Fenvalerate


Associated AOPs with Level of Relevance - 1 AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

AOP Identifier AOP Title AO Classification OECD Status Taxonomic applicability Coverage Score The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.12KE:1690Decrease, circulating testosterone levels
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal system diseaseUnder DevelopmentHumans0.12KE:1115Increase, Reactive oxygen species
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory system diseaseUnder DevelopmentHuman, Mouse0.2KE:272Activation/Proliferation, T-cells
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary system diseaseWPHA/WNT EndorsedMouse, Human0.2KE:272Activation/Proliferation, T-cells
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.6KE: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-Human, Mouse, Rat0.06KE:454Increased, Triglyceride formation
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.08KE:454Increased, Triglyceride formation
AOP:63Cyclooxygenase inhibition leading to reproductive dysfunctionReproductive system disease-Goldfish, Human, Mouse, Rat0.2KE:685Reduced, Prostaglandins, ovary
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.29KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
KE:1690Decrease, circulating testosterone levels
AOP:77Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1Unclassified-Honey bee0.14KE: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-Honey bee0.12KE:341Impairment, Learning and memory
AOP:87Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failureUnclassified-Honey bee0.12KE: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-Honey bee0.14KE:341Impairment, Learning and memory
AOP:89Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failureUnclassified-Honey bee0.12KE: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-Honey bee0.12KE:341Impairment, Learning and memory
AOP:99Histamine (H2) receptor antagonism leading to reduced survivalUnclassified-Zebrafish0.14KE:341Impairment, Learning and memory
AOP:100Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behaviorReproductive system disease-Goldfish0.14KE:672Reduced, Prostaglandin F2alpha synthesis, ovary
AOP:101Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone releaseReproductive system disease-Goldfish0.14KE:681Decreased, Prostaglandin F2alpha synthesis, ovary
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.17KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal system diseaseUnder ReviewRattus norvegicus, Mus musculus0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory system disease-Mus musculus0.2KE: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-Rattus norvegicus, Mus musculus0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus0.2KE:754Increased, Luteinizing hormone (LH)
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:749Decreased, Progesterone from corpus luteum
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-Rattus norvegicus0.17KE:778Increase, Regenerative cell proliferation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-Mus musculus, Rattus norvegicus0.2KE:781Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.25KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.25KE:716Increase, cell proliferation (hepatocytes)
AOP:119Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)Cancer; Endocrine system disease-Rattus norvegicus, Mus musculus0.14KE:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus, Mus musculus0.4KE:791Increased, Leutinizing hormone (LH)
KE:1690Decrease, circulating testosterone levels
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary system disease-Mus musculus, Rattus norvegicus0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign neoplasm; Respiratory system diseaseUnder Review0.14KE:870Increase, Cell Proliferation
AOP:155Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedFathead minnow, Zebrafish0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:156Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:157Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:158Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive system disease-CD-1 mouse, SD rat0.17KE:1042Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1067Proliferation/Clonal Expansion, aberrant basal cells
AOP:189Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.5KE:1116Decreased, Triiodothyronine (T3) in tissues
KE:1003Decreased, Triiodothyronine (T3)
AOP:190Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.33KE:1828Increased, Thyroxine (T4) in serum
KE:1116Decreased, Triiodothyronine (T3) in tissues
AOP:191Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.25KE:1154Increased, Triiodothyronine (T3) in tissues
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory system disease-0.11KE:1218Opening of calcium channel, Calcium influx
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.25KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.17KE:1262Apoptosis
AOP:213Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)Gastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.17KE:1115Increase, Reactive oxygen species
AOP:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-Japanese quail, Cynops pyrrhogaster0.17KE:1390Sexual behavior, decreased
AOP:238Deposition of energy leading to population decline via DNA strand breaks and oocyte apoptosisUnclassified-Mice, Daphnia magna0.17KE:1775Increase, Oocyte apoptosis
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:870Increase, Cell Proliferation
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural tube defect-0.2KE:1239Altered, Gene Expression
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous system disease-0.1KE:389Increased, Intracellular Calcium overload
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine system disease-Human, Rat0.12KE:1690Decrease, circulating testosterone levels
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder DevelopmentMammals0.29KE:870Increase, Cell Proliferation
KE:1115Increase, Reactive oxygen species
AOP:309Luteinizing hormone receptor antagonism leading to reproductive dysfunctionUnclassified-Fish0.29KE:1693Reduction, Plasma progesterone concentration
KE:1692Reduction, Progesterone synthesis
