Silica


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: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:16Acetylcholinesterase inhibition leading to acute mortalityUnclassifiedUnder Development0.14KE:445Respiratory distress/arrest
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, Human0.2KE:1493Increased Pro-inflammatory mediators
KE:1392Oxidative Stress
AOP:19Androgen receptor antagonism leading to adverse effects in the male foetus (mammals)Reproductive system disease-0.2KE:286Altered, Transcription of genes by the androgen receptor
AOP:27Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)Gastrointestinal system diseaseUnder DevelopmentHumans0.25KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
AOP:37PPARα activation leading to hepatocellular adenomas and carcinomas in rodentsCancer; Gastrointestinal system diseaseUnder DevelopmentMouse, Rat0.2KE:716Increase, cell proliferation (hepatocytes)
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal system diseaseWPHA/WNT EndorsedHuman, Rat0.43KE:1493Increased Pro-inflammatory mediators
KE:68Accumulation, Collagen
KE:265Activation, Stellate cells
AOP:39Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity ResponseRespiratory system diseaseUnder DevelopmentHuman, Mouse0.4KE:272Activation/Proliferation, T-cells
KE:1496Increased, secretion of proinflammatory mediators
AOP:40Covalent Protein binding leading to Skin SensitisationIntegumentary system diseaseWPHA/WNT EndorsedMouse, Human0.4KE:272Activation/Proliferation, T-cells
KE:826Activation, Keratinocytes
AOP:41Sustained AhR Activation leading to Rodent Liver TumoursCancer; Gastrointestinal system diseaseUnder ReviewRattus sp. ABTC 42503, Mus sp. 20000820.6KE:854Alterations, Cellular proliferation / hyperplasia
KE:853Changes/Inhibition, Cellular Homeostasis and Apoptosis
KE:139N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:48Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.Developmental disorder of mental healthWPHA/WNT EndorsedHuman, Mouse, Rat0.11KE:352N/A, Neurodegeneration
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:73Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundityUnclassified-0.08KE:536Altered, Chromosome number (polyploid) zygote
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:94Sodium channel inhibition leading to congenital malformationsUnclassified-Human, Rat, Mouse0.17KE:445Respiratory distress/arrest
AOP:105Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.17KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
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:716Increase, cell proliferation (hepatocytes)
AOP:108Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.17KE:768Increase, Cytotoxicity
AOP:109Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)Cancer; Respiratory system disease-Mus musculus0.2KE:734Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
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:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-Rattus norvegicus0.33KE:778Increase, Regenerative cell proliferation (corneal cells)
KE:777Increase, Inflammation (corneal cells)
AOP:115Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)Cancer-Mus musculus, Rattus norvegicus0.4KE:149Increase, Inflammation
KE:781Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)Cancer; Urinary system disease-Rattus norvegicus0.25KE:710Increase, Regenerative cell proliferation (tubular epithelial cells)
AOP:117Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system diseaseUnder DevelopmentMus musculus, Rattus norvegicus0.25KE:716Increase, cell proliferation (hepatocytes)
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:739Increase, Hypertrophy and proliferation (follicular cell)
AOP:121Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)Cancer; Urinary system disease-Mus musculus, Rattus norvegicus0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:126Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulationUnclassified-0.08KE:536Altered, Chromosome number (polyploid) zygote
AOP:136Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal TumorsBenign neoplasm; Respiratory system diseaseUnder Review0.29KE:768Increase, Cytotoxicity
KE:870Increase, Cell Proliferation
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal system diseaseUnder ReviewHuman, Mouse, Rat0.33KE:1493Increased Pro-inflammatory mediators
KE:68Accumulation, Collagen
KE:265Activation, Stellate cells
AOP:164Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouseCancer; Reproductive system disease-CD-1 mouse, SD rat0.17KE:1042Proliferation/Clonal Expansion, smooth muscle
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1067Proliferation/Clonal Expansion, aberrant basal cells
