Triflumizol


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:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal system diseaseUnder DevelopmentHumans0.12KE:288Activation of specific nuclear receptors, Transcriptional change
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderWPHA/WNT EndorsedHuman, Rat, Mouse0.12KE:277Thyroid hormone synthesis, Decreased
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental disorder of mental healthWPHA/WNT EndorsedHomo sapiens, Rattus sp.0.1KE:277Thyroid hormone synthesis, Decreased
AOP:62AKT2 activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.25KE:457Activation, SREBF1
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:726Increased, Induction of pyruvate dehydrogenase (PDH)
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:277Thyroid hormone synthesis, Decreased
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:749Decreased, Progesterone from corpus luteum
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:277Thyroid hormone synthesis, Decreased
AOP:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-Pimephales promelas0.1KE:800Decreased, Aromatase (Cyp19a1) mRNA
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-Pimephales promelas0.09KE:800Decreased, Aromatase (Cyp19a1) mRNA
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited metabolic disorderWPHA/WNT EndorsedMouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling0.17KE:850Induction, CYP1A2/CYP1A5
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Homo sapiens0.11KE:277Thyroid hormone synthesis, Decreased
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.12KE:277Thyroid hormone synthesis, Decreased
AOP:175Thyroperoxidase inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.25KE:277Thyroid hormone synthesis, Decreased
AOP:176Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.2KE:277Thyroid hormone synthesis, Decreased
AOP:192Pendrin inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.25KE:277Thyroid hormone synthesis, Decreased
AOP:193Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.25KE:277Thyroid hormone synthesis, Decreased
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.12KE:1289Perturbation of cholesterol
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:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder DevelopmentFish0.2KE:277Thyroid hormone synthesis, Decreased
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.4KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
AOP:309Luteinizing hormone receptor antagonism leading to reproductive dysfunctionUnclassified-Fish0.29KE:1693Reduction, Plasma progesterone concentration
KE:1692Reduction, Progesterone synthesis
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.09KE:10042Abnormal development
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder ReviewZebrafish0.12KE:277Thyroid hormone synthesis, Decreased
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:277Thyroid hormone synthesis, Decreased
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:277Thyroid hormone synthesis, Decreased
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:1917Altered gene expression, NRF2 dependent antioxidant pathway
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: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:112Antagonism, Estrogen receptor
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1392Oxidative Stress
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive system disease-0.12KE:1987Decreased, Androgen and Progestin
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.05KE:1392Oxidative Stress
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-Human0.33KE:1392Oxidative Stress
KE:277Thyroid hormone synthesis, Decreased
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.33KE:1392Oxidative Stress
KE:277Thyroid hormone synthesis, Decreased
KE:850Induction, CYP1A2/CYP1A5
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.11KE:2043Decrease, Sonic Hedgehog second messenger production
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: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:2043Decrease, Sonic Hedgehog second messenger production
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:286Altered, Transcription of genes by the androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.1KE:286Altered, Transcription of genes by the androgen receptor
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:1392Oxidative Stress
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.2KE: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:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.2KE:233Decreased, PPAR-gamma activation
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.14KE:1392Oxidative Stress
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.17KE: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:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development

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:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive system disease; Endocrine system disease; Reproductive system diseaseUnder ReviewRat, Mouse, Human0.2KE:408reduction in ovarian granulosa cells, Aromatase (Cyp19a1)
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.25KE:227Activation, PPARα
KE:289Decrease, Translocator protein (TSPO)
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.4KE:286Altered, Transcription of genes by the androgen receptor
KE:26Antagonism, Androgen receptor
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT EndorsedFathead minnow, Medaka, Zebrafish0.12KE:36Inhibition, Aromatase
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder ReviewZebra danio, Fathead minnow, Medaka0.17KE:112Antagonism, Estrogen receptor
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:233Decreased, PPAR-gamma activation
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.2KE:227Activation, PPARα
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-Human, Mouse, Rat0.12KE:456Suppression, Constitutive androstane receptor, NR1l3
KE:457Activation, SREBF1
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:128Kidney dysfunction by decreased thyroid hormoneUrinary system diseaseUnder DevelopmentSprague-Dawley, Homo sapiens0.09KE:277Thyroid hormone synthesis, Decreased
AOP:155Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedFathead minnow, Zebrafish0.17KE:1002Inhibition, Deiodinase 2
AOP:156Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1002Inhibition, Deiodinase 2
AOP:188Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.4KE:277Thyroid hormone synthesis, Decreased
KE:1152Inhibition, Iodotyrosine deiodinase (IYD)
AOP:190Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.17KE:1002Inhibition, Deiodinase 2
AOP:191Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.25KE:1153Inhibition, Deiodinase 3
AOP:232NFE2/Nrf2 repression to steatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:1417NFE2/Nrf2 repression
AOP:233Mu Opioid Receptor Agonism leading to Analgesia via K Channel OpeningDevelopmental disorder of mental health-0.2KE:1425Mu Opioid Receptor Agonism
AOP:234Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel InhibitionDevelopmental disorder of mental health-0.2KE:1425Mu Opioid Receptor Agonism
AOP:288Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)Endocrine system disease-Human, Rat0.25KE:1609Inhibition, Cytochrome P450 enzyme (CYP17A1) activity
KE:1614Decrease, androgen receptor activation
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.75KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-Teleost fish0.17KE:227Activation, PPARα
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.75KE:286Altered, Transcription of genes by the androgen receptor
KE: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 DevelopmentMammals0.5KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:346Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiationUnclassifiedWPHA/WNT EndorsedZebrafish, Oreochromis niloticus, Chinook salmon, Fathead minnow, European sea bass0.2KE:36Inhibition, Aromatase
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine system disease; Reproductive system disease; Cancer-0.6KE:286Altered, Transcription of genes by the androgen receptor
KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory system disease-Homo sapiens0.25KE:1392Oxidative Stress
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: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: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: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:520Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-Mouse, Rat, Human0.2KE:2201Agonism, Retinoic acid receptor
AOP:523Retinoic acid receptor agonism during neurodevelopment leading to microcephalyCongenital nervous system abnormality; Nervous system disease-0.2KE:2201Agonism, Retinoic acid receptor
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.23KE:2217Binding of antagonist to glucocorticoid hormone receptor
KE:2115Altered, cholesterol metabolism
KE:2220Antagonism, Glucocorticoid hormone receptor
AOP:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2201Agonism, Retinoic acid receptor
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.17KE:2232Antagonism, Retinoic acid receptors
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:36Inhibition, Aromatase

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:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.2KE:2126Estrogen receptor alpha inactivation
KE:2129Metabolically unhealthy Obesity

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.