Benzo(k)fluoranthene


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: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:1392Oxidative Stress
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:1214Altered gene expression specific to CAR activation, Hepatocytes
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:111Agonism, Estrogen receptor
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-Pimephales promelas0.1KE:799Increased, HIF-1 heterodimer
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.12KE:1280Activation, HIF-1
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.2KE:1392Oxidative Stress
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous system disease-Human0.14KE:1392Oxidative Stress
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.25KE:1821Decrease, Cell proliferation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.2KE:1821Decrease, Cell proliferation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1821Decrease, Cell proliferation
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:1614Decrease, androgen receptor activation
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.25KE:1821Decrease, Cell proliferation
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.2KE:1614Decrease, androgen receptor activation
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 parvula0.17KE:1821Decrease, Cell proliferation
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1821Decrease, Cell proliferation
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.2KE:1821Decrease, Cell proliferation
AOP:347Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosisMusculoskeletal system disease; Respiratory system disease-0.11KE:1793Activator protein 1 activation
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder Development0.17KE:1172Increased activation, Nuclear factor kappa B (NF-kB)
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-Zebrafish0.12KE:1821Decrease, Cell proliferation
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary system diseaseUnder Development0.2KE:1392Oxidative Stress
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular system disease-0.08KE:1392Oxidative Stress
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:1974Activation of Tumor Protein 53
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic disease; CancerUnder DevelopmentHuman and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast0.3KE:112Antagonism, Estrogen receptor
KE:1554Increase Chromosomal Aberrations
KE:1172Increased activation, Nuclear factor kappa B (NF-kB)
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1392Oxidative Stress
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.15KE:1392Oxidative Stress
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:18Activation, AhR
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular system disease-0.06KE:1392Oxidative Stress
AOP:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous system disease-Rattus norvegicus, Mus musculus, Homo sapiens0.14KE:1392Oxidative Stress
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.09KE: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-0.08KE:1392Oxidative Stress
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited metabolic disorder-Human0.17KE:1392Oxidative Stress
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.11KE:1821Decrease, Cell proliferation
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.09KE:1392Oxidative Stress
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous system disease-0.05KE:1392Oxidative Stress
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748Increased, Estrogen receptor (ER) activity
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal system disease-0.08KE:1392Oxidative Stress
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular system diseaseUnder ReviewHuman, Rat, Mouse, Rabbit0.12KE:1392Oxidative Stress
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE: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:482Deposition of energy leading to occurrence of bone lossMusculoskeletal system diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys0.14KE:1392Oxidative Stress
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental disorder of mental healthUnder ReviewMouse, Rat, Rabbit, Dog, Pigs, Cow, Human0.12KE:1392Oxidative Stress
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive disorder-Human0.14KE:1392Oxidative Stress
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.17KE:1821Decrease, Cell proliferation
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:1392Oxidative Stress
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.2KE:1392Oxidative Stress
KE:2165Activation of PPAR
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.06KE:1392Oxidative Stress
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.14KE:1392Oxidative Stress
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.11KE:1392Oxidative Stress
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.11KE:1392Oxidative Stress
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.08KE:1392Oxidative Stress