AOP:207NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegansReproductive system disease-Caenorhabditis elegans0.38KE:1115Increase, Reactive oxygen species
KE:1281Increased, DNA Damage-Repair
KE:1262Apoptosis
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.12KE:1287Glutathione synthesis
AOP:212Histone deacetylase inhibition leading to testicular atrophyReproductive system diseaseWPHA/WNT EndorsedRat, Human, Mouse0.17KE:1262Apoptosis
AOP:213Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)Gastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.17KE:1115Increase, Reactive oxygen species
AOP:220Cyp2E1 Activation Leading to Liver CancerCancer; Gastrointestinal system diseaseWPHA/WNT EndorsedRodents, Homo sapiens0.6KE:1392Oxidative Stress
KE:1393Hepatocytotoxicity
KE:1394Induction, persistent proliferation/sustained proliferation
AOP:228NSAID induced PTGS2 inactivation to gastric ulcerGastrointestinal system disease-0.2KE:1411Increased, leukocyte activation
AOP:237Substance interaction with lung resident cell membrane components leading to atherosclerosisCardiovascular system diseaseUnder DevelopmentHuman, Mouse0.2KE:1496Increased, secretion of proinflammatory mediators
AOP:245Reduction in photophosphorylation leading to growth inhibition in aquatic plantsUnclassified-Lemna minor, Lemna gibba0.09KE:40Decrease, Mitochondrial ATP production
AOP:258Renal protein alkylation leading to kidney toxicityUrinary system diseaseUnder DevelopmentHuman, Rat, Mouse0.2KE:40Decrease, Mitochondrial ATP production
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal system disease; Respiratory system disease-0.14KE:149Increase, Inflammation
AOP:286Mitochondrial complex III antagonism leading to growth inhibition (1)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.5KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
AOP:287Mitochondrial complex III antagonism leading to growth inhibition (2)Unclassified-Lemna minor, Daphnia magna, Danio rerio0.25KE:1771Decrease, Adenosine triphosphate pool
AOP:290Mitochondrial ATP synthase antagonism leading to growth inhibition (1)Unclassified-Daphnia magna0.5KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
AOP:291Mitochondrial ATP synthase antagonism leading to growth inhibition (2)Unclassified-Daphnia magna0.25KE:1771Decrease, Adenosine triphosphate pool
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder DevelopmentRattus rattus, Mus musculus0.22KE:1493Increased Pro-inflammatory mediators
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder Development0.22KE:1493Increased Pro-inflammatory mediators
KE:1182Increase, Cell Proliferation (Epithelial Cells)
AOP:299Deposition of energy leading to population decline via DNA oxidation and follicular atresiaUnclassified-0.14KE:1115Increase, Reactive oxygen species
AOP:3055α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.2KE:286Altered, Transcription of genes by the androgen receptor
AOP:306Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspringUnclassifiedUnder DevelopmentRat, Human, Mouse0.25KE:286Altered, Transcription of genes by the androgen receptor
AOP:311Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosisUnclassified-Daphnia magna, Fish0.14KE:1115Increase, Reactive oxygen species
AOP:320Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortalityUnclassifiedUnder DevelopmentHomo sapiens0.11KE:1496Increased, secretion of proinflammatory mediators
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.4KE:155Inadequate DNA repair
KE:1365Increase, Apoptosis
AOP:335AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairmentCancer; Urinary system disease-Rat0.2KE:795Increase, Regenerative cell proliferation (urothelial cells)
AOP:344Androgen receptor (AR) antagonism leading to nipple retention (NR) in male (mammalian) offspringUnclassifiedUnder Development0.25KE:286Altered, Transcription of genes by the androgen receptor
AOP:345Androgen receptor (AR) antagonism leading to decreased fertility in femalesEndocrine system disease; Reproductive system disease; Reproductive system diseaseUnder DevelopmentMammals0.17KE:286Altered, Transcription of genes by the androgen receptor
AOP:362Immune mediated hepatitisGastrointestinal system disease; Immune system disease-Homo sapiens, Rat0.25KE:1818Immune cell activation
KE:1633Increase in inflammation
AOP:372Androgen receptor antagonism leading to testicular cancerEndocrine system disease; Reproductive system disease; Cancer-0.2KE:286Altered, Transcription of genes by the androgen receptor
AOP:374Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitisNervous system diseaseUnder DevelopmentHuman0.25KE:352N/A, Neurodegeneration
AOP:383Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosisGastrointestinal system diseaseUnder Development0.17KE:1115Increase, Reactive oxygen species
