Arsenic

Arsenic



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:3Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficitsNervous System DiseaseWPHA/WNT Endorsed0.43KE:177Mitochondrial dysfunction
KE:188Neuroinflammation
KE:887Inhibition, NADH-ubiquinone oxidoreductase (complex I)
AOP:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-0.3KE:1264Increase, Nuclear receptor E75b gene expression
KE:993Decrease, Abdominal muscle contraction
KE:1265Increase, Fushi tarazu factor-1 gene expression
AOP:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous System DiseaseUnder Development0.22KE:757Hippocampal anatomy, Altered
KE:756Hippocampal gene expression, Altered
AOP:10Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brainNervous System DiseaseWPHA/WNT Endorsed0.17KE:616Occurrence, A paroxysmal depolarizing shift
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 Review0.5KE:413Reduction, Testosterone synthesis in Leydig cells
KE:447Reduction, Cholesterol transport in mitochondria
KE:266Decrease, Steroidogenic acute regulatory protein (STAR)
KE:289Decrease, Translocator protein (TSPO)
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.4KE:317Altered, Cardiovascular development/function
KE:1269Increase, COX-2 expression
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT Endorsed0.4KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:274Reduction, Testosterone synthesis by ovarian theca cells
KE:285Reduction, Vitellogenin synthesis in liver
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT Endorsed0.38KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:285Reduction, Vitellogenin synthesis in liver
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.38KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:288Activation of specific nuclear receptors, Transcriptional change
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.17KE:285Reduction, Vitellogenin synthesis in liver
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.12KE:140Decreased, HSD17B10 expression
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.29KE:68Accumulation, Collagen
KE:1493Increased Pro-inflammatory mediators
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory System DiseaseUnder Development0.2KE: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-0.25KE:462Up Regulation, SCD-1
KE:454Increased, Triglyceride formation
KE:463Up Regulation, FAS
KE:54Up Regulation, CD36
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.42KE:454Increased, Triglyceride formation
KE:54Up Regulation, CD36
KE:462Up Regulation, SCD-1
KE:474Down Regulation, HMGCS2
KE:472Down Regulation, CPT1A
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:73Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundityUnclassified-0.15KE:10059Decreased LH surge for 24 hours
KE:531Decreased, LH Surge
AOP:77Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1Unclassified-0.29KE:177Mitochondrial dysfunction
KE: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-0.25KE:177Mitochondrial dysfunction
KE:341Impairment, Learning and memory
AOP:79Nicotinic acetylcholine receptor activation contributes to impaired hive thermoregulation and leads to colony loss/failureUnclassified-0.2KE:177Mitochondrial dysfunction
AOP:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-0.25KE:177Mitochondrial dysfunction
KE:664Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:87Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failureUnclassified-0.25KE:177Mitochondrial dysfunction
KE: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:94Sodium channel inhibition leading to congenital malformationsUnclassified-0.17KE:445Respiratory distress/arrest
AOP:102Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transitionReproductive System Disease-0.1KE:690Reduced, Luteinizing hormone (LH), plasma
AOP:103Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpointReproductive System Disease-0.1KE:690Reduced, Luteinizing hormone (LH), plasma
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:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.33KE:747Decreased, Prolactin
KE:749Decreased, Progesterone from corpus luteum
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: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:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-0.4KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:799Increased, HIF-1 heterodimer
KE:285Reduction, Vitellogenin synthesis in liver
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-0.45KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:802Increased, HIF-1 alpha transcription
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:285Reduction, Vitellogenin synthesis in liver
KE:799Increased, HIF-1 heterodimer
AOP:126Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulationUnclassified-0.15KE:10059Decreased LH surge for 24 hours
KE:531Decreased, LH Surge
AOP:130Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicityGastrointestinal System DiseaseUnder Development0.09KE:177Mitochondrial dysfunction
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.17KE:850Induction, CYP1A2/CYP1A5
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 Review0.33KE:68Accumulation, Collagen
KE:1493Increased Pro-inflammatory mediators
KE:177Mitochondrial dysfunction
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.29KE:317Altered, Cardiovascular development/function