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-Daphnia magna, Fish0.29KE:1775Increase, Oocyte apoptosis
KE:1115Increase, Reactive oxygen species
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.09KE:10042Abnormal development
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.2KE:1365Increase, Apoptosis
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-Teleost fish0.33KE:1758Impaired, Spermatogenesis
KE:807Decreased, cholesterol
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary system disease-Rat0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:336DNA methyltransferase inhibition leading to population decline (1)Unclassified-Daphnia magna0.14KE:1775Increase, Oocyte apoptosis
AOP:338DNA methyltransferase inhibition leading to population decline (3)Unclassified-0.14KE:1775Increase, Oocyte apoptosis
AOP:348Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectoryUnclassifiedUnder DevelopmentFish0.2KE:1758Impaired, Spermatogenesis
AOP:349Inhibition of 11β-hydroxylase leading to decresed population trajectoryUnclassifiedUnder DevelopmentFish0.12KE:1798Decreased spermatogenesis
AOP:362Immune mediated hepatitisGastrointestinal system disease; Immune system disease-Homo sapiens, Rat0.12KE:1817Apoptotic cell death
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder ReviewZebrafish0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:366Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosisUnclassified-0.14KE:959Increased, Free serum thyroxine (T4)
AOP:367Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosisUnclassified-0.14KE:959Increased, Free serum thyroxine (T4)
AOP:368Cytochrome oxidase inhibition leading to increased nasal lesionsUnclassified-Rodents, Human0.33KE:1825Increase, Cell death
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-Lemna minor, Chlamydomonas reinhardtii0.12KE:1115Increase, Reactive oxygen species
AOP:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive system disease-Lemna minor0.12KE:1115Increase, Reactive oxygen species
AOP:388Deposition of ionising energy leading to population decline via programmed cell deathReproductive system disease-Lemna minor0.2KE:1864Increase, Programmed cell death
AOP:398Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogoniaReproductive system diseaseUnder DevelopmentMouse, Rat, Human0.33KE:1882Disrupted, initiation of meiosis of oogonia in the ovary
KE:405disrupted, ovarian cycle
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-Zebrafish0.12KE:1821Decrease, Cell proliferation
AOP:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.25KE:870Increase, Cell Proliferation
KE:1115Increase, Reactive oxygen species
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-Zebrafish0.1KE:1825Increase, Cell death
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-Fish, Mice0.17KE:1115Increase, Reactive oxygen species
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1115Increase, Reactive oxygen species
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.4KE:1825Increase, Cell death
KE:1115Increase, Reactive oxygen species
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.25KE:1262Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:870Increase, Cell Proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.09KE:870Increase, Cell Proliferation
AOP:441Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiationCongenital nervous system abnormality; Nervous system disease-Homo sapiens, Mus musculus musculus, Rattus norvegicus0.14KE:1262Apoptosis
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.22KE:1798Decreased spermatogenesis
KE:1365Increase, Apoptosis
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.08KE:1365Increase, Apoptosis
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.22KE:870Increase, Cell Proliferation
KE:1115Increase, Reactive oxygen species
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.09KE:1262Apoptosis
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.22KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous system disease-0.11KE:1825Increase, Cell death
KE:389Increased, Intracellular Calcium overload
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.12KE:1825Increase, Cell death
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE:870Increase, Cell Proliferation
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal system diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys0.14KE:1825Increase, Cell death
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive system disease-Mammals, Fish0.2KE:1115Increase, Reactive oxygen species
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.1KE:2125Increased fat mass
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.22KE:854Alterations, Cellular proliferation / hyperplasia
KE:1183Decreased, Apoptosis (Epithelial Cells)
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.1KE:1690Decrease, circulating testosterone levels
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-0.12KE:1115Increase, Reactive oxygen species
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-Mammals0.33KE:2251Estradiol availability, increased
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular system disease-0.14KE:1365Increase, Apoptosis
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.29KE:1758Impaired, Spermatogenesis
KE:1115Increase, Reactive oxygen species
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2229Cerebellar neuronal differentiation. Decreased
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-Human and other cells in culture, Rodents, Dog, Pig, Zebrafish0.17KE:389Increased, Intracellular Calcium overload
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-Vertebrates0.4KE:2294Plasma estradiol, increased
KE:2251Estradiol availability, increased
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive system disease; Endocrine system disease-Rat, Mouse, Zebra fish, Human0.17KE:1262Apoptosis
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental disorder of mental health-0.17KE:1115Increase, Reactive oxygen species
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory system disease-Rodents, Humans0.33KE:1825Increase, Cell death
AOP:574Inhibition, cytochrome oxidase leads to Loss of olfactory functionUnclassified-Rodents, Humans0.33KE:1825Increase, Cell death