AOP:384Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney diseaseUrinary system disease-0.17KE:1115Increase, Reactive oxygen species
AOP:386Deposition of ionizing energy leading to population decline via inhibition of photosynthesisReproductive system disease-Lemna minor, Chlamydomonas reinhardtii0.12KE:1115Increase, Reactive oxygen species
AOP:387Deposition of ionising energy leading to population decline via mitochondrial dysfunctionReproductive system disease-Lemna minor0.25KE:1115Increase, Reactive oxygen species
KE:40Decrease, Mitochondrial ATP production
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:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.62KE:1115Increase, Reactive oxygen species
KE:870Increase, Cell Proliferation
KE:1496Increased, secretion of proinflammatory mediators
KE:1669Increased, DNA damage and mutation
KE:1497Increased, recruitment of inflammatory cells
AOP:413Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failureUnclassified-Fish, Mice0.33KE:1607Increase, Necrosis
KE:1115Increase, Reactive oxygen species
AOP:431Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)Inherited metabolic disorder-Human0.2KE:1952Abnormal, Glucose homeostasis
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.27KE:1493Increased Pro-inflammatory mediators
KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
AOP:437Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicityUrinary system diseaseUnder Development0.2KE: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:444Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchabilityUnclassified-0.22KE:1392Oxidative Stress
KE:1365Increase, Apoptosis
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: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:352N/A, Neurodegeneration
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:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:464Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficitsNervous system disease-0.05KE:1392Oxidative Stress
AOP:478Deposition of energy leading to occurrence of cataractsNervous system disease; Monogenic diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig0.4KE:1392Oxidative Stress
KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
KE:1636Increase, Chromosomal aberrations
AOP:479Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stressCardiovascular system disease; Thoracic diseaseUnder Development0.14KE:1392Oxidative Stress
AOP:480Mitochondrial complexes inhibition leading to heart failure via decreased ATP productionCardiovascular system disease; Thoracic diseaseUnder Development0.2KE:40Decrease, Mitochondrial ATP production
AOP:482Deposition of energy leading to occurrence of bone lossMusculoskeletal system diseaseUnder ReviewHuman, Mouse, Rat, Rhesus monkeys0.14KE:1392Oxidative Stress
AOP:483Deposition of Energy Leading to Learning and Memory ImpairmentDevelopmental disorder of mental healthUnder ReviewMouse, Rat, Rabbit, Dog, Pigs, Cow, Human0.25KE:1392Oxidative Stress
KE:2244Altered Stress Response Signaling
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.33KE:1821Decrease, Cell proliferation
KE:1262Apoptosis
AOP:492Glutathione conjugation leading to reproductive dysfunction via oxidative stressReproductive system disease-Mammals, Fish0.2KE:1115Increase, Reactive oxygen species
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:1497Increased, recruitment of inflammatory cells
AOP:494AhR activation leading to liver fibrosisGastrointestinal system disease-Mus musculus, Homo sapiens0.17KE:265Activation, Stellate cells
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.33KE:854Alterations, Cellular proliferation / hyperplasia
KE:286Altered, Transcription of genes by the androgen receptor
KE:1183Decreased, Apoptosis (Epithelial Cells)
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.1KE:286Altered, Transcription of genes by the androgen receptor
AOP:498Increased LCN2/iron complex leading to neurological disordersNervous system disease-Homo sapiens0.25KE:191Neuronal dysfunction
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 sapiens0.43KE:1115Increase, Reactive oxygen species
KE:352N/A, Neurodegeneration
KE:1262Apoptosis
AOP:501Excessive iron accumulation leading to neurological disordersNervous system disease-Homo sapiens0.25KE:1392Oxidative Stress
AOP:510Demethylation of PPAR promotor leading to vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.1KE:1392Oxidative Stress
AOP:521Essential element imbalance leads to reproductive failure via oxidative stressUnclassified-Murinae gen. sp.0.29KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:535Binding and activation of GPER leading to learning and memory impairmentsDevelopmental disorder of mental health-Mouse, Human0.22KE:1392Oxidative Stress
