Tolylfluanid


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: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, Zebrafish0.12KE:52Decreased, Calcium influx
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., Rat0.1KE:52Decreased, Calcium influx
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:149Increase, Inflammation
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-Mus musculus, Rattus norvegicus0.2KE:149Increase, Inflammation
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:190Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.17KE:1829Altered, Thyroid hormone-dependent gene expression
AOP:191Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.5KE:1154Increased, Triiodothyronine (T3) in tissues
KE:1829Altered, Thyroid hormone-dependent gene expression
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder DevelopmentHomo sapiens0.17KE:149Increase, Inflammation
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.12KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.17KE:1262Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.2KE:1392Oxidative Stress
AOP:232NFE2/Nrf2 repression to steatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:1419Reduced, FXR activity
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous system disease-Human0.14KE:1392Oxidative Stress
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.2KE:2071Decrease, Glucose pool
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal system disease; Respiratory system disease-0.14KE:149Increase, Inflammation
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1825Increase, Cell death
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:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-Daphnia magna0.25KE:1825Increase, Cell death
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: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:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-Daphnia magna0.2KE:1365Increase, Apoptosis
AOP:362Immune mediated hepatitisGastrointestinal system disease; Immune system disease-Homo sapiens, Rat0.25KE:1817Apoptotic cell death
KE:1633Increase in inflammation
AOP:368Cytochrome oxidase inhibition leading to increased nasal lesionsUnclassified-Rodents, Human0.33KE:1825Increase, Cell death
AOP:388Deposition of ionising energy leading to population decline via programmed cell deathReproductive system disease-Lemna minor0.2KE:1864Increase, Programmed cell death
AOP:410GSK3beta inactivation leading to increased mortality via defects in developing inner earUnclassified-Zebrafish0.1KE:1825Increase, Cell death
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.2KE:1825Increase, Cell death
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.25KE:1262Apoptosis
AOP:431Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Inherited metabolic disorder-Human0.2KE:1952Abnormal, Glucose homeostasis
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:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.22KE:149Increase, Inflammation
KE:1262Apoptosis
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:112Antagonism, Estrogen receptor
AOP:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.22KE:1392Oxidative Stress
KE:1365Increase, Apoptosis
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.15KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.25KE:1392Oxidative Stress
KE:1365Increase, Apoptosis
KE:1633Increase in inflammation
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular system disease-0.06KE:1392Oxidative Stress
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.18KE:1392Oxidative Stress
KE:1262Apoptosis
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:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.11KE:1392Oxidative Stress
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.22KE:2043Decrease, Sonic Hedgehog second messenger production
KE:1262Apoptosis
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.27KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous system disease-0.11KE:1392Oxidative Stress
KE:1825Increase, Cell death
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:2050Increase, developmental abnormalities
AOP:467Knickkopf leading to mortalityUnclassified-0.11KE:2050Increase, developmental abnormalities
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 monkeys0.29KE:1392Oxidative Stress
KE:1825Increase, Cell death
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 DevelopmentMouse0.33KE:2043Decrease, Sonic Hedgehog second messenger production
KE:1262Apoptosis
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: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: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, Rat0.4KE:1392Oxidative Stress
KE:149Increase, Inflammation
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.17KE:1392Oxidative Stress
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular system disease-0.29KE:1392Oxidative Stress
KE:1365Increase, Apoptosis
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.1KE:1392Oxidative Stress
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: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, Human0.22KE:1392Oxidative Stress
KE:1262Apoptosis
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:1392Oxidative Stress
KE:1262Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.08KE:1392Oxidative Stress
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous system disease-Homo sapiens, Mus musculus0.17KE:149Increase, Inflammation
AOP:550Increased LMNA gene mutation leading to heart failureCardiovascular system disease-Human, Mouse, Rat0.2KE:2066Altered Signaling Pathways
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: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:205AOP from chemical insult to cell deathUnclassified-Vertebrates0.17KE:1262Apoptosis
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10013Impaired growth and development
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder DevelopmentHumans0.2KE:1868Hyperinflammation
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1868Hyperinflammation
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.17KE:1817Apoptotic cell death
AOP:457Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxineInherited metabolic disorder-Human0.33KE:1392Oxidative Stress
KE:2119Insulin resistance, increased
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.25KE:1825Increase, Cell death
KE:1868Hyperinflammation
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.3KE:2119Insulin resistance, increased
KE:1633Increase in inflammation
KE:2129Metabolically unhealthy Obesity
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-0.38KE:1392Oxidative Stress
KE:2144Impaired insulin signaling
KE:2119Insulin resistance, increased

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:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:12Acetylcholinesterase (AchE) Inhibition
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:111Decrease in androgen receptor activity leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus0.2KE:1614Decrease, androgen receptor activation
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous system disease-0.1KE:12Acetylcholinesterase (AchE) Inhibition
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderUnder DevelopmentHuman, Mouse0.2KE:1656Antagonism, Thyroid Receptor
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:312Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​Unclassified-0.17KE:12Acetylcholinesterase (AchE) Inhibition
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:405Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive functionCognitive disorder-Rattus norvegicus, Mus musculus, Homo sapiens0.2KE:12Acetylcholinesterase (AchE) Inhibition
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:450Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortalityNervous system disease-Rattus norvegicus, Mus musculus, Homo sapiens0.29KE:1392Oxidative Stress
KE:12Acetylcholinesterase (AchE) Inhibition
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.33KE:1392Oxidative Stress
KE:1825Increase, Cell death
KE:149Increase, Inflammation
AOP:477Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspringPhysical disorder-0.67KE:1614Decrease, androgen receptor activation
KE:26Antagonism, Androgen receptor
AOP:485Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognitionCognitive disorder-Human0.14KE:1656Antagonism, Thyroid Receptor
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:1656Antagonism, Thyroid Receptor
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:36Inhibition, Aromatase
AOP:559Inhibition of acetylcholinesterase (AChE) leading to arrhythmiasSymptom-Human and other cells in culture, Rattus norvegicus, Dogs, Sus scrofa, Zebrafish, Insecta sp. BOLD:AAN51990.2KE:12Acetylcholinesterase (AchE) Inhibition

No associated AOPs with Level of Relevance 5

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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.