FD&C Red 3


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:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.4KE:854Alterations, Cellular proliferation / hyperplasia
KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:975-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population declineUnclassified-Mytilus galloprovincialis, Tritonea diomedea, Lymnaea stagnalis, Melibe leonine, Helix lucorum, Lampsilis fasciola0.1KE:626Increased, serotonin (5-HT)
AOP:985-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to decreased shelter seeking and increased predationUnclassified-Pimephales promelas, Echinogammarus marinus0.2KE:626Increased, serotonin (5-HT)
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:1023Increased, Thyroid-stimulating hormone (TSH)
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:1023Increased, Thyroid-stimulating hormone (TSH)
AOP:155Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedFathead minnow, Zebrafish0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:156Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:157Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:158Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.17KE:1003Decreased, Triiodothyronine (T3)
AOP:159Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflationUnclassifiedWPHA/WNT EndorsedZebrafish, Fathead minnow0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:189Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.5KE:1116Decreased, Triiodothyronine (T3) in tissues
KE:1003Decreased, Triiodothyronine (T3)
AOP:190Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosisUnclassified-African clawed frog0.5KE:1116Decreased, Triiodothyronine (T3) in tissues
KE:1829Altered, Thyroid hormone-dependent gene expression
KE:1023Increased, Thyroid-stimulating hormone (TSH)
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:1955-hydroxytryptamine transporter (5-HTT) inhibition leading to population increaseUnclassified-Argopecten irradians, Mercenaria mercenaria, Arctica islandica, Spisula solidissima, Anodonta cygnea, Dreissena polymorpha0.12KE:626Increased, serotonin (5-HT)
AOP:2035-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population declineReproductive system disease-0.12KE:626Increased, serotonin (5-HT)
AOP:2045-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increaseUnclassified-0.12KE:626Increased, serotonin (5-HT)
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder DevelopmentHomo sapiens0.17KE:1271Activation of TGF-β signaling
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.4KE:1393Hepatocytotoxicity
KE:1394Induction, persistent proliferation/sustained proliferation
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:1636Increase, Chromosomal aberrations
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:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.2KE:1614Decrease, androgen receptor activation
AOP:321Reduced environmental pH leading to thinner shells in Mytilus edulisUnclassified-0.09KE:10039Higher antioxidant enzyme activities and lipid peroxidation
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-Daphnia magna0.2KE:1769Increase, Body fluid overload
AOP:347Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosisMusculoskeletal system disease; Respiratory system disease-0.22KE:1795Latent Transforming growth Factor beta expression
KE:1283Activation, TGF-beta pathway
AOP:363Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structureUnclassifiedUnder ReviewZebrafish0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:364Thyroperoxidase inhibition leading to altered visual function via decreased eye sizeUnclassifiedUnder Development0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:365Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterningUnclassifiedUnder Development0.12KE:1003Decreased, Triiodothyronine (T3)
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular system diseaseUnder DevelopmentHomo sapiens0.14KE:1869Diminished protective oxidative stress response
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1869Diminished protective oxidative stress response
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal system disease; Respiratory system disease-0.2KE:1920Altered gene expression, TGF-β dependent fibrosis pathway
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.25KE:1923Altered gene expression, P53 dependent apoptosis pathway
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.11KE:1971Increased, tumor growth
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, Yeast0.1KE:1554Increase Chromosomal Aberrations
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE:1636Increase, Chromosomal aberrations
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive disorder-Human0.14KE:1869Diminished protective oxidative stress response
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:854Alterations, Cellular proliferation / hyperplasia
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.06KE:2171Activated BMP/TGF-beta pathway
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.08KE:1656Antagonism, Thyroid Receptor
AOP:568Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, FeedingUnclassified-Fish0.25KE:1320Increased, extracellular serotonin

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:124HMG-CoA reductase inhibition leading to decreased fertilityReproductive system disease-Rattus rattus0.17KE:330Decrease, Fertility
AOP:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.25KE:885Increase, Cancer
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic disease; Chromosomal diseaseWPHA/WNT EndorsedHuman, Mice, Rat, Fish0.2KE:1636Increase, Chromosomal aberrations
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary system disease-0.17KE:1603Chronic kidney disease
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:2092Promotion, Ovarian Cancer
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE:885Increase, Cancer
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:2150Neurological disorder
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-Vertebrates0.17KE: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:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:12Acetylcholinesterase (AchE) Inhibition
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:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.25KE:786Increase, Cytotoxicity (hepatocytes)
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.12KE:1286Down Regulation, GSS and GSTs gene
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:241Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosisMusculoskeletal system disease; Respiratory system disease-0.33KE:1468Activation, Latent Transforming Growth Factor Beta 1
KE:1469Activation, Transforming Growth Factor beta pathway
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous system disease-0.1KE:12Acetylcholinesterase (AchE) Inhibition
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal system diseaseUnder ReviewHomo sapiens0.17KE:1753Chronic reactive oxygen species
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, Mouse0.5KE: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 Development0.5KE: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:405Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive functionCognitive disorder-Rattus norvegicus, Mus musculus, Homo sapiens0.2KE:12Acetylcholinesterase (AchE) Inhibition
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:12Acetylcholinesterase (AchE) Inhibition
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: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

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:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.4KE:337N/A, Impairment of reproductive capacity
KE:26Antagonism, Androgen receptor

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.