Copper

Copper



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

Associated AOPs with Level of Relevance 1
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-0.1KE:993Decrease, Abdominal muscle contraction
AOP:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive System Disease; Endocrine System Disease; Reproductive System DiseaseUnder Review0.2KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE:155Inadequate DNA repair
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.12KE:413Reduction, Testosterone synthesis in Leydig cells
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 Endorsed0.2KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:274Reduction, Testosterone synthesis by ovarian theca cells
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT Endorsed0.12KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa 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: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:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.06KE:454Increased, Triglyceride formation
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:454Increased, Triglyceride formation
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.29KE:413Reduction, Testosterone synthesis in Leydig cells
KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
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:77Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1Unclassified-0.14KE:341Impairment, Learning and memory
AOP:78Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1Unclassified-0.12KE:341Impairment, Learning and memory
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:87Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failureUnclassified-0.12KE:341Impairment, Learning and memory
AOP:88Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within casteUnclassified-0.14KE:341Impairment, Learning and memory
AOP:89Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failureUnclassified-0.12KE:341Impairment, Learning and memory
AOP:90Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2Unclassified-0.12KE:341Impairment, Learning and memory
AOP:96Axonal sodium channel modulation leading to acute mortalityUnclassified-0.17KE:602Increased, Ataxia, paralysis, or hyperactivity
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-0.14KE:341Impairment, Learning and memory
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: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-0.29KE:277Thyroid hormone synthesis, Decreased
KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:113Glutamate-gated chloride channel activation leading to acute mortalityUnclassified-0.17KE:764N/A, Ataxia, paralysis, or hyperactivity
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:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.29KE:277Thyroid hormone synthesis, Decreased
KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-0.1KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-0.09KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.29KE:768Increase, Cytotoxicity
KE:870Increase, Cell Proliferation
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.11KE:1493Increased Pro-inflammatory mediators
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular System DiseaseUnder Development0.2KE:927KE1 : S-Glutathionylation, eNOS
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:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.12KE:277Thyroid hormone synthesis, Decreased
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:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System DiseaseWPHA/WNT Endorsed0.12KE:1497Increased, recruitment of inflammatory cells
AOP:175Thyroperoxidase inhibition leading to altered amphibian metamorphosisUnclassified-0.25KE:277Thyroid hormone synthesis, Decreased
AOP:176Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosisUnclassified-0.2KE:277Thyroid hormone synthesis, Decreased
AOP:188Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosisUnclassified-0.2KE:277Thyroid hormone synthesis, Decreased
AOP:192Pendrin inhibition leading to altered amphibian metamorphosisUnclassified-0.25KE:277Thyroid hormone synthesis, Decreased
AOP:193Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosisUnclassified-0.25KE:277Thyroid hormone synthesis, Decreased
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:149Increase, Inflammation
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 Endorsed0.5KE:1262Apoptosis
KE:1503Histone acetylation, increase
KE:1505Cell cycle, disrupted
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:218Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activityUnclassified-0.17KE:1141Decreased, Reproductive Success
AOP:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-0.17KE:1141Decreased, Reproductive Success
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-0.09KE:40Decrease, Mitochondrial ATP production
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder Development0.2KE:277Thyroid hormone synthesis, Decreased
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.29KE:870Increase, Cell Proliferation
KE:155Inadequate DNA repair
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.2KE:1503Histone acetylation, increase
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-0.25KE:1771Decrease, Adenosine triphosphate pool
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-0.25KE:1771Decrease, Adenosine triphosphate pool
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:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.08KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:315Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody ResponseImmune System DiseaseUnder Development0.4KE:1717Suppression of STAT5 binding to cytokine gene promoters
KE:1716Blockade of STAT5 phosphorylation
AOP:320Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortalityUnclassifiedUnder Development0.11KE:1750Increased inflammatory immune responses
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.18KE:10041Altered metabolic rate
KE:10042Abnormal development
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.2KE:155Inadequate DNA repair
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary System Disease-0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:346Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiationUnclassifiedWPHA/WNT Endorsed0.4KE:1789Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
KE:1790Increased, Differentiation to Testis
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder Review0.12KE:277Thyroid hormone synthesis, Decreased
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:277Thyroid hormone synthesis, Decreased
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:277Thyroid hormone synthesis, Decreased
AOP:374Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitisNervous System DiseaseUnder Development0.25KE:352N/A, Neurodegeneration
AOP:376Androgen receptor agonism leading to male-biased sex ratioUnclassifiedWPHA/WNT Endorsed0.25KE:1790Increased, Differentiation to Testis