KE:1262Apoptosis
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:564DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.Unclassified-Zebrafish0.09KE:40Decrease, Mitochondrial ATP production
AOP:569Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathwayDevelopmental disorder of mental health-0.33KE:1115Increase, Reactive oxygen species
KE:2195Increase, CNS Neural 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: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:352N/A, Neurodegeneration
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 musculus0.5KE:885Increase, Cancer
KE:155Inadequate DNA repair
AOP:148EGFR Activation Leading to Decreased Lung FunctionRespiratory system diseaseUnder DevelopmentHuman, Mouse, Rat0.25KE:1250Decrease, Lung function
AOP:149Peptide Oxidation Leading to HypertensionCardiovascular system diseaseUnder DevelopmentHuman, Mouse, Rat, Cow0.1KE:952Hypertension
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal system disease; Respiratory system diseaseWPHA/WNT EndorsedHuman, Mouse, Rat0.5KE:68Accumulation, Collagen
KE:1497Increased, recruitment of inflammatory cells
KE:1496Increased, secretion of proinflammatory mediators
KE:1458Pulmonary fibrosis
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory system disease-0.11KE:1226Increased Respiratory irritability and Chronic Cough,
AOP:205AOP from chemical insult to cell deathUnclassified-Vertebrates0.33KE:1263Necrosis
KE:1262Apoptosis
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder DevelopmentHomo sapiens0.33KE:149Increase, Inflammation
KE:1276Lung fibrosis
AOP:241Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosisMusculoskeletal system disease; Respiratory system disease-0.33KE:68Accumulation, Collagen
KE:1458Pulmonary fibrosis
AOP:260CYP2E1 activation and formation of protein adducts leading to neurodegenerationNervous system disease-Human0.43KE:1392Oxidative Stress
KE:1514Neurodegeneration
KE:1513General Apoptosis
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.57KE:155Inadequate DNA repair
KE:870Increase, Cell Proliferation
KE:1636Increase, Chromosomal aberrations
KE:1556Increase, lung cancer
AOP:278IKK complex inhibition leading to liver injuryUnclassified-0.12KE:1549Liver Injury
AOP:281Acetylcholinesterase Inhibition Leading to NeurodegenerationNervous system disease-0.1KE:352N/A, Neurodegeneration
AOP:296Oxidative DNA damage leading to chromosomal aberrations and mutationsGenetic disease; Chromosomal diseaseWPHA/WNT EndorsedHuman, Mice, Rat, Fish0.4KE:155Inadequate DNA repair
KE:1636Increase, Chromosomal aberrations
AOP:302Lung surfactant function inhibition leading to decreased lung functionRespiratory system diseaseUnder DevelopmentHuman, Mouse, Rat0.2KE:1250Decrease, Lung function
AOP:303Frustrated phagocytosis-induced lung cancerCancerUnder DevelopmentMammals0.71KE:1115Increase, Reactive oxygen species
KE:870Increase, Cell Proliferation
KE:1670Lung cancer
KE:1669Increased, DNA damage and mutation
KE:1497Increased, recruitment of inflammatory cells
AOP:347Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosisMusculoskeletal system disease; Respiratory system disease-0.11KE:1458Pulmonary fibrosis
AOP:379Binding to ACE2 leading to thrombosis and disseminated intravascular coagulationCardiovascular system diseaseUnder DevelopmentHomo sapiens0.29KE:1846Thrombosis and Disseminated Intravascular Coagulation
KE:1869Diminished protective oxidative stress response
AOP:382Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder Development0.67KE:68Accumulation, Collagen
KE:1115Increase, Reactive oxygen species
KE:1496Increased, secretion of proinflammatory mediators
KE:1276Lung fibrosis
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder DevelopmentHumans0.6KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
KE:1496Increased, secretion of proinflammatory mediators
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.5KE:1869Diminished protective oxidative stress response
KE:1868Hyperinflammation
KE:1895NLRP3 inflammasome activity, increased
AOP:414Aryl hydrocarbon receptor activation leading to lung fibrosis through TGF-β dependent fibrosis toxicity pathwayMusculoskeletal system disease; Respiratory system disease-0.4KE:1920Altered gene expression, TGF-β dependent fibrosis pathway
KE:1276Lung fibrosis
AOP:415Aryl hydrocarbon receptor activation leading to lung fibrosis through IL-6 toxicity pathwayMusculoskeletal system disease; Respiratory system disease-0.2KE:1276Lung fibrosis
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.5KE:1669Increased, DNA damage and mutation
KE:1115Increase, Reactive oxygen species