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:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.25KE:885Increase, Cancer
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:1556Increase, lung cancer
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder DevelopmentMammals0.14KE:1670Lung cancer
AOP:304TBX1 inhibition leading to congenital cardiac conotruncal anomaliesCardiovascular system disease-0.17KE:1685Anomalies, Congenital cardiac conotruncal
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.11KE:1670Lung cancer
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE:885Increase, Cancer
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.4KE:1392Oxidative Stress
KE:885Increase, Cancer
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.2KE:885Increase, Cancer
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.33KE:1392Oxidative Stress
KE:885Increase, Cancer
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:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous system diseaseUnder DevelopmentRat0.11KE:239Activation, Pregnane-X receptor, NR1l2
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.2KE:26Antagonism, Androgen receptor
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Gallus gallus0.2KE:18Activation, AhR
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder ReviewZebra danio, Fathead minnow, Medaka0.17KE:112Antagonism, Estrogen receptor
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.2KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.14KE:494Glucocorticoid Receptor Agonist, Activation
AOP:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus0.2KE:1614Decrease, androgen receptor activation
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-Pimephales promelas0.27KE:801modulation, Unknown
KE:802Increased, HIF-1 alpha transcription
KE:799Increased, HIF-1 heterodimer
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited metabolic disorderWPHA/WNT EndorsedMouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling0.17KE:18Activation, AhR
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT EndorsedChicken, Zebrafish, Mouse, Rattus norvegicus0.14KE:18Activation, AhR
AOP:151AhR activation leading to preeclampsiaCardiovascular system diseaseUnder DevelopmentHomo sapiens, Mus musculus0.14KE:18Activation, AhR
AOP:232NFE2/Nrf2 repression to steatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:1417NFE2/Nrf2 repression
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.5KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.08KE:18Activation, AhR
AOP:318Glucocorticoid Receptor activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.2KE:122Activation, Glucocorticoid Receptor
AOP:334Glucocorticoid Receptor Agonism Leading to Impaired Fin RegenerationUnclassified-Teleost fish0.17KE:122Activation, Glucocorticoid Receptor
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.5KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine system disease; Reproductive system disease; Reproductive system diseaseUnder DevelopmentMammals0.33KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine system disease; Reproductive system disease; Cancer-0.4KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory system disease-Homo sapiens0.25KE:1392Oxidative Stress
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:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.4KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.5KE:18Activation, AhR
KE:1923Altered gene expression, P53 dependent apoptosis pathway
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory system disease-Human0.17KE:1392Oxidative Stress
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory system disease-Human0.17KE:1392Oxidative Stress
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.22KE:18Activation, AhR
KE:1971Increased, tumor growth
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 DevelopmentHuman, Rat, Mice0.11KE:1046Suppression, Estrogen receptor (ER) activity
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.17KE:1392Oxidative Stress
KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
AOP:455Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced impeded craniofacial developmentMusculoskeletal system diseaseUnder ReviewZebrafish, Mouse, Human, Sebastiscus marmoratus, Salmo salar, Chicken0.17KE:18Activation, AhR
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder ReviewZebrafish, Mouse, Human, Chicken0.17KE:18Activation, AhR
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Mouse, Monkey, Human0.12KE:18Activation, AhR
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.22KE:18Activation, AhR
KE:1392Oxidative Stress
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.11KE: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:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.1KE:2126Estrogen receptor alpha inactivation
AOP:494AhR activation leading to liver fibrosisGastrointestinal system disease-Mus musculus, Homo sapiens0.17KE:18Activation, AhR
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-0.25KE:1392Oxidative Stress
KE:2126Estrogen receptor alpha inactivation
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.33KE:1392Oxidative Stress
KE:1417NFE2/Nrf2 repression
AOP:508Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.14KE:1417NFE2/Nrf2 repression
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular system disease-0.29KE:1392Oxidative Stress
KE:1417NFE2/Nrf2 repression
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.2KE:239Activation, Pregnane-X receptor, NR1l2
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:111Agonism, Estrogen receptor
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:111Agonism, Estrogen receptor
AOP:545Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased cholesterol synthesisUnclassified-Mammals0.2KE:239Activation, Pregnane-X receptor, NR1l2
AOP:548Activation, Pregnane-X receptor, NR1l2 leads to increased plasma low-density lipoprotein (LDL) cholesterol via increased PCSK9 protein expressionUnclassified-Mammals0.2KE:239Activation, Pregnane-X receptor, NR1l2
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:18Activation, AhR

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:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.33KE:18Activation, AhR
KE:1670Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.6KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
KE:1670Lung cancer
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.75KE:18Activation, AhR
KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
KE:1670Lung cancer

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.