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.17KE:1115Increase, Reactive oxygen species
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: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:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-0.1KE:1008Reduced, Hearing
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.5KE:1115Increase, Reactive oxygen species
KE:1607Increase, Necrosis
KE:759Increased, Kidney Failure
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1115Increase, Reactive oxygen species
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.2KE:1115Increase, Reactive oxygen species
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.25KE:1262Apoptosis
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-0.27KE:870Increase, Cell Proliferation
KE:1493Increased Pro-inflammatory mediators
KE:155Inadequate DNA repair
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.44KE:149Increase, Inflammation
KE:1971Increased, tumor growth
KE:1262Apoptosis
KE:1241Increased, Motility
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 Development0.1KE:155Inadequate DNA repair
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.14KE:352N/A, Neurodegeneration
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-0.18KE:2011Emphysema
KE: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:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:2050Increase, developmental abnormalities
AOP:467Knickkopf leading to mortalityUnclassified-0.11KE:2050Increase, developmental abnormalities
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular System DiseaseUnder Review0.12KE:1493Increased Pro-inflammatory mediators
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular System Disease; Thoracic DiseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
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-0.3KE:1497Increased, recruitment of inflammatory cells
KE:2125Increased fat mass
KE:2119Insulin resistance, increased
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:539Decreased Sodium/Potassium ATPase activity leads to Heart failureCardiovascular System Disease-0.14KE:2261Decreased, blood plasma volume
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-0.33KE:1115Increase, Reactive oxygen species
KE:2195Increase, CNS Neural 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 Endorsed0.25KE:863Increased, Catabolism of Muscle Protein
KE:864Decreased, Body Weight
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 Endorsed0.25KE:341Impairment, Learning and memory
KE:352N/A, Neurodegeneration
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:341Impairment, Learning and memory
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 Endorsed0.2KE:1493Increased Pro-inflammatory mediators
KE:341Impairment, Learning and memory
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.08KE:345N/A, Liver Steatosis
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal System DiseaseUnder Development0.4KE:719Increase, hepatocellular adenomas and carcinomas
KE:716Increase, cell proliferation (hepatocytes)
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.25KE:277Thyroid hormone synthesis, Decreased
KE:402Cognitive function, decreased
AOP:43Disruption of VEGFR Signaling Leading to Developmental DefectsUnclassifiedWPHA/WNT Endorsed0.4KE:28Reduction, Angiogenesis
KE:1001Increased, Developmental Defects
AOP:48Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.Developmental Disorder Of Mental HealthWPHA/WNT Endorsed0.22KE:341Impairment, Learning and memory
KE:352N/A, Neurodegeneration
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.2KE:277Thyroid hormone synthesis, Decreased
KE:341Impairment, Learning and memory
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal System DiseaseUnder Review0.4KE:719Increase, hepatocellular adenomas and carcinomas
KE:716Increase, cell proliferation (hepatocytes)
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.33KE:768Increase, Cytotoxicity
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System DiseaseUnder Development0.5KE:719Increase, hepatocellular adenomas and carcinomas
KE:716Increase, cell proliferation (hepatocytes)
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:277Thyroid hormone synthesis, Decreased
KE:402Cognitive function, decreased
AOP:139Alkylation of DNA leading to cancer 1Cancer-0.5KE:885Increase, Cancer
KE:155Inadequate DNA repair
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226Increased Respiratory irritability and Chronic Cough,
AOP:2035-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population declineReproductive System Disease-0.12KE:1141Decreased, Reproductive Success
AOP:205AOP from chemical insult to cell deathUnclassified-0.33KE:1263Necrosis
KE:1262Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.6KE:1393Hepatocytotoxicity
KE:1394Induction, persistent proliferation/sustained proliferation
KE:1395Liver Cancer
AOP:227NSAID induced PTGS1 inactivation to gastric ulcerGastrointestinal System Disease-0.14KE:1385Activated, gastric ulcer formation
AOP:228NSAID induced PTGS2 inactivation to gastric ulcerGastrointestinal System Disease-0.2KE:1385Activated, gastric ulcer formation
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous System Disease-0.14KE:1514Neurodegeneration
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:1549Liver Injury
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous System Disease-0.1KE:352N/A, Neurodegeneration
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.33KE:1493Increased Pro-inflammatory mediators
KE:1193N/A, Breast Cancer
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic Disease; Thoracic Disease; CancerUnder Development0.33KE:1493Increased Pro-inflammatory mediators
KE:1193N/A, Breast Cancer
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderUnder Development0.2KE:402Cognitive function, decreased
AOP:304TBX1 inhibition leading to congenital cardiac conotruncal anomaliesCardiovascular System Disease-0.17KE:1685Anomalies, Congenital cardiac conotruncal
AOP:362Immune mediated hepatitisGastrointestinal System Disease; Immune System Disease-0.12KE:1820Immune mediated hepatitis
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: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:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.4KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
AOP:405Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive functionCognitive Disorder-0.2KE:402Cognitive function, decreased
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.33KE:1868Hyperinflammation
KE:1869Diminished protective oxidative stress response
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:433hERG channel blockade leading to sudden cardiac deathCardiovascular System Disease-0.17KE:1964Sudden cardiac death
AOP:442Binding to voltage gate sodium channels during development leads to cognitive impairmentCognitive DisorderUnder Review0.14KE:402Cognitive function, decreased
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.08KE:759Increased, Kidney Failure
