Benzo[a]pyrene

Benzo[a]pyrene



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:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-0.2KE:1264Increase, Nuclear receptor E75b gene expression
KE:1265Increase, Fushi tarazu factor-1 gene expression
AOP:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive System Disease; Endocrine System Disease; Reproductive System DiseaseUnder Review0.4KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous System DiseaseUnder Development0.22KE:295Induction, Upregulation of glucuronyltransferase activity
KE:756Hippocampal gene expression, Altered
AOP:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic DiseaseWPHA/WNT Endorsed0.25KE:155Inadequate DNA repair
AOP:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:1703Dysregulation of heart rate and vascular tone
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive System DiseaseUnder Review0.5KE:1690Decrease, circulating testosterone levels
KE:413Reduction, Testosterone synthesis in Leydig cells
KE:266Decrease, Steroidogenic acute regulatory protein (STAR)
KE:289Decrease, Translocator protein (TSPO)
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:28Cyclooxygenase inhibition leading reproductive failureReproductive System Disease-0.17KE:49Reduction, Ca and HCO3 transport to shell gland
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:140Decreased, HSD17B10 expression
KE:179Decreased, Mitochondrial fatty acid beta-oxidation
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal System DiseaseWPHA/WNT Endorsed0.14KE:1493Increased Pro-inflammatory mediators
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:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.38KE:458Increased, De Novo FA synthesis
KE:463Up Regulation, FAS
KE:54Up Regulation, CD36
KE:454Increased, Triglyceride formation
KE:462Up Regulation, SCD-1
KE:451Inhibition, Mitochondrial fatty acid beta-oxidation
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.5KE:179Decreased, Mitochondrial fatty acid beta-oxidation
KE:454Increased, Triglyceride formation
KE:54Up Regulation, CD36
KE:462Up Regulation, SCD-1
KE:474Down Regulation, HMGCS2
KE:472Down Regulation, CPT1A
AOP:73Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundityUnclassified-0.23KE:528Decreased, Synthesis of NE
KE: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-0.14KE: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:104Altered ion channel activity leading impaired heart functionUnclassified-0.25KE:699Increased, cardiac arrthymia
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary System Disease-0.17KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory System Disease-0.2KE:734Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine System Disease-0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive System Disease; Cancer-0.33KE:111Agonism, Estrogen receptor
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: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-0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1690Decrease, circulating testosterone levels
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary System Disease-0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP: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:126Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulationUnclassified-0.15KE:10059Decreased LH surge for 24 hours
KE:531Decreased, LH Surge
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal System DiseaseUnder Review0.11KE:1493Increased Pro-inflammatory mediators
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-0.43KE:1066Promotion, SIX-1 postive basal-type progenitor cells
KE:1067Proliferation/Clonal Expansion, aberrant basal cells
KE:1065Activation, estrogen receptor alpha
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:194Hepatic nuclear receptor activation leading to altered amphibian metamorphosisUnclassified-0.17KE:295Induction, Upregulation of glucuronyltransferase activity
AOP:1955-hydroxytryptamine transporter (5-HTT) inhibition leading to population increaseUnclassified-0.12KE:1163Increased, Reproductive Success
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:1281Increased, DNA Damage-Repair
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
KE:1280Activation, HIF-1
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: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:232NFE2/Nrf2 repression to steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.12KE:1419Reduced, FXR activity
AOP:258Renal protein alkylation leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder Development0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal System Disease; Respiratory System Disease-0.14KE:149Increase, Inflammation
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine System Disease-0.25KE:1614Decrease, androgen receptor activation
KE:1690Decrease, circulating testosterone levels
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder Development0.17KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:297Inhibition of retinaldehyde dehydrogenase leads to population declineUnclassifiedUnder Development0.17KE:1643Altered, Visual function
