Indole-3-carbinol


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:7Aromatase (Cyp19a1) reduction leading to impaired fertility in adult femaleReproductive system disease; Endocrine system disease; Reproductive system diseaseUnder ReviewRat, Mouse, Human0.4KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:15Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutationsGenetic diseaseWPHA/WNT EndorsedMus musculus, Drosophila melanogaster, Oryzias latipes, Syrian golden hamster0.25KE:155Inadequate DNA repair
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT EndorsedPimephales promelas0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:25Aromatase inhibition leading to reproductive dysfunctionUnclassifiedWPHA/WNT EndorsedFathead minnow, Medaka, Zebrafish0.25KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
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:63Cyclooxygenase inhibition leading to reproductive dysfunctionReproductive system disease-Goldfish, Human, Mouse, Rat0.2KE:488Decrease, Ovulation
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.14KE:496Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:80Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failureUnclassified-Honey bee0.12KE:664Overwhelmed, Mitochondrial DNA repair mechanisms
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:112Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)Reproductive system disease; Cancer-Rattus norvegicus0.33KE:111Agonism, Estrogen receptor
KE:749Decreased, Progesterone from corpus luteum
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:122Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formationUnclassified-Pimephales promelas0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:123Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcriptionUnclassified-Pimephales promelas0.18KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.25KE:155Inadequate DNA repair
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular system diseaseUnder DevelopmentHuman, Mouse, Rat, Cow0.1KE:933KE6 : Depletion, Nitric Oxide
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1065Activation, estrogen receptor alpha
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.25KE:1281Increased, DNA Damage-Repair
KE:1262Apoptosis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.17KE:1262Apoptosis
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder DevelopmentFish0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:155Inadequate DNA repair
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1821Decrease, Cell proliferation
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder DevelopmentFish0.17KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.25KE:1821Decrease, Cell proliferation
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic disease; Chromosomal diseaseWPHA/WNT EndorsedHuman, Mice, Rat, Fish0.2KE:155Inadequate DNA repair
AOP:309Luteinizing hormone receptor antagonism leading to reproductive dysfunctionUnclassified-Fish0.43KE:1693Reduction, Plasma progesterone concentration
KE:1692Reduction, Progesterone synthesis
KE:1695Impaired ovulation
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.2KE:155Inadequate DNA repair
AOP:331Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferationUnclassified-Daphnia magna, Daphnia middendorffiana, Daphnia pulex, Daphnia pulicaria, Daphnia parvula0.17KE:1821Decrease, Cell proliferation
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.2KE:1821Decrease, Cell proliferation
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.4KE:1821Decrease, Cell proliferation
KE:1446Decrease, Coupling of oxidative phosphorylation
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:1789Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:397Bulky DNA adducts leading to mutationsGenetic diseaseUnder Development0.33KE:155Inadequate DNA repair
AOP:399Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)Unclassified-Zebrafish0.12KE:1821Decrease, Cell proliferation
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.09KE:155Inadequate DNA repair
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:1973Increased, estrogens
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 norvegicus0.29KE:1974Activation of Tumor Protein 53
KE: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:155Inadequate DNA repair
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.15KE:18Activation, AhR
KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:1262Apoptosis
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.09KE:1262Apoptosis
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.22KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:465Alcohol dehydrogenase leading to reproductive dysfunctionUnclassified-0.12KE:748Increased, Estrogen receptor (ER) activity
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.1KE:155Inadequate DNA repair
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:1183Decreased, Apoptosis (Epithelial Cells)
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.1KE:219Reduction, Plasma 17beta-estradiol concentrations
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:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.17KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.11KE:1262Apoptosis
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
KE:1262Apoptosis
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:219Reduction, Plasma 17beta-estradiol concentrations

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:205AOP from chemical insult to cell deathUnclassified-Vertebrates0.17KE:1262Apoptosis
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.2KE:1395Liver Cancer
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:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.18KE:2034liver dysfunction
KE:1262Apoptosis
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.12KE:1868Hyperinflammation
AOP:504SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ levelUnclassified-Mammals0.33KE:1065Activation, estrogen receptor alpha
AOP:561Aromatase induction leading to estrogen receptor alpha activation via increased estradiolUnclassified-Vertebrates0.2KE:1065Activation, estrogen receptor alpha

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 DevelopmentRat0.11KE:239Activation, Pregnane-X receptor, NR1l2
AOP:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Gallus gallus0.2KE:18Activation, AhR
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.4KE:165Activation, Long term AHR receptor driven direct and indirect gene expression changes
KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.08KE:245Activation, PXR/SXR
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited metabolic disorderWPHA/WNT EndorsedMouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling0.17KE:18Activation, AhR
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: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:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.5KE:1821Decrease, Cell proliferation
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:265Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calciumUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:266Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activityUnclassifiedUnder Development0.17KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:267Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletionUnclassifiedUnder Development0.4KE:1821Decrease, Cell proliferation
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:268Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swellingUnclassifiedUnder Development0.25KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:269Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and developmentUnclassified-0.17KE:10008Increased transcription for detoxification and repair mechanism
AOP:270Elevated ATP demand for detoxification and repair mechanisms leading to impaired locomotor activityUnclassified-0.12KE:10008Increased transcription for detoxification and repair mechanism
AOP:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.25KE:18Activation, AhR
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
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-0.4KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.4KE:18Activation, AhR
KE:17Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.75KE:18Activation, AhR
KE:1923Altered gene expression, P53 dependent apoptosis pathway
KE:1262Apoptosis
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, Mice0.22KE:18Activation, AhR
KE:1262Apoptosis
AOP:445Estrogen Receptor Alpha Agonism leads to Impaired ReproductionReproductive system disease-0.25KE:1065Activation, estrogen receptor alpha
KE:1989Impaired, Oocyte maturation and ovulation
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, Human0.12KE:18Activation, AhR
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.11KE:18Activation, AhR
AOP:494AhR activation leading to liver fibrosisGastrointestinal system disease-Mus musculus, Homo sapiens0.17KE:18Activation, AhR
AOP:503Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulationReproductive system disease; CancerUnder ReviewHuman, Mouse0.17KE:1065Activation, estrogen receptor alpha
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.2KE:239Activation, Pregnane-X receptor, NR1l2
AOP:525Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.15KE:2217Binding of antagonist to glucocorticoid hormone receptor
KE:2220Antagonism, Glucocorticoid hormone 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:563Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosisReproductive system disease; Endocrine system disease-Rat, Mouse, Zebra fish, Human0.33KE:18Activation, AhR
KE:1262Apoptosis

No associated AOPs with Level of Relevance 5

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