Carbon


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:4Ecdysone receptor agonism leading to incomplete ecdysis associated mortalityUnclassified-Insects, Crustaceans0.2KE:1265Increase, Fushi tarazu factor-1 gene expression
KE:1264Increase, Nuclear receptor E75b gene expression
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:8Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in MammalsNervous system diseaseUnder DevelopmentRat0.11KE:756Hippocampal gene expression, Altered
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:381Reduced levels of BDNF
AOP:13Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilitiesDevelopmental disorder of mental healthWPHA/WNT EndorsedHuman, Mouse, Monkey sp., Rat0.1KE:381Reduced levels of BDNF
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, Human0.1KE:1493Increased Pro-inflammatory mediators
AOP:18PPARα activation in utero leading to impaired fertility in malesReproductive system diseaseUnder ReviewHuman, Rat, Mouse0.12KE:289Decrease, Translocator protein (TSPO)
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:21Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2UnclassifiedWPHA/WNT EndorsedZebrafish, Medaka, Gallus gallus0.2KE:1269Increase, COX-2 expression
AOP:23Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)UnclassifiedWPHA/WNT EndorsedPimephales promelas0.3KE:285Reduction, Vitellogenin synthesis in liver
KE: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, Zebrafish0.38KE:285Reduction, Vitellogenin synthesis in liver
KE: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 DevelopmentHumans0.25KE:149Increase, Inflammation
KE:288Activation of specific nuclear receptors, Transcriptional change
AOP:30Estrogen receptor antagonism leading to reproductive dysfunctionUnclassifiedUnder ReviewZebra danio, Fathead minnow, Medaka0.17KE:285Reduction, Vitellogenin synthesis in liver
AOP:34LXR activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.15KE:54Up Regulation, CD36
KE:258Activation, SCD-1
AOP:36Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to SteatosisGastrointestinal system disease; Inherited metabolic disorder-0.12KE:140Decreased, HSD17B10 expression
AOP:38Protein Alkylation leading to Liver FibrosisGastrointestinal system diseaseWPHA/WNT EndorsedHuman, Rat0.14KE:1493Increased Pro-inflammatory mediators
AOP:42Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderWPHA/WNT EndorsedHuman, Rat, Mouse0.12KE:756Hippocampal gene expression, Altered
AOP:54Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairmentDevelopmental disorder of mental healthWPHA/WNT EndorsedHomo sapiens, Rattus sp.0.1KE:381Reduced levels of BDNF
AOP:58NR1I3 (CAR) suppression leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-Human, Mouse, Rat0.19KE:54Up Regulation, CD36
KE:463Up Regulation, FAS
KE:462Up Regulation, SCD-1
AOP:60NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.33KE:474Down Regulation, HMGCS2
KE:462Up Regulation, SCD-1
KE:472Down Regulation, CPT1A
KE:54Up Regulation, CD36
AOP:64Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male FertilityReproductive system disease-Rattus norvegicus0.14KE:520Decreased sperm quantity or quality in the adult, Decreased fertility
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:114HPPD inhibition leading to corneal papillomas and carcinomas (in rat)Cancer-Rattus norvegicus0.17KE:777Increase, Inflammation (corneal cells)
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 promelas0.4KE:799Increased, HIF-1 heterodimer
KE:285Reduction, Vitellogenin synthesis in liver
KE: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 promelas0.45KE:802Increased, HIF-1 alpha transcription
KE:285Reduction, Vitellogenin synthesis in liver
KE:799Increased, HIF-1 heterodimer
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:131Aryl hydrocarbon receptor activation leading to uroporphyriaInherited metabolic disorderWPHA/WNT EndorsedMouse, Rat, Human, Japanese quail, Chicken, Herring gull, Common Starling0.17KE:850Induction, CYP1A2/CYP1A5
AOP:134Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Homo sapiens0.11KE:756Hippocampal gene expression, Altered
AOP:144Endocytic lysosomal uptake leading to liver fibrosisGastrointestinal system diseaseUnder ReviewHuman, Mouse, Rat0.11KE:1493Increased Pro-inflammatory mediators
AOP:150Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGFUnclassifiedWPHA/WNT EndorsedChicken, Zebrafish, Mouse, Rattus norvegicus0.14KE:948reduced production, VEGF
AOP:151AhR activation leading to preeclampsiaCardiovascular system diseaseUnder DevelopmentHomo sapiens, Mus musculus0.29KE:1892increase, placental insufficiency
KE:948reduced production, VEGF
AOP:167Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.Reproductive system disease; Cancer-Mouse, Homo sapiens0.14KE:1066Promotion, SIX-1 postive basal-type progenitor cells
AOP:173Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosisMusculoskeletal system disease; Respiratory system diseaseWPHA/WNT EndorsedHuman, Mouse, Rat0.12KE:1497Increased, recruitment of inflammatory cells
AOP:201Juvenile hormone receptor agonism leading to male offspring induction associated population declineUnclassified-Daphnia magna, Daphnia pulex0.17KE:1206Induction, Doublesex1 gene
AOP:206Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosisMusculoskeletal system disease; Respiratory system diseaseUnder DevelopmentHomo sapiens0.17KE:149Increase, Inflammation
AOP:218Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activityUnclassified-Japanese quail, Cynops pyrrhogaster0.17KE:1141Decreased, Reproductive Success
AOP:219Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behaviorUnclassified-Japanese quail, Cynops pyrrhogaster0.17KE:1141Decreased, Reproductive Success
AOP:271Inhibition of thyroid peroxidase leading to impaired fertility in fishUnclassifiedUnder DevelopmentFish0.2KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:