Associated AOPs with Level of Relevance - 2 AOPs with at least 1 AO associated with chemical, and no associated MIE

AOP Identifier AOP Title AO Classification OECD Status Taxonomic applicability Coverage Score The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
AOP:6Antagonist binding to PPARα leading to body-weight lossSymptomWPHA/WNT EndorsedMus musculus, Homo sapiens, Pimephales promelas, Colinus virginianus, Rattus norvegicus0.12KE:864Decreased, Body Weight
AOP:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive system disease; Endocrine system disease; Reproductive system diseaseUnder ReviewRat, Mouse, Human0.2KE:405disrupted, ovarian cycle
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 EndorsedMonkey, Rat, Human, Mouse, Zebrafish0.25KE:52Decreased, Calcium influx
KE:341Impairment, Learning and memory
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 EndorsedHuman, Mouse, Monkey sp., Rat0.2KE:52Decreased, Calcium influx
KE:341Impairment, Learning and memory
AOP:17Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memoryDevelopmental disorder of mental healthWPHA/WNT EndorsedRat, Mouse, Human0.1KE:341Impairment, Learning and memory
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.2KE:337N/A, Impairment of reproductive capacity
AOP:34LXR activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.08KE:345N/A, Liver Steatosis
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderWPHA/WNT EndorsedHuman, Rat, Mouse0.12KE:402Cognitive function, decreased
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 EndorsedHuman, Mouse, Rat0.22KE:389Increased, Intracellular Calcium overload
KE:341Impairment, Learning and memory
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental disorder of mental healthWPHA/WNT EndorsedHomo sapiens, Rattus sp.0.1KE:341Impairment, Learning and memory
AOP:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive system disease-Rattus rattus0.5KE:807Decreased, cholesterol
KE:1690Decrease, circulating testosterone levels
KE:330Decrease, Fertility
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Homo sapiens0.11KE:402Cognitive function, decreased
AOP:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.25KE:885Increase, Cancer
AOP:205AOP from chemical insult to cell deathUnclassified-Vertebrates0.17KE:1262Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.4KE:1395Liver Cancer
KE:1393Hepatocytotoxicity
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-Lemna minor, Lemna gibba0.09KE:1521Decrease, Growth
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.5KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.25KE:1521Decrease, Growth
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.25KE:1521Decrease, Growth
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.17KE:1521Decrease, Growth
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.4KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.25KE:1521Decrease, Growth
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.5KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.5KE:1825Increase, Cell death
KE:1521Decrease, Growth
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.5KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-Daphnia magna0.5KE:1825Increase, Cell death
KE:1521Decrease, Growth
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder DevelopmentRattus rattus, Mus musculus0.22KE: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 Development0.22KE:1193N/A, Breast Cancer
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderUnder DevelopmentHuman, Mouse0.2KE:402Cognitive function, decreased
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine system disease; Reproductive system disease; Reproductive system diseaseUnder DevelopmentMammals0.17KE:405disrupted, ovarian cycle
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary system disease-0.33KE:1603Chronic kidney disease
KE:1115Increase, Reactive oxygen species
AOP:405Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive functionCognitive disorder-Rattus norvegicus, Mus musculus, Homo sapiens0.2KE:402Cognitive function, decreased
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.33KE:1982metastatic breast cancer
KE:1971Increased, tumor growth
KE:1262Apoptosis
AOP:442Binding to voltage gate sodium channels during development leads to cognitive impairmentCognitive disorderUnder ReviewRattus norvegicus, Mouse, Humans0.14KE:402Cognitive function, decreased
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic disease; CancerUnder DevelopmentHuman and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast0.1KE:1982metastatic breast cancer
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Mouse, Monkey, Human0.12KE:402Cognitive function, decreased
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.11KE:402Cognitive function, decreased
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE: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 DevelopmentMouse, Rat, Human, Caenorhabditis elegans0.25KE:389Increased, Intracellular Calcium overload
KE:341Impairment, Learning and memory
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental disorder of mental healthUnder ReviewMouse, Rat, Rabbit, Dog, Pigs, Cow, Human0.12KE:341Impairment, Learning and memory
AOP:485Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognitionCognitive disorder-Human0.14KE:402Cognitive function, decreased
AOP:486Binding to the extracellular protein laminin leading to decreased cognitive functionCognitive disorder-Human0.14KE: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:498Increased LCN2/iron complex leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
AOP:499Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter releaseDevelopmental disorder of mental health-Rattus norvegicus, Mus musculus, Homo sapiens0.5KE:1339Increase, intracellular calcium
KE: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-Rattus norvegicus, Mus musculus, Homo sapiens0.57KE:1339Increase, intracellular calcium
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
KE:341Impairment, Learning and memory
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive system disease; CancerUnder ReviewHuman, Mouse0.33KE:2154Uterine adenocarcinoma (endometrioid adenocarcinoma Type I)
KE:2152Epigenetic modification process
AOP:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-Mouse, Rat, Human0.2KE:341Impairment, Learning and memory
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.33KE:1239Altered, Gene Expression
KE:341Impairment, Learning and memory
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.33KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.33KE:389Increased, Intracellular Calcium overload
KE:1262Apoptosis
KE:341Impairment, Learning and memory
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-Human and other cells in culture0.2KE:885Increase, Cancer