KE:1670Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.4KE:1669Increased, DNA damage and mutation
KE:1670Lung cancer
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.4KE:1250Decrease, Lung function
KE:1115Increase, Reactive oxygen species
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.5KE:1250Decrease, Lung function
KE:1262Apoptosis
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.5KE:870Increase, Cell Proliferation
KE:1670Lung cancer
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.67KE:1115Increase, Reactive oxygen species
KE:870Increase, Cell Proliferation
KE:1669Increased, DNA damage and mutation
KE:1670Lung cancer
KE:1496Increased, secretion of proinflammatory mediators
KE:1497Increased, recruitment of inflammatory cells
AOP:452Adverse outcome pathway of PM-induced respiratory toxicityRespiratory system disease-0.27KE:1392Oxidative Stress
KE:2008Chronic obstructive pulmonary disease
KE:1262Apoptosis
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-0.38KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
KE:1496Increased, secretion of proinflammatory mediators
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular system diseaseUnder ReviewHuman, Rat, Mouse, Rabbit0.5KE:1493Increased Pro-inflammatory mediators
KE:1392Oxidative Stress
KE:2069Occurrence, Abnormal Vascular Remodeling
KE:2244Altered Stress Response Signaling
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE:885Increase, Cancer
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:2119Insulin resistance, increased
KE:1115Increase, Reactive oxygen species
AOP:534Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stressCancer-Vertebrates0.67KE:1392Oxidative Stress
KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:546Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanismsCancer-Human and other cells in culture0.2KE:885Increase, Cancer
AOP:573Inhibition, cytochrome oxidase leads to Increased, pulmonary edemaRespiratory system disease-Rodents, Humans0.33KE:2316Increased, pulmonary edema

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:62AKT2 activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.25KE:486systemic inflammation leading to hepatic steatosis
AOP:118Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)Cancer; Gastrointestinal system disease-Mus musculus, Rattus norvegicus0.5KE:786Increase, Cytotoxicity (hepatocytes)
KE:787Increase, Regenerative cell proliferation (hepatocytes)
AOP:232NFE2/Nrf2 repression to steatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:1417NFE2/Nrf2 repression
AOP:263Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferationUnclassifiedWPHA/WNT EndorsedZebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans0.75KE:1771Decrease, Adenosine triphosphate pool
KE:1446Decrease, Coupling of oxidative phosphorylation
KE:1821Decrease, Cell proliferation
AOP:264Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell deathUnclassifiedUnder Development0.5KE:1771Decrease, Adenosine triphosphate pool
KE: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 Development0.33KE:1771Decrease, Adenosine triphosphate pool
KE: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:282Adverse outcome pathway on photochemical toxicity initiated by light exposureUnclassifiedUnder ReviewHuman0.25KE:1115Increase, Reactive oxygen species
AOP:298Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROSCancer; Gastrointestinal system diseaseUnder ReviewHomo sapiens0.33KE:1753Chronic reactive oxygen species
KE:1115Increase, Reactive oxygen species
AOP:324Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell deathUnclassified-Fish0.25KE:1115Increase, Reactive oxygen species
AOP:325Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell deathUnclassified-Fish0.25KE:1115Increase, Reactive oxygen species
AOP:326Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell deathUnclassified-Fish0.25KE:1115Increase, Reactive oxygen species
AOP:327Excessive reactive oxygen species production leading to mortality (1)Unclassified-Daphnia magna0.2KE:1115Increase, Reactive oxygen species
AOP:328Excessive reactive oxygen species production leading to mortality (2)Unclassified-Daphnia magna0.4KE:1771Decrease, Adenosine triphosphate pool
KE:1115Increase, Reactive oxygen species
AOP:329Excessive reactive oxygen species production leading to mortality (3)Unclassified-Daphnia magna, Paracyclopina nana0.4KE:1771Decrease, Adenosine triphosphate pool
KE:1115Increase, Reactive oxygen species
AOP:330Excessive reactive oxygen species production leading to mortality (4)Unclassified-Daphnia magna0.4KE:1365Increase, Apoptosis
KE:1115Increase, Reactive oxygen species
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 parvula0.33KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:332Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferationUnclassified-0.4KE:1821Decrease, Cell proliferation
KE:1115Increase, Reactive oxygen species
AOP:333Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylationUnclassified-0.8KE:1821Decrease, Cell proliferation
KE:1771Decrease, Adenosine triphosphate pool
KE:1115Increase, Reactive oxygen species
KE:1446Decrease, Coupling of oxidative phosphorylation
AOP:423Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathwayUnclassified-0.17KE:1115Increase, Reactive oxygen species
AOP:438reactive oxygen species generation leading to increased cardiovascular morbidity and mortalityCardiovascular system disease-0.17KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:443DNA damage and mutations leading to Metastatic Breast CancerThoracic disease; CancerUnder DevelopmentHuman and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast0.3KE:155Inadequate DNA repair
KE:1669Increased, DNA damage and mutation
KE:1554Increase Chromosomal Aberrations
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.5KE:1115Increase, Reactive oxygen species
KE:1458Pulmonary fibrosis
KE:1993Increase, Pneumonia
KE:1392Oxidative Stress
KE:1250Decrease, Lung function
KE:1496Increased, secretion of proinflammatory mediators
KE:1198Activation, Macrophages
KE:1497Increased, recruitment of inflammatory cells
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:448ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortalityCardiovascular system disease-0.24KE:1392Oxidative Stress
KE:1198Activation, Macrophages
KE:2003Vascular remodeling
KE:1115Increase, Reactive oxygen species
AOP:453Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general populationGastrointestinal system disease-0.31KE:1392Oxidative Stress
KE:1198Activation, Macrophages
KE:2016Hepatocyte cell apoptosis
KE:1115Increase, Reactive oxygen species
AOP:469Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation populationGastrointestinal system disease-0.31KE:1392Oxidative Stress
KE:1198Activation, Macrophages
KE:2016Hepatocyte cell apoptosis
KE:1115Increase, Reactive oxygen species
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.33KE:1392Oxidative Stress
KE:149Increase, Inflammation
KE:1115Increase, Reactive oxygen species
AOP:488Increased reactive oxygen species production leading to decreased cognitive functionCognitive disorder-Human0.43KE:1392Oxidative Stress
KE:1869Diminished protective oxidative stress response
KE:1115Increase, Reactive oxygen species
AOP:507Nrf2 inhibition leading to vascular disrupting effects via inflammation pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.33KE:1392Oxidative Stress
KE:1417NFE2/Nrf2 repression
AOP:508Nrf2 inhibition leading to vascular disrupting effects through activating HIF1α, Semaphorin 6A, and Dll4-Notch pathwayCardiovascular system disease-Mouse, Zebrafish, Human0.14KE:1417NFE2/Nrf2 repression
AOP:509Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunctionCardiovascular system disease-0.43KE:1392Oxidative Stress
KE:1417NFE2/Nrf2 repression
KE:1365Increase, Apoptosis
AOP:511The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effectsCardiovascular system disease-Human, Mouse, Zebrafish0.12KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.33KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species
KE:1262Apoptosis
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.31KE:1493Increased Pro-inflammatory mediators
KE:1198Activation, Macrophages
KE:1392Oxidative Stress
KE:1115Increase, Reactive oxygen species

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:411Oxidative stress Leading to Decreased Lung FunctionRespiratory system disease-Homo sapiens0.5KE:1392Oxidative Stress
KE:1250Decrease, Lung function
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory system disease-Human0.33KE:1392Oxidative Stress
KE:1250Decrease, Lung function
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory system disease-Human0.33KE:1392Oxidative Stress
KE:1250Decrease, Lung function
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.45KE:1115Increase, Reactive oxygen species
KE:1392Oxidative Stress
KE:2034liver dysfunction
KE:149Increase, Inflammation
KE:1262Apoptosis
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat1.0KE:1513General Apoptosis
KE:1115Increase, Reactive oxygen species
KE:1392Oxidative Stress
KE:885Increase, Cancer
KE:149Increase, Inflammation
AOP:513Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathwayCancer-Human, Mouse, Rat0.8KE:1513General Apoptosis
KE:885Increase, Cancer
KE:1115Increase, Reactive oxygen species
KE:1060Alteration, lipid metabolism

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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.