2,4-Dinitrotoluene


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:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.29KE:520Decreased sperm quantity or quality in the adult, Decreased fertility
KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:96Axonal sodium channel modulation leading to acute mortalityUnclassified-Insects, Fish0.17KE:602Increased, Ataxia, paralysis, or hyperactivity
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:113Glutamate-gated chloride channel activation leading to acute mortalityUnclassified-Bombus impatiens, Chaetanaphothrips orchidii, Radopholus similis, Daphnia magna, Orius insidiosus, Hymenoptera, Helicoverpa zea, Lepidoptera, Liriomyza trifolii, Orius isidiosus, Acyrthosiphon kondoi0.17KE:764N/A, Ataxia, paralysis, or hyperactivity
AOP:120Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)Cancer; Reproductive system disease-Rattus norvegicus, Mus musculus0.2KE:791Increased, Leutinizing hormone (LH)
AOP:194Hepatic nuclear receptor activation leading to altered amphibian metamorphosisUnclassified-African clawed frog0.17KE:295Induction, Upregulation of glucuronyltransferase activity
AOP:323PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-KetotestosteroneUnclassified-Teleost fish0.17KE:1758Impaired, Spermatogenesis
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:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.11KE:1798Decreased spermatogenesis
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.1KE:18Activation, AhR
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.14KE:1758Impaired, Spermatogenesis

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:270Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activityUnclassified-0.12KE:10016Impaired locomotor activity
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.2KE:1757Reduce, Sperm count

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 DevelopmentRat0.22KE:295Induction, Upregulation of glucuronyltransferase activity
KE:239Activation, Pregnane-X receptor, NR1l2
AOP:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:12Acetylcholinesterase (AchE) Inhibition
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Gallus gallus0.2KE:18Activation, AhR
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT EndorsedPimephales promelas0.1KE:25Agonism, Androgen 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:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.25KE:25Agonism, Androgen receptor
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited metabolic disorderWPHA/WNT EndorsedMouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling0.33KE:18Activation, AhR
KE:850Induction, CYP1A2/CYP1A5
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:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.2KE:1391Activation of Cyp2E1
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous system disease-0.1KE:12Acetylcholinesterase (AchE) Inhibition
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.08KE:18Activation, AhR
AOP:312Acetylcholinesterase Inhibition leading to Acute Mortality via Impaired Coordination & Movement​Unclassified-0.17KE:12Acetylcholinesterase (AchE) Inhibition
AOP:376Androgen receptor agonism leading to male-biased sex ratioUnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Fathead minnow, Channel catfish, Oreochromis niloticus, Chinook salmon0.25KE:25Agonism, 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: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-0.25KE:18Activation, AhR
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, Mice0.11KE:18Activation, AhR
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:12Acetylcholinesterase (AchE) Inhibition
KE:1391Activation of Cyp2E1
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, Human0.25KE:18Activation, AhR
KE:295Induction, Upregulation of glucuronyltransferase activity
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.22KE:18Activation, AhR
KE:850Induction, CYP1A2/CYP1A5
AOP:494AhR activation leading to liver fibrosisGastrointestinal system disease-Mus musculus, Homo sapiens0.17KE:18Activation, AhR
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:25Agonism, Androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）Unclassified-Zebrafish0.1KE:25Agonism, Androgen receptor
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.2KE:239Activation, Pregnane-X receptor, NR1l2
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: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
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

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.