Associated AOPs with Level of Relevance - 3 AOPs with at least 1 MIE associated with chemical, and no associated AO

AOP Identifier AOP Title AO Classification OECD Status Taxonomic applicability Coverage Score The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
AOP:69Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig CellReproductive system disease-Rattus norvegicus, Homo sapiens0.2KE:642Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.5KE:786Increase, Cytotoxicity (hepatocytes)
KE:787Increase, Regenerative cell proliferation (hepatocytes)
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.12KE:1286Down Regulation, GSS and GSTs gene
AOP:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder ReviewHuman0.25KE:1115Increase, Reactive oxygen species
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal system diseaseUnder ReviewHomo sapiens0.17KE:1115Increase, Reactive oxygen species
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-Daphnia magna0.4KE:1115Increase, Reactive oxygen species
KE:1769Increase, Body fluid overload
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-Daphnia magna0.2KE:1115Increase, Reactive oxygen species
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-Daphnia magna, Paracyclopina nana0.2KE:1115Increase, Reactive oxygen species
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-Daphnia magna0.4KE:1365Increase, Apoptosis
KE:1115Increase, Reactive oxygen species
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular system disease-0.08KE:1115Increase, Reactive oxygen species
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.15KE:1239Altered, Gene Expression
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular system disease-0.12KE:2001Cardiac hypertrophy
KE:1115Increase, Reactive oxygen species
AOP:453Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general populationGastrointestinal system disease-0.08KE:1115Increase, Reactive oxygen species
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.18KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal system disease-0.08KE:1115Increase, Reactive oxygen species
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.22KE:1825Increase, Cell death
KE:1115Increase, Reactive oxygen species
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.06KE:1115Increase, Reactive oxygen species
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.08KE:1115Increase, Reactive oxygen species

Associated AOPs with Level of Relevance - 5 AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO

AOP Identifier AOP Title AO Classification OECD Status Taxonomic applicability Coverage Score The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints. KE Identifier KE Name
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-Fish0.5KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-Fish0.5KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-Fish0.5KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-Daphnia magna, Daphnia middendorffiana, Daphnia pulex, Daphnia pulicaria, Daphnia parvula0.5KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.6KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.6KE:1821Decrease, Cell proliferation
KE:1521Decrease, Growth
KE:1115Increase, Reactive oxygen species
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.33KE:1817Apoptotic cell death
KE:1115Increase, Reactive oxygen species
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive disorder-Human0.29KE:1115Increase, Reactive oxygen species
KE:402Cognitive function, decreased
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.4KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.4KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.15KE:2216Binding of antagonist to thyroid hormone receptor
KE:341Impairment, Learning and memory

DISCLAIMER

We have built a comprehensive resource which compiles potential endocrine disrupting chemicals (EDCs) based on the observed adverse effects or endocrine-mediated endpoints in published experiments on humans or rodents to support basic research. We are not responsible for any errors or omissions in the published research articles or supporting literature on potential EDCs compiled in this resource. Users are advised to exercise their own judgement on the weight of evidence for potential EDCs compiled in this resource. Importantly, our sole goal to build this resource on potential EDCs is to enable future basic research towards better understanding of the systems-level perturbations upon chemical exposure rather than influencing regulatory advice on chemical use.