Bexarotene


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:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal system diseaseUnder DevelopmentHumans0.25KE:149Increase, Inflammation
KE:288Activation of specific nuclear receptors, Transcriptional change
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-Human, Mouse, Rat0.06KE:454Increased, Triglyceride formation
AOP:107Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the ratCancer; Gastrointestinal system diseaseUnder ReviewRattus norvegicus, Mus musculus0.2KE:1214Altered gene expression specific to CAR activation, Hepatocytes
AOP:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.17KE:111Agonism, Estrogen receptor
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 frog0.25KE:1829Altered, Thyroid hormone-dependent gene expression
AOP:232NFE2/Nrf2 repression to steatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:1419Reduced, FXR activity
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal system disease; Respiratory system disease-0.14KE:149Increase, Inflammation
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.11KE:149Increase, Inflammation
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:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.05KE:149Increase, Inflammation
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.09KE:2009Activation of inflammation pathway
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:149Increase, Inflammation
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748Increased, Estrogen receptor (ER) activity
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.11KE:149Increase, Inflammation
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.17KE:2043Decrease, Sonic Hedgehog second messenger production
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.2KE:149Increase, Inflammation
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.17KE:2009Activation of inflammation pathway
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.1KE:2165Activation of PPAR
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.06KE:2009Activation of inflammation pathway
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.2KE:233Decreased, PPAR-gamma activation
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.08KE:2009Activation of inflammation pathway
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous system disease-Homo sapiens, Mus musculus0.17KE:149Increase, Inflammation

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:313Stimulation of TLR7/8 in dendric cells leading to Psoriatic skin diseaseImmune system disease; Integumentary system disease; Musculoskeletal system diseaseUnder DevelopmentHomo sapiens, Mus musculus0.2KE:1709Psoriatic skin disease

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:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous system diseaseUnder DevelopmentRat0.11KE:239Activation, Pregnane-X receptor, NR1l2
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:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.17KE:454Increased, Triglyceride formation
KE:245Activation, PXR/SXR
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder DevelopmentHomo sapiens0.33KE:1270Inactivation of PPARγ
KE:149Increase, Inflammation
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:347Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosisMusculoskeletal system disease; Respiratory system disease-0.11KE:1270Inactivation of PPARγ
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, Mice0.22KE:1046Suppression, Estrogen receptor (ER) activity
KE:1973Increased, estrogens
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.1KE:2126Estrogen receptor alpha inactivation
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-0.12KE:2126Estrogen receptor alpha inactivation
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.2KE:239Activation, Pregnane-X receptor, NR1l2
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:532Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor functionUnclassified-0.2KE:2201Agonism, Retinoic acid receptor
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:111Agonism, Estrogen receptor
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:111Agonism, Estrogen receptor
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:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:36Inhibition, Aromatase

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.