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 Development0.4KE:1614Decrease, androgen receptor activation
KE: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:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.18KE:592Reduced, survival
KE:10042Abnormal development
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary System Disease-0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:337DNA methyltransferase inhibition leading to population decline (2)Unclassified-0.12KE:1776Increase, Ovarian somatic cell apoptosis
AOP:339DNA methyltransferase inhibition leading to population decline (4)Unclassified-0.12KE:1776Increase, Ovarian somatic cell apoptosis
AOP:341DNA methyltransferase inhibition leading to transgenerational effects (2)Physical Disorder-0.11KE:1783Increase, Ovarian somatic cell apoptosis (F3)
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:348Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectoryUnclassifiedUnder Development0.2KE:1758Impaired, Spermatogenesis
AOP:349Inhibition of 11β-hydroxylase leading to decresed population trajectoryUnclassifiedUnder Development0.12KE:1798Decreased spermatogenesis
AOP:362Immune mediated hepatitisGastrointestinal System Disease; Immune System Disease-0.12KE:1817Apoptotic cell death
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder Review0.12KE:1643Altered, Visual function
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:1643Altered, Visual function
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:1643Altered, Visual function
AOP:368Cytochrome oxidase inhibition leading to increased nasal lesionsUnclassified-0.33KE:1825Increase, Cell death
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:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular System DiseaseUnder Development0.14KE:1869Diminished protective oxidative stress response
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:388Deposition of ionising energy leading to population decline via programmed cell deathReproductive System Disease-0.2KE:1864Increase, Programmed cell death
AOP:397Bulky DNA adducts leading to mutationsGenetic DiseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:398Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogoniaReproductive System DiseaseUnder Development0.17KE:1883Decreased, size of the ovarian reserve
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-0.25KE:1821Decrease, Cell proliferation
KE:1643Altered, Visual function
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-0.1KE:1825Increase, Cell death
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-0.33KE:1115Increase, Reactive oxygen species
KE:1607Increase, Necrosis
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic System Disease; Cancer-0.36KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
KE:1493Increased Pro-inflammatory mediators
KE:403Suppression, Immune system
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary System DiseaseUnder Development0.2KE:1392Oxidative Stress
AOP:441Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiationCongenital Nervous System Abnormality; Nervous System Disease-0.29KE:1974Activation of Tumor Protein 53
KE:1262Apoptosis
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.33KE:1365Increase, Apoptosis
KE:1798Decreased spermatogenesis
KE:1392Oxidative Stress
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous System Disease-0.29KE:352N/A, Neurodegeneration
KE:1392Oxidative Stress
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory System Disease-0.27KE:1262Apoptosis
KE:2013Airway remodeling
KE:1392Oxidative Stress
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited Metabolic Disorder-0.33KE:2120Superoxide generation, increased
KE:1392Oxidative Stress
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder Development0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
KE:2040Decrease, GLI1/2 target gene expression
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 Development0.14KE:1392Oxidative Stress
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular System Disease; Thoracic DiseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal System DiseaseUnder Review0.29KE:1825Increase, Cell death
KE:1392Oxidative Stress
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive System Disease-0.2KE:1115Increase, Reactive oxygen species
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-0.3KE:1690Decrease, circulating testosterone levels
KE:286Altered, Transcription of genes by the androgen receptor
KE:219Reduction, Plasma 17beta-estradiol concentrations
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:1365Increase, Apoptosis
KE:1392Oxidative Stress
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular System Disease-0.2KE:2165Activation of PPAR
KE:1392Oxidative Stress
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:54Up Regulation, CD36
AOP:518Liver X Receptor (LXR) activation leads to liver steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.2KE:89Synthesis, De Novo Fatty Acid (FA)
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:179Decreased, Mitochondrial fatty acid beta-oxidation
KE:2224Dysregulation of transcriptional expression within PPAR signaling network
