (If) leading to ArrhythmiasSymptom-0.25KE:1106Occurrence, cardiac arrhythmia
AOP:562HCN Channel Inhibition leading to ArrhythmiasSymptom-0.2KE:1106Occurrence, cardiac arrhythmia

Associated AOPs with Level of Relevance 3
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:486systemic inflammation leading to hepatic steatosis
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.5KE:786Increase, Cytotoxicity (hepatocytes)
KE:787Increase, Regenerative cell proliferation (hepatocytes)
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.25KE:1287Glutathione synthesis
KE:1286Down Regulation, GSS and GSTs gene
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed0.75KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.5KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.33KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.4KE:1821Decrease, Cell proliferation
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder Review0.25KE:1115Increase, Reactive oxygen species
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal System DiseaseUnder Review0.33KE:1115Increase, Reactive oxygen species
KE:1753Chronic reactive oxygen species
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.57KE:1115Increase, Reactive oxygen species
KE:870Increase, Cell Proliferation
KE:1497Increased, recruitment of inflammatory cells
KE:1668Frustrated phagocytosis
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-0.25KE:1115Increase, Reactive oxygen species
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-0.25KE:1115Increase, Reactive oxygen species
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-0.25KE:1115Increase, Reactive oxygen species
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-0.2KE:1115Increase, Reactive oxygen species
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-0.4KE:1115Increase, Reactive oxygen species
KE:1771Decrease, Adenosine triphosphate pool
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-0.4KE:1115Increase, Reactive oxygen species
KE:1771Decrease, Adenosine triphosphate pool
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-0.4KE:1115Increase, Reactive oxygen species
KE:1365Increase, Apoptosis
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.33KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.4KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.8KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.4KE:1867Bradykinin system, hyperactivated
KE:1497Increased, recruitment of inflammatory cells
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.62KE:870Increase, Cell Proliferation
KE:1668Frustrated phagocytosis
KE:1115Increase, Reactive oxygen species
KE:1896Genomic instability
KE:1497Increased, recruitment of inflammatory cells
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular System Disease-0.17KE:1115Increase, Reactive oxygen species
KE:1919Increased, Cardiac Dysregulation
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.4KE:1262Apoptosis
KE:1458Pulmonary fibrosis
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1250Decrease, Lung function
KE:1993Increase, Pneumonia
KE:1497Increased, recruitment of inflammatory cells
KE:1198Activation, Macrophages
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.17KE:202Inhibition, Nuclear factor kappa B (NF-kB)
KE:1365Increase, Apoptosis
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.12KE:1115Increase, Reactive oxygen species
KE:1198Activation, Macrophages
AOP:453Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general populationGastrointestinal System Disease-0.15KE:1115Increase, Reactive oxygen species
KE:1198Activation, Macrophages
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.27KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal System Disease-0.15KE:1115Increase, Reactive oxygen species
KE:1198Activation, Macrophages
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.33KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1825Increase, Cell death
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.29KE:1115Increase, Reactive oxygen species
KE:1869Diminished protective oxidative stress response
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.06KE:1115Increase, Reactive oxygen species
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.15KE:1115Increase, Reactive oxygen species
KE:1198Activation, Macrophages

Associated AOPs with Level of Relevance 5
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.33KE:1115Increase, Reactive oxygen species
KE:1817Apoptotic cell death
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.6KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:885Increase, Cancer
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.4KE:1115Increase, Reactive oxygen species
KE:885Increase, Cancer
DISCLAIMER

TICToK is a database of tattoo ink chemicals compiled from different regulatory resources. The authors are not liable for any inaccuracies or omissions of any chemicals 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.