KE:948reduced production, VEGF
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive System Disease-0.33KE:1043Hypertrophy/hyperplasia, smooth muscle
KE:1042Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive System Disease; Cancer-0.29KE:1066Promotion, SIX-1 postive basal-type progenitor cells
KE: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 Endorsed0.25KE:68Accumulation, Collagen
KE:1497Increased, recruitment of inflammatory cells
AOP:201Juvenile hormone receptor agonism leading to male offspring induction associated population declineUnclassified-0.17KE:1206Induction, Doublesex1 gene
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-0.5KE:1115Increase, Reactive oxygen species
KE:177Mitochondrial dysfunction
KE:1262Apoptosis
KE:1281Increased, DNA Damage-Repair
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive System DiseaseWPHA/WNT Endorsed0.33KE:1262Apoptosis
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:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-0.17KE:1390Sexual behavior, decreased
AOP:241Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosisMusculoskeletal System Disease; Respiratory System Disease-0.17KE:68Accumulation, Collagen
AOP:256Inhibition of mitochondrial DNA polymerase gamma leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:177Mitochondrial dysfunction
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.4KE:40Decrease, Mitochondrial ATP production
KE:177Mitochondrial dysfunction
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder Development0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:276Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndromeUrinary System Disease-0.17KE:887Inhibition, NADH-ubiquinone oxidoreductase (complex I)
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149Increase, Inflammation
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder Development0.17KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.2KE:286Altered, Transcription of genes by the androgen receptor
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.25KE:286Altered, Transcription of genes by the androgen receptor
AOP:309Luteinizing hormone receptor antagonism leading to reproductive dysfunctionUnclassified-0.29KE:1693Reduction, Plasma progesterone concentration
KE:1692Reduction, Progesterone synthesis
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.25KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:285Reduction, Vitellogenin synthesis in liver
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:318Glucocorticoid Receptor activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:291Accumulation, Triglyceride
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.18KE:592Reduced, survival
KE:10042Abnormal development
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-0.17KE:807Decreased, cholesterol
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.25KE:286Altered, 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:286Altered, Transcription of genes by the androgen receptor
AOP:346Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiationUnclassifiedWPHA/WNT Endorsed0.2KE:1789Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:362Immune mediated hepatitisGastrointestinal System Disease; Immune System Disease-0.12KE:177Mitochondrial dysfunction
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine System Disease; Reproductive System Disease; Cancer-0.2KE:286Altered, Transcription of genes by the androgen receptor
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 Development0.5KE:188Neuroinflammation
KE:352N/A, Neurodegeneration
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal System Disease; Respiratory System DiseaseUnder Development0.33KE:1115Increase, Reactive oxygen species
KE:68Accumulation, Collagen
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:394SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)Endocrine System DiseaseUnder Development0.14KE:1847Increased SARS-CoV-2 production
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:428Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosisGastrointestinal System DiseaseUnder Development0.33KE:1854Dysregulation, ACE2 expression and activity
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:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary System DiseaseUnder Development0.4KE:177Mitochondrial dysfunction
KE:1392Oxidative Stress
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:440Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasiaBenign Neoplasm; Endocrine System Disease; Reproductive System Disease; Reproductive System Disease; Cancer; Endocrine System DiseaseUnder Development0.11KE:1052Hyperplasia, ovarian epithelium
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 Development0.2KE:1554Increase Chromosomal Aberrations
KE:155Inadequate DNA repair
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1392Oxidative Stress
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.33KE:2020Decrease, sox9 expression
KE:2021Increase, slincR expression
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.5KE:2020Decrease, sox9 expression
KE:317Altered, Cardiovascular development/function
KE:2021Increase, slincR expression
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
KE:2040Decrease, GLI1/2 target gene expression
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous System Disease-0.11KE:177Mitochondrial dysfunction
KE:1392Oxidative Stress
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 Review0.25KE:1493Increased Pro-inflammatory mediators
KE:1392Oxidative Stress
AOP:478Deposition of energy leading to occurrence of cataractsNervous System Disease; Monogenic DiseaseUnder Review0.4KE:870Increase, Cell Proliferation
KE:1636Increase, Chromosomal aberrations
KE:155Inadequate DNA repair
KE:1392Oxidative Stress
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular System Disease; Thoracic DiseaseUnder Development0.43KE:177Mitochondrial dysfunction
KE:1532Decrease, Cardiac contractility
KE:1392Oxidative Stress
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular System Disease; Thoracic DiseaseUnder Development0.6KE:40Decrease, Mitochondrial ATP production
KE:177Mitochondrial dysfunction
KE:1532Decrease, Cardiac contractility
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal System DiseaseUnder Review0.14KE:1392Oxidative Stress
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive System Disease-0.4KE:1115Increase, Reactive oxygen species
KE:1445Increase, Lipid peroxidation
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:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-0.2KE:286Altered, Transcription of genes by the androgen receptor
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-0.33KE:2251Estradiol availability, increased
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular System Disease-0.17KE:1392Oxidative Stress
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular System Disease-0.29KE:177Mitochondrial dysfunction
KE:1392Oxidative Stress
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.1KE:1392Oxidative Stress
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.4KE:291Accumulation, Triglyceride
KE:54Up Regulation, CD36
AOP:518Liver X Receptor (LXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:291Accumulation, Triglyceride
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.43KE:1115Increase, Reactive oxygen species
KE:1445Increase, Lipid peroxidation
KE:1392Oxidative Stress
AOP:524Gluten-driven immune activation leading to celiac disease in genetically predisposed individualsImmune System Disease; Gastrointestinal System Disease-0.11KE:1931Intestinal barrier, disruption
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-0.25KE:291Accumulation, Triglyceride
KE:2224Dysregulation of transcriptional expression within PPAR signaling network
AOP:531VEGFR inhibition leading to Keratinocyte differentiation-associate Hand-foot skin reactionUnclassified-0.12KE:11005Hyperkeratosis
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:307Increase, Vitellogenin synthesis in liver
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous System Disease-0.17KE:149Increase, Inflammation
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-0.4KE:2251Estradiol availability, increased
KE:2294Plasma estradiol, increased
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.17KE:1262Apoptosis

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: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 Endorsed0.5KE:188Neuroinflammation
KE:341Impairment, Learning and memory
KE:352N/A, Neurodegeneration
KE:381Reduced 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 Endorsed0.2KE:341Impairment, Learning and memory
KE:381Reduced levels of BDNF
AOP:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.29KE:445Respiratory distress/arrest
KE:351Increased Mortality
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 Endorsed0.4KE:1493Increased Pro-inflammatory mediators
KE:188Neuroinflammation
KE:341Impairment, Learning and memory
KE:1392Oxidative Stress
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.4KE:286Altered, Transcription of genes by the androgen receptor
KE:337N/A, Impairment of reproductive capacity
AOP:28Cyclooxygenase inhibition leading reproductive failureReproductive System Disease-0.17KE:253N/A, Reproductive failure
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.38KE:345N/A, Liver Steatosis
KE:177Mitochondrial dysfunction
KE:291Accumulation, Triglyceride
KE:54Up Regulation, CD36
KE:258Activation, SCD-1
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:40Covalent Protein binding leading to Skin SensitisationIntegumentary System DiseaseWPHA/WNT Endorsed0.4KE:827sensitisation, skin
KE:272Activation/Proliferation, T-cells
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderWPHA/WNT Endorsed0.38KE:757Hippocampal anatomy, Altered
KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
AOP:43Disruption of VEGFR Signaling Leading to Developmental DefectsUnclassifiedWPHA/WNT Endorsed0.2KE: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 Endorsed0.44KE:177Mitochondrial dysfunction
KE:188Neuroinflammation
KE: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:341Impairment, Learning and memory
KE:381Reduced levels of BDNF
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:96Axonal sodium channel modulation leading to acute mortalityUnclassified-0.5KE:599prolonged, Depolarization of neuronal membrane
KE:602Increased, Ataxia, paralysis, or hyperactivity
KE:351Increased Mortality
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-0.29KE:636Decreased, survival
KE:341Impairment, Learning and memory
AOP:104Altered ion channel activity leading impaired heart functionUnclassified-0.5KE:699Increased, cardiac arrthymia
KE:351Increased Mortality
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.33KE:713Increase, Adenomas/carcinomas (renal tubular)
KE: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 Review0.6KE:719Increase, hepatocellular adenomas and carcinomas
KE:1214Altered gene expression specific to CAR activation, Hepatocytes
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-0.5KE:768Increase, Cytotoxicity
KE:719Increase, hepatocellular adenomas and carcinomas
KE:769Increase, Oxidative metabolism
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory System Disease-0.4KE:736Increase, Adenomas/carcinomas (bronchioloalveolar)
KE:734Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:113Glutamate-gated chloride channel activation leading to acute mortalityUnclassified-0.33KE:764N/A, Ataxia, paralysis, or hyperactivity
KE:351Increased Mortality
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.5KE:713Increase, Adenomas/carcinomas (renal tubular)
KE: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 Development0.5KE:719Increase, hepatocellular adenomas and carcinomas
KE:716Increase, cell proliferation (hepatocytes)
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive System Disease-0.33KE:330Decrease, Fertility
KE:807Decreased, cholesterol
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.33KE:757Hippocampal anatomy, Altered
KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
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 Development0.5KE:1250Decrease, Lung function
KE:962Increase, Mucin production
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular System DiseaseUnder Development0.3KE:937KE7 : Impaired, Vasodilation
KE:952Hypertension
KE:933KE6 : Depletion, Nitric Oxide
AOP:151AhR activation leading to preeclampsiaCardiovascular System DiseaseUnder Development0.29KE:1893increase, Preeclampsia
KE:948reduced production, VEGF
AOP:155Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.17KE:351Increased Mortality
AOP:156Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.17KE:351Increased Mortality
AOP:157Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.17KE:351Increased Mortality
AOP:158Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.17KE:351Increased Mortality
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT Endorsed0.12KE:351Increased Mortality
AOP:160Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortalityUnclassified-0.14KE:351Increased Mortality
AOP:161Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortalityUnclassified-0.14KE:351Increased Mortality
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.11KE:1226Increased Respiratory irritability and Chronic Cough,
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal System DiseaseWPHA/WNT Endorsed0.8KE:1393Hepatocytotoxicity
KE:1394Induction, persistent proliferation/sustained proliferation
KE:1395Liver Cancer
KE:1392Oxidative Stress
AOP:237Substance interaction with lung resident cell membrane components leading to atherosclerosisCardiovascular System DiseaseUnder Development0.2KE:1443Atherosclerosis
AOP:242Inhibition of lysyl oxidase leading to enhanced chronic fish toxicityUnclassified-0.12KE:636Decreased, survival
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-0.18KE:40Decrease, Mitochondrial ATP production
KE:1521Decrease, Growth
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous System Disease-0.29KE:1514Neurodegeneration
KE:1392Oxidative Stress
AOP:261L-type calcium channel blockade leading to heart failure via decrease in cardiac contractilityCardiovascular System DiseaseUnder Development0.25KE:1532Decrease, Cardiac contractility
KE:1535Heart failure
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development
AOP:270Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activityUnclassified-0.12KE:10016Impaired locomotor activity
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT Endorsed0.57KE:870Increase, Cell Proliferation
KE:1556Increase, lung cancer
KE:155Inadequate DNA repair
KE:1636Increase, Chromosomal aberrations
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural Tube Defect-0.4KE:1561Neural tube defects
KE:1239Altered, Gene Expression
AOP:279Microtubule interacting drugs lead to peripheral neuropathyNervous System Disease-0.25KE:1583Sensory axonal peripheral neuropathy
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous System Disease-0.1KE:352N/A, Neurodegeneration
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.5KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-0.25KE:1521Decrease, Growth
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.5KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-0.25KE:1521Decrease, Growth
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:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic Disease; Chromosomal DiseaseWPHA/WNT Endorsed0.4KE:155Inadequate DNA repair
KE:1636Increase, Chromosomal aberrations
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive DisorderUnder Development0.6KE:757Hippocampal anatomy, Altered
KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
AOP:302Lung surfactant function inhibition leading to decreased lung functionRespiratory System DiseaseUnder Development0.2KE:1250Decrease, Lung function
AOP:312Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​Unclassified-0.17KE:351Increased Mortality
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:320Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortalityUnclassifiedUnder Development0.33KE:1847Increased SARS-CoV-2 production
KE:1750Increased inflammatory immune responses
KE:351Increased Mortality
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.4KE:1757Reduce, Sperm count
KE:155Inadequate DNA repair
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder Review0.12KE:351Increased Mortality
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:351Increased Mortality
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:351Increased Mortality
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular System DiseaseUnder Development0.43KE:1847Increased SARS-CoV-2 production
KE: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:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.25KE:1821Decrease, Cell proliferation
KE:351Increased Mortality
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-0.5KE:1868Hyperinflammation
KE:1847Increased SARS-CoV-2 production
KE:1869Diminished protective oxidative stress response
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-0.1KE:351Increased Mortality
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.33KE:1115Increase, Reactive oxygen species
KE:1670Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1670Lung cancer
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-0.4KE:1115Increase, Reactive oxygen species
KE:1250Decrease, Lung function
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-0.5KE:1250Decrease, Lung function
KE:1262Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.5KE:870Increase, Cell Proliferation
KE:1670Lung cancer
AOP:422Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruptionGastrointestinal System DiseaseUnder Development0.4KE:1847Increased SARS-CoV-2 production
KE:1931Intestinal barrier, disruption
AOP:430Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferationViral Infectious DiseaseUnder Development0.4KE:1847Increased SARS-CoV-2 production
KE:1939Viral infection and host-to-host transmission, proliferated
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-0.33KE:1961Prolongation of Action Potential Duration
KE:1964Sudden cardiac death
AOP:442Binding to voltage gate sodium channels during development leads to cognitive impairmentCognitive DisorderUnder Review0.29KE:757Hippocampal anatomy, Altered
KE:402Cognitive function, decreased
AOP:449Ceramide synthase inhibition leading to neural tube defectsNeural Tube Defect-0.14KE:1561Neural tube defects
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.57KE:352N/A, Neurodegeneration
KE:1583Sensory axonal peripheral neuropathy
KE:351Increased Mortality
KE:1392Oxidative Stress
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.44KE:1115Increase, Reactive oxygen species
KE:870Increase, Cell Proliferation
KE:1497Increased, recruitment of inflammatory cells
KE:1670Lung cancer
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.27KE:2008Chronic obstructive pulmonary disease
KE:1262Apoptosis
KE:1392Oxidative Stress
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.33KE:2119Insulin resistance, increased
KE:1392Oxidative Stress
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.25KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.44KE:850Induction, CYP1A2/CYP1A5
KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
KE:1392Oxidative Stress
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.38KE:1868Hyperinflammation
KE:1847Increased SARS-CoV-2 production
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:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental Disorder Of Mental HealthUnder Review0.25KE:341Impairment, Learning and memory
KE:1392Oxidative Stress
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-0.27KE:2121decreased, Intellectual Quotient
KE:188Neuroinflammation
KE:341Impairment, Learning and memory
AOP:495Androgen receptor activation leading to prostate cancerReproductive System Disease; Cancer-0.44KE:286Altered, Transcription of genes by the androgen receptor
KE: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-0.62KE:2145Metabolic syndrome
KE:1392Oxidative Stress
KE:177Mitochondrial dysfunction
KE:1115Increase, Reactive oxygen species
KE:2119Insulin resistance, increased
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous System Disease-0.5KE:191Neuronal dysfunction
KE:2150Neurological disorder
AOP:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.5KE:2150Neurological disorder
KE:1392Oxidative Stress
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:530Endocytotic lysosomal uptake leads to intestinal barrier disruptionGastrointestinal System Disease-0.4KE:177Mitochondrial dysfunction
KE:1931Intestinal barrier, disruption
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.33KE:341Impairment, Learning and memory
KE:1239Altered, Gene Expression
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-0.67KE:1115Increase, Reactive oxygen species
KE:885Increase, Cancer
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1392Oxidative Stress
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental Disorder Of Mental Health-0.67KE:1262Apoptosis
KE:2233Decreased, ERαβ heterodimers
KE:1392Oxidative Stress
KE:188Neuroinflammation
KE:341Impairment, Learning and memory
KE:2151Disruption, neurotransmitter release
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.33KE:307Increase, Vitellogenin synthesis in liver
KE:351Increased Mortality
AOP:539Decreased Sodium/Potassium ATPase activity leads to Heart failureCardiovascular System Disease-0.29KE:2261Decreased, blood plasma volume
KE:1535Heart failure
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:552Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)Cardiovascular System Disease-0.17KE:1535Heart failure
AOP:553Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failureCardiovascular System Disease-0.5KE:1532Decrease, Cardiac contractility
KE:1535Heart failure
AOP:554β-adrenergic receptor agonists leading to arrhythmias.Symptom-0.25KE:1106Occurrence, cardiac arrhythmia
AOP:555Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failureCardiovascular System Disease-0.6KE:2283Increased the early premature depolarizations during repolarization
KE:1961Prolongation of Action Potential Duration
KE:1535Heart failure
AOP:556Decreased Na/K ATPase activity leading to heart failureCardiovascular System Disease-0.33KE:1532Decrease, Cardiac contractility
KE:1535Heart failure
AOP:558Phosphodiesterase inhibition leading to heart failureCardiovascular System Disease-0.33KE:1532Decrease, Cardiac contractility
KE:1535Heart failure
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
AOP:564DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.Unclassified-0.27KE:2151Disruption, neurotransmitter release
KE:351Increased Mortality
KE: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:2121decreased, Intellectual Quotient
AOP:572Imidacloprid-Induced BMP4 inhibition Leading to Neural Tube Closure DefectsNeural Tube Defect-0.2KE:1561Neural tube defects
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory System Disease-0.33KE:2316Increased, pulmonary edema

Associated AOPs with Level of Relevance 3
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive System Disease; Endocrine System Disease; Reproductive System DiseaseUnder Review0.6KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:408reduction in ovarian granulosa cells, Aromatase (Cyp19a1)
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:486systemic inflammation leading to hepatic steatosis
AOP:69Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig CellReproductive System Disease-0.4KE:645Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells
KE:642Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.38KE:1287Glutathione synthesis
KE:1286Down Regulation, GSS and GSTs gene
KE:1284Up Regulation, SREBF2
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: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-0.2KE:1115Increase, Reactive oxygen species
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-0.4KE:1115Increase, Reactive oxygen species
KE:1445Increase, Lipid peroxidation
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-0.2KE:1115Increase, Reactive oxygen species
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary System Disease-0.4KE:795Increase, Regenerative cell proliferation (urothelial cells)
KE:177Mitochondrial dysfunction
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.5KE:1115Increase, Reactive oxygen species
KE:870Increase, Cell Proliferation
KE:1497Increased, recruitment of inflammatory cells
KE:1668Frustrated phagocytosis
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.33KE:1115Increase, Reactive oxygen species
KE:177Mitochondrial dysfunction
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.5KE:1262Apoptosis
KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1445Increase, Lipid peroxidation
KE:1115Increase, Reactive oxygen species
KE:1250Decrease, Lung function
KE:1239Altered, Gene Expression
KE:1993Increase, Pneumonia
KE:1497Increased, recruitment of inflammatory cells
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-0.38KE:1995Abnormal lipid metabolism
KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
KE:1931Intestinal barrier, disruption
KE:1198Activation, Macrophages
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal System Disease-0.38KE:1995Abnormal lipid metabolism
KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
KE:1931Intestinal barrier, disruption
KE:1198Activation, Macrophages
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder Development0.5KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
KE:2040Decrease, GLI1/2 target gene expression
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.19KE:1115Increase, Reactive oxygen species
KE:177Mitochondrial dysfunction
KE:1392Oxidative Stress
AOP:523Retinoic acid receptor agonism during neurodevelopment leading to microcephalyCongenital Nervous System Abnormality; Nervous System Disease-0.2KE:2201Agonism, Retinoic acid receptor
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.56KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:1262Apoptosis
KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
KE:285Reduction, Vitellogenin synthesis in liver
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular System Disease-0.31KE:1115Increase, Reactive oxygen species
KE:1493Increased Pro-inflammatory mediators
KE:1198Activation, Macrophages
KE:1392Oxidative Stress

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:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary System Disease-0.6KE:795Increase, Regenerative cell proliferation (urothelial cells)
KE:797Increase, Adenomas/carcinomas (urothelial)
KE:793Increase, Urinary bladder calculi
AOP:205AOP from chemical insult to cell deathUnclassified-0.67KE:1259narcosis
KE:177Mitochondrial dysfunction
KE:1262Apoptosis
KE:1263Necrosis
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed0.75KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.5KE:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.5KE:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.33KE:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.6KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.5KE:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.71KE:870Increase, Cell Proliferation
KE:1670Lung cancer
KE:1668Frustrated phagocytosis
KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-0.5KE:1115Increase, Reactive oxygen species
KE:1521Decrease, Growth
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-0.75KE:1115Increase, Reactive oxygen species
KE:1521Decrease, Growth
KE:1445Increase, Lipid peroxidation
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-0.5KE:1115Increase, Reactive oxygen species
KE:1521Decrease, Growth
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-0.67KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
KE:1521Decrease, Growth
KE:1505Cell cycle, disrupted
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-1.0KE:1521Decrease, Growth
KE:1505Cell cycle, disrupted
KE:1445Increase, Lipid peroxidation
KE:1115Increase, Reactive oxygen species
KE:1821Decrease, Cell proliferation
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:1521Decrease, Growth
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder Development0.6KE:1868Hyperinflammation
KE:1867Bradykinin system, hyperactivated
KE:1497Increased, recruitment of inflammatory cells
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.5KE:1250Decrease, Lung function
KE:1392Oxidative Stress
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-1.0KE:926Oxidation, Glutathione (To be considered with MIE)
KE:351Increased Mortality
KE:1445Increase, Lipid peroxidation
KE:1115Increase, Reactive oxygen species
KE:1607Increase, Necrosis
KE:759Increased, Kidney Failure
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory System Disease-0.33KE:1250Decrease, Lung function
KE:1392Oxidative Stress
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory System Disease-0.33KE:1250Decrease, Lung function
KE:1392Oxidative Stress
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular System Disease-0.5KE:1392Oxidative Stress
KE:177Mitochondrial dysfunction
KE:1919Increased, Cardiac Dysregulation
KE:1115Increase, Reactive oxygen species
KE:1929Increased incidence of cardiovascular morbidity and mortality in the general population
KE:1924Increased，Cardiac fibrosis
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.25KE:177Mitochondrial dysfunction
KE:1392Oxidative Stress
KE:759Increased, Kidney Failure
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.41KE:2001Cardiac hypertrophy
KE:1392Oxidative Stress
KE:1443Atherosclerosis
KE:1115Increase, Reactive oxygen species
KE:1929Increased incidence of cardiovascular morbidity and mortality in the general population
KE:1924Increased，Cardiac fibrosis
KE:1198Activation, Macrophages
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.55KE:1262Apoptosis
KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:177Mitochondrial dysfunction
KE:1115Increase, Reactive oxygen species
KE:2034liver dysfunction
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.44KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1392Oxidative Stress
KE:759Increased, Kidney Failure
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive Disorder-0.57KE:1115Increase, Reactive oxygen species
KE:1869Diminished protective oxidative stress response
KE:402Cognitive function, decreased
KE:1392Oxidative Stress
AOP:499Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter releaseDevelopmental Disorder Of Mental Health-1.0KE:2146Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2
KE:1339Increase, intracellular calcium
KE:341Impairment, Learning and memory
KE:2151Disruption, neurotransmitter release
AOP:500Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosisDevelopmental Disorder Of Mental Health-1.0KE:1262Apoptosis
KE:2146Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2
KE:177Mitochondrial dysfunction
KE:1115Increase, Reactive oxygen species
KE:352N/A, Neurodegeneration
KE:1339Increase, intracellular calcium
KE:341Impairment, Learning and memory
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-0.8KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:885Increase, Cancer
KE:1392Oxidative Stress
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
AOP:519Cardiac ion channels blockade leading to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-1.0KE:1961Prolongation of Action Potential Duration
KE:2282Cardiac ion channels blockade
KE:1929Increased incidence of cardiovascular morbidity and mortality in the general population
KE:2283Increased the early premature depolarizations during repolarization
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.4KE:2201Agonism, Retinoic acid receptor
KE:341Impairment, Learning and memory
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.4KE:2201Agonism, Retinoic acid receptor
KE:2231Locomotor function. Impaired
AOP:550Increased LMNA gene mutation leading to heart failureCardiovascular System Disease-1.0KE:2066Altered Signaling Pathways
KE:2279Structural changes in lamin A/C
KE:2278Increased LMNA Mutation
KE:1535Heart failure
KE:1924Increased，Cardiac fibrosis
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.