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:556Decreased Na/K ATPase activity leading to heart failureCardiovascular System Disease-0.17KE:389Increased, Intracellular Calcium overload
AOP:558Phosphodiesterase inhibition leading to heart failureCardiovascular System Disease-0.17KE:389Increased, Intracellular Calcium overload
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
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory System Disease-0.33KE:1825Increase, Cell death
AOP:574Inhibition, cytochrome oxidase leads to Loss of olfactory functionUnclassified-0.33KE:1825Increase, Cell death

Associated AOPs with Level of Relevance 2
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:3Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficitsNervous System DiseaseWPHA/WNT Endorsed0.14KE:896Parkinsonian motor deficits
AOP:6Antagonist binding to PPARα leading to body-weight lossSymptomWPHA/WNT Endorsed0.38KE:863Increased, Catabolism of Muscle Protein
KE:1528Fatty Acid Beta Oxidation, Decreased
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 Endorsed0.5KE:52Decreased, Calcium influx
KE:381Reduced levels of BDNF
KE: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 Endorsed0.4KE:382Aberrant, Dendritic morphology
KE:52Decreased, Calcium influx
KE:341Impairment, Learning and memory
KE:381Reduced levels of BDNF
AOP:17Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memoryDevelopmental Disorder Of Mental HealthWPHA/WNT Endorsed0.3KE:1493Increased Pro-inflammatory mediators
KE:341Impairment, Learning and memory
KE:1392Oxidative Stress
AOP:34LXR activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.31KE:89Synthesis, De Novo Fatty Acid (FA)
KE:54Up Regulation, CD36
KE:258Activation, SCD-1
KE: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:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
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 Endorsed0.33KE:389Increased, Intracellular Calcium overload
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:63Cyclooxygenase inhibition leading to reproductive dysfunctionReproductive System Disease-0.2KE:675Reduced, Reproductive Success
AOP:91Sodium channel inhibition leading to reduced survivalUnclassified-0.17KE:592Reduced, survival
AOP:95Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survivalUnclassified-0.17KE:592Reduced, survival
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-0.29KE:636Decreased, survival
KE:341Impairment, Learning and memory
AOP:100Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behaviorReproductive System Disease-0.29KE:675Reduced, Reproductive Success
KE:672Reduced, Prostaglandin F2alpha synthesis, ovary
AOP:101Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone releaseReproductive System Disease-0.29KE:675Reduced, Reproductive Success
KE:681Decreased, Prostaglandin F2alpha synthesis, ovary
AOP:102Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transitionReproductive System Disease-0.2KE:675Reduced, Reproductive Success
KE:690Reduced, Luteinizing hormone (LH), plasma
AOP:103Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpointReproductive System Disease-0.3KE:675Reduced, Reproductive Success
KE:690Reduced, Luteinizing hormone (LH), plasma
KE:696Increased, Chromosome misseggregation
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-0.33KE:719Increase, hepatocellular adenomas and carcinomas
KE:769Increase, Oxidative metabolism
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-0.5KE:330Decrease, Fertility
KE:1690Decrease, circulating testosterone levels
KE:807Decreased, cholesterol
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.22KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign Neoplasm; Respiratory System DiseaseUnder Review0.43KE:870Increase, Cell Proliferation
KE:868Increase, Tissue Degeneration, Necrosis & Atrophy
KE:872Increase, Site of Contact Nasal Tumors
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 Development0.2KE:952Hypertension
KE:933KE6 : Depletion, Nitric Oxide
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory System Disease-0.22KE:1226Increased Respiratory irritability and Chronic Cough,
KE:1218Opening of calcium channel, Calcium influx
AOP:2035-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population declineReproductive System Disease-0.12KE:1141Decreased, Reproductive Success
AOP:2045-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increaseUnclassified-0.12KE:1163Increased, Reproductive Success
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-0.43KE:1514Neurodegeneration
KE:1513General Apoptosis
KE:1392Oxidative Stress
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development
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:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous System Disease-0.2KE:389Increased, Intracellular Calcium overload
KE:352N/A, Neurodegeneration
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-0.75KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
KE:1521Decrease, Growth
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-0.75KE:1825Increase, Cell death
KE:1771Decrease, Adenosine triphosphate pool
KE:1521Decrease, Growth
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-0.75KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
KE:1521Decrease, Growth
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-0.75KE:1825Increase, Cell death
KE:1771Decrease, Adenosine triphosphate pool
KE: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 Development0.4KE: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:303Frustrated phagocytosis-induced lung cancerCancerUnder Development0.71KE:1669Increased, DNA damage and mutation
KE:870Increase, Cell Proliferation
KE:1670Lung cancer
KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
AOP:304TBX1 inhibition leading to congenital cardiac conotruncal anomaliesCardiovascular System Disease-0.17KE:1685Anomalies, Congenital cardiac conotruncal
AOP:322Alkylation of DNA leading to reduced sperm countReproductive System Disease-0.6KE:1757Reduce, Sperm count
KE:155Inadequate DNA repair
KE:1365Increase, Apoptosis
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-0.5KE:2147Decreased, Viable Offspring
KE:807Decreased, cholesterol
KE:1758Impaired, Spermatogenesis
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:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.75KE:1669Increased, DNA damage and mutation
KE:870Increase, Cell Proliferation
KE:1896Genomic instability
KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
KE:1090Increased, mesotheliomas
AOP:442Binding to voltage gate sodium channels during development leads to cognitive impairmentCognitive DisorderUnder Review0.14KE:402Cognitive function, decreased
AOP:449Ceramide synthase inhibition leading to neural tube defectsNeural Tube Defect-0.14KE:1561Neural tube defects
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-0.56KE:1669Increased, DNA damage and mutation
KE:870Increase, Cell Proliferation
KE:1670Lung cancer
KE:1115Increase, Reactive oxygen species
KE:1497Increased, recruitment of inflammatory cells
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous System Disease-0.21KE:1825Increase, Cell death
KE:389Increased, Intracellular Calcium overload
KE:896Parkinsonian motor deficits
KE:1392Oxidative Stress
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.38KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
KE:1825Increase, Cell death
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 Development0.25KE:389Increased, Intracellular Calcium overload
KE: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-0.09KE: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:498Increased LCN2/iron complex leading to neurological disordersNervous System Disease-0.5KE: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:501Excessive iron accumulation leading to neurological disordersNervous System Disease-0.5KE:2150Neurological disorder
KE:1392Oxidative Stress
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-0.33KE:1065Activation, estrogen receptor alpha
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.2KE:341Impairment, Learning and memory
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-0.57KE:1115Increase, Reactive oxygen species
KE:2147Decreased, Viable Offspring
KE:1758Impaired, Spermatogenesis
KE:1392Oxidative Stress
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental Disorder Of Mental Health-0.08KE:341Impairment, Learning and memory
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-0.56KE:389Increased, Intracellular Calcium overload
KE:2233Decreased, ERαβ heterodimers
KE:1262Apoptosis
KE:1392Oxidative Stress
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:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-0.2KE:1065Activation, estrogen receptor alpha
AOP:562HCN Channel Inhibition leading to ArrhythmiasSymptom-0.2KE:1106Occurrence, cardiac arrhythmia
AOP:572Imidacloprid-Induced BMP4 inhibition Leading to Neural Tube Closure DefectsNeural Tube Defect-0.2KE:1561Neural tube defects

Associated AOPs with Level of Relevance 3
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal System DiseaseUnder Development0.5KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:288Activation of specific nuclear receptors, Transcriptional change
KE:41Inhibition, Bile Salt Export Pump (ABCB11)
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder Review0.33KE:112Antagonism, Estrogen receptor
KE:285Reduction, Vitellogenin synthesis in liver
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal System DiseaseUnder Review0.8KE:854Alterations, Cellular proliferation / hyperplasia
KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:62AKT2 activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.25KE:486systemic inflammation leading to hepatic steatosis
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive System Disease-0.71KE:520Decreased sperm quantity or quality in the adult, Decreased fertility
KE:494Glucocorticoid Receptor Agonist, Activation
KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
KE:413Reduction, Testosterone synthesis in Leydig cells
KE:1690Decrease, circulating testosterone levels
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:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive System Disease-0.2KE:1614Decrease, androgen receptor activation
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-0.55KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:801modulation, Unknown
KE:802Increased, HIF-1 alpha transcription
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:285Reduction, Vitellogenin synthesis in liver
KE:799Increased, HIF-1 heterodimer
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited Metabolic DisorderWPHA/WNT Endorsed0.33KE:18Activation, AhR
KE:850Induction, CYP1A2/CYP1A5
AOP:151AhR activation leading to preeclampsiaCardiovascular System DiseaseUnder Development0.43KE:18Activation, AhR
KE:1892increase, placental insufficiency
KE:948reduced production, VEGF
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal System Disease-0.5KE:1287Glutathione synthesis
KE:1286Down Regulation, GSS and GSTs gene
KE:1285Up Regulation, Unsaturated fatty acid
KE:1284Up Regulation, SREBF2
AOP:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder Review0.25KE:1115Increase, Reactive oxygen species
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-0.33KE:18Activation, AhR
KE:285Reduction, Vitellogenin synthesis in liver
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:318Glucocorticoid Receptor activation leading to hepatic steatosisGastrointestinal System Disease; Inherited Metabolic Disorder-0.4KE:860Decreased, Mitochondrial Fatty Acid Beta Oxidation
KE:122Activation, Glucocorticoid Receptor
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-0.4KE:1115Increase, Reactive oxygen species
KE:1365Increase, Apoptosis
AOP:334Glucocorticoid Receptor Agonism Leading to Impaired Fin RegenerationUnclassified-0.17KE:122Activation, Glucocorticoid Receptor
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE: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 Development0.5KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine System Disease; Reproductive System Disease; Cancer-0.6KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:18Activation, AhR
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal System Disease; Respiratory System Disease-0.2KE:18Activation, AhR
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular System Disease-0.25KE:1115Increase, Reactive oxygen species
KE:1919Increased, Cardiac Dysregulation
KE:1392Oxidative Stress
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic Disease; CancerUnder Development0.56KE:18Activation, AhR
KE:1262Apoptosis
KE:149Increase, Inflammation
KE:1971Increased, tumor growth
KE:1241Increased, Motility
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic Disease; CancerUnder Development0.4KE:1669Increased, DNA damage and mutation
KE:1554Increase Chromosomal Aberrations
KE:155Inadequate DNA repair
KE:112Antagonism, Estrogen receptor
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive System Disease-0.12KE:1065Activation, estrogen receptor alpha
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory System Disease-0.45KE:18Activation, AhR
KE:1262Apoptosis
KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:1250Decrease, Lung function
KE:1239Altered, Gene Expression
KE:1497Increased, recruitment of inflammatory cells
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary System Disease-0.25KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
KE:1365Increase, Apoptosis
KE:1392Oxidative Stress
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular System Disease-0.24KE:1443Atherosclerosis
KE:1115Increase, Reactive oxygen species
KE:2001Cardiac hypertrophy
KE:1392Oxidative Stress
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:1392Oxidative Stress
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal System Disease-0.15KE:1115Increase, Reactive oxygen species
KE:1392Oxidative Stress
AOP:472DNA adduct formation leading to kidney failureUrinary System Disease-0.44KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:1825Increase, Cell death
KE:1392Oxidative Stress
AOP:477Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspringPhysical Disorder-0.67KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
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:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired Metabolic Disease-0.3KE:2126Estrogen receptor alpha inactivation
KE:1497Increased, recruitment of inflammatory cells
KE:2125Increased fat mass
AOP:494AhR activation leading to liver fibrosisGastrointestinal System Disease-0.17KE:18Activation, AhR
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular System Disease-0.12KE:1115Increase, Reactive oxygen species
KE:1392Oxidative Stress
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.33KE:307Increase, Vitellogenin synthesis in liver
KE:111Agonism, Estrogen receptor
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.6KE:307Increase, Vitellogenin synthesis in liver
KE:111Agonism, Estrogen receptor
KE:364Impaired development of, Reproductive organs
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-0.23KE:1115Increase, Reactive oxygen species
KE:1493Increased Pro-inflammatory mediators
KE:1392Oxidative Stress
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive System Disease; Endocrine System Disease-0.5KE:18Activation, AhR
KE:1262Apoptosis
KE:1883Decreased, size of the ovarian reserve

Associated AOPs with Level of Relevance 5
AOP Identifier AOP Title AO Classification OECD Status Coverage Score KE Identifier KE Name
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive System Disease-0.6KE:26Antagonism, Androgen receptor
KE:286Altered, Transcription of genes by the androgen receptor
KE:337N/A, Impairment of reproductive capacity
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT Endorsed0.8KE:18Activation, AhR
KE:317Altered, Cardiovascular development/function
KE:1269Increase, COX-2 expression
KE:947Increase, Early Life Stage Mortality
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:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT Endorsed0.57KE:18Activation, AhR
KE:317Altered, Cardiovascular development/function
KE:947Increase, Early Life Stage Mortality
KE:948reduced production, VEGF
AOP:205AOP from chemical insult to cell deathUnclassified-0.5KE:1259narcosis
KE:1262Apoptosis
KE:1263Necrosis
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT Endorsed1.0KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1521Decrease, Growth
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.75KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1521Decrease, Growth
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 Development0.5KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1521Decrease, Growth
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:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal System DiseaseUnder Review0.5KE:1651Treatment-resistant gastric cancer
KE:1115Increase, Reactive oxygen species
KE:1753Chronic reactive oxygen species
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-0.5KE:1115Increase, Reactive oxygen species
KE:1521Decrease, Growth
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-0.8KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
KE:1521Decrease, Growth
KE:1505Cell cycle, disrupted
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-1.0KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1821Decrease, Cell proliferation
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory System Disease-0.5KE:1250Decrease, Lung function
KE:1392Oxidative Stress
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.67KE:18Activation, AhR
KE:1115Increase, Reactive oxygen species
KE:1670Lung cancer
KE:1669Increased, DNA damage and mutation
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.8KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1670Lung cancer
KE:1669Increased, DNA damage and mutation
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory System Disease-1.0KE:18Activation, AhR
KE:1115Increase, Reactive oxygen species
KE:1250Decrease, Lung function
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1825Increase, Cell death
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory System Disease-1.0KE:18Activation, AhR
KE:1250Decrease, Lung function
KE:1262Apoptosis
KE:1923Altered gene expression, P53 dependent apoptosis pathway
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-1.0KE:18Activation, AhR
KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
KE:1670Lung cancer
KE:870Increase, Cell Proliferation
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.33KE:1115Increase, Reactive oxygen species
KE:1817Apoptotic cell death
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: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 Development0.22KE:2092Promotion, Ovarian Cancer
KE:1046Suppression, Estrogen receptor (ER) activity
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal System DiseaseUnder Review0.67KE:18Activation, AhR
KE:947Increase, Early Life Stage Mortality
KE:2020Decrease, sox9 expression
KE:2021Increase, slincR expression
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder Review0.83KE:18Activation, AhR
KE:947Increase, Early Life Stage Mortality
KE:2020Decrease, sox9 expression
KE:2021Increase, slincR expression
KE:317Altered, Cardiovascular development/function
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.5KE:18Activation, AhR
KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
KE:295Induction, Upregulation of glucuronyltransferase activity
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive Disorder-0.56KE:18Activation, AhR
KE:850Induction, CYP1A2/CYP1A5
KE:1392Oxidative Stress
KE:402Cognitive function, decreased
KE:756Hippocampal gene expression, Altered
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal System Disease-0.45KE:1262Apoptosis
KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:2034liver dysfunction
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: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:2126Estrogen receptor alpha inactivation
KE:179Decreased, Mitochondrial fatty acid beta-oxidation
KE:1115Increase, Reactive oxygen species
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive System Disease; CancerUnder Review0.5KE:1896Genomic instability
KE:2154Uterine adenocarcinoma (endometrioid adenocarcinoma Type I)
KE:1065Activation, estrogen receptor alpha
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-1.0KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
KE:885Increase, Cancer
KE:1513General Apoptosis
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-0.8KE:1513General Apoptosis
KE: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.