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.33KE:277Thyroid hormone synthesis, Decreased
KE:2119Insulin resistance, increased
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.12KE:402Cognitive function, decreased
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:277Thyroid hormone synthesis, Decreased
KE:402Cognitive function, decreased
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.25KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder Development0.2KE:885Increase, Cancer
AOP:475Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neuronsDevelopmental Disorder Of Mental HealthUnder Development0.12KE:341Impairment, Learning and memory
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.3KE:870Increase, Cell Proliferation
KE:155Inadequate DNA repair
KE:2083Occurrence of Cataracts
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental Disorder Of Mental HealthUnder Review0.12KE:341Impairment, Learning and memory
AOP:485Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognitionCognitive Disorder-0.14KE:402Cognitive function, decreased
AOP:486Binding to the extracellular protein laminin leading to decreased cognitive functionCognitive Disorder-0.14KE:402Cognitive function, decreased
AOP:490Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanismsDevelopmental Disorder Of Mental Health-0.09KE:341Impairment, Learning and memory
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.33KE:854Alterations, Cellular proliferation / hyperplasia
KE:1183Decreased, Apoptosis (Epithelial Cells)
KE:2135Prostate cancer
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-0.75KE:2149Increased intracelluar Iron accumulation
KE:191Neuronal dysfunction
KE:2150Neurological disorder
AOP:499Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter releaseDevelopmental Disorder Of Mental Health-0.25KE:341Impairment, Learning and memory
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-0.57KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
KE:341Impairment, Learning and memory
KE:352N/A, Neurodegeneration
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular System Disease-0.17KE:2161Increase, Vascular disrupting effects
AOP:508Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathwayCardiovascular System Disease-0.14KE:2161Increase, Vascular disrupting effects
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular System Disease-0.14KE:2161Increase, Vascular disrupting effects
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.1KE:2161Increase, Vascular disrupting effects
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.2KE:341Impairment, Learning and memory
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.15KE:2115Altered, cholesterol metabolism
KE:341Impairment, Learning and memory
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.17KE:341Impairment, Learning and memory
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:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.22KE:1262Apoptosis
KE:341Impairment, Learning and memory
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:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.29KE:1493Increased Pro-inflammatory mediators
KE:244Alkylation, Protein
AOP:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:486systemic inflammation leading to hepatic steatosis
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary System Disease-0.4KE:795Increase, Regenerative cell proliferation (urothelial cells)
KE:793Increase, Urinary bladder calculi
AOP:128Kidney dysfunction by decreased thyroid hormoneUrinary System DiseaseUnder Development0.09KE:277Thyroid hormone synthesis, Decreased
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.38KE:1287Glutathione synthesis
KE:1289Perturbation of cholesterol
KE:1286Down Regulation, GSS and GSTs gene
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.4KE:40Decrease, Mitochondrial ATP production
KE:244Alkylation, Protein
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-0.4KE:1115Increase, Reactive oxygen species
KE:1769Increase, Body fluid overload
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-0.2KE:1115Increase, Reactive oxygen species
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.5KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
KE:1505Cell cycle, disrupted
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.6KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
KE:1505Cell cycle, disrupted
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:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.17KE:1115Increase, Reactive oxygen species
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular System Disease-0.25KE:1115Increase, Reactive oxygen species
KE:1926Increased, Vascular fibrosis
KE:1919Increased, Cardiac Dysregulation
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.25KE:1262Apoptosis
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
KE:1198Activation, Macrophages
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.18KE:1115Increase, Reactive oxygen species
KE:2001Cardiac hypertrophy
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: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:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive System Disease-0.4KE:1115Increase, Reactive oxygen species
KE:2131Conjugation, GSH
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.33KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.31KE:1115Increase, Reactive oxygen species
KE:1816Mitochondrial dysfunction EMPTY
KE:1493Increased Pro-inflammatory mediators
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:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal System Disease-0.75KE:719Increase, hepatocellular adenomas and carcinomas
KE:786Increase, Cytotoxicity (hepatocytes)
KE:787Increase, Regenerative cell proliferation (hepatocytes)
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.62KE:870Increase, Cell Proliferation
KE:1668Frustrated phagocytosis
KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
KE:1090Increased, mesotheliomas
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.36KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
KE:2034liver dysfunction
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.44KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1816Mitochondrial dysfunction EMPTY
KE:759Increased, Kidney Failure
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.43KE:1115Increase, Reactive oxygen species
KE:1869Diminished protective oxidative stress response
KE:402Cognitive function, decreased
AOP:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.5KE:2149Increased intracelluar Iron accumulation
KE:2150Neurological disorder
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:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.12KE:1115Increase, Reactive oxygen species
KE:2161Increase, Vascular disrupting effects
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.6KE:1115Increase, Reactive oxygen species
KE:1060Alteration, lipid metabolism
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.