alpha-Naphthoflavone


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:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic diseaseWPHA/WNT EndorsedMus musculus, Drosophila melanogaster, Oryzias latipes, Syrian golden hamster0.25KE:155Inadequate DNA repair
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.4KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.14KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-Honey bee0.12KE:664Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular system diseaseUnder DevelopmentHuman, Mouse, Rat, Cow0.1KE:933KE6 : Depletion, Nitric Oxide
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.25KE:1281Increased, DNA Damage-Repair
KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.17KE:1262Apoptosis
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-Lemna minor, Lemna gibba0.09KE:40Decrease, Mitochondrial ATP production
AOP:258Renal protein alkylation leading to kidney toxicityUrinary system diseaseUnder DevelopmentHuman, Rat, Mouse0.2KE:40Decrease, Mitochondrial ATP production
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:155Inadequate DNA repair
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.5KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1771Decrease, Adenosine triphosphate pool
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.5KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-Daphnia magna0.25KE:1771Decrease, Adenosine triphosphate pool
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic disease; Chromosomal diseaseWPHA/WNT EndorsedHuman, Mice, Rat, Fish0.2KE:155Inadequate DNA repair
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.2KE:155Inadequate DNA repair
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-Daphnia magna0.2KE:1769Increase, Body fluid overload
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-Daphnia magna0.2KE:1771Decrease, Adenosine triphosphate pool
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-Daphnia magna, Paracyclopina nana0.2KE:1771Decrease, Adenosine triphosphate pool
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-0.6KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive system disease-Lemna minor0.12KE:40Decrease, Mitochondrial ATP production
AOP:397Bulky DNA adducts leading to mutationsGenetic diseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-Zebrafish0.12KE:1821Decrease, Cell proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.09KE:155Inadequate DNA repair
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular system disease-0.08KE:1919Increased, Cardiac Dysregulation
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: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:155Inadequate DNA repair
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.1KE:18Activation, AhR
KE:1262Apoptosis
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:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.09KE:1262Apoptosis
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE:155Inadequate DNA repair
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular system disease; Thoracic diseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:1183Decreased, Apoptosis (Epithelial Cells)
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 sapiens0.14KE:1262Apoptosis
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.11KE:1262Apoptosis
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.11KE:1262Apoptosis
AOP:564DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.Unclassified-Zebrafish0.09KE:40Decrease, Mitochondrial ATP production

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:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.4KE:716Increase, cell proliferation (hepatocytes)
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal system diseaseUnder ReviewRattus norvegicus, Mus musculus0.4KE:716Increase, cell proliferation (hepatocytes)
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.17KE:719Increase, hepatocellular adenomas and carcinomas
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.5KE:716Increase, cell proliferation (hepatocytes)
KE:719Increase, hepatocellular adenomas and carcinomas
AOP:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.5KE:885Increase, Cancer
KE:155Inadequate DNA repair
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: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, Rat0.2KE: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:885Increase, Cancer
KE:1446Decrease, Coupling of oxidative phosphorylation
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:95Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survivalUnclassified-0.17KE:593Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel
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:151AhR activation leading to preeclampsiaCardiovascular system diseaseUnder DevelopmentHomo sapiens, Mus musculus0.14KE:18Activation, AhR
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.75KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1821Decrease, Cell proliferation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.5KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.33KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.4KE:1821Decrease, Cell proliferation
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.08KE:18Activation, AhR
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:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:18Activation, AhR
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:18Activation, AhR
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.2KE:18Activation, AhR
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.5KE:18Activation, AhR
KE:1262Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:18Activation, AhR
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.56KE:18Activation, AhR
KE:1190Increased, Migration (Endothelial Cells)
KE:1971Increased, tumor growth
KE:1241Increased, Motility
KE:1262Apoptosis
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, Rat0.11KE:18Activation, AhR
AOP:494AhR activation leading to liver fibrosisGastrointestinal system disease-Mus musculus, Homo sapiens0.17KE:18Activation, AhR
AOP:555Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failureCardiovascular system disease-Human and other cells in culture, Dogs, Rat, Guinea pig, Rabbits, Zebrafish0.2KE:593Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel
AOP:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive system disease; Endocrine system disease-Rat, Mouse, Zebra fish, Human0.33KE:18Activation, AhR
KE:1262Apoptosis

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:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Gallus gallus0.4KE:18Activation, AhR
KE:947Increase, Early Life Stage Mortality
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.5KE:719Increase, hepatocellular adenomas and carcinomas
KE:786Increase, Cytotoxicity (hepatocytes)
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT EndorsedChicken, Zebrafish, Mouse, Rattus norvegicus0.29KE:18Activation, AhR
KE:947Increase, Early Life Stage Mortality
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, Chicken0.33KE:18Activation, AhR
KE:947Increase, Early Life Stage Mortality
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder ReviewZebrafish, Mouse, Human, Chicken0.33KE:18Activation, AhR
KE:947Increase, Early Life Stage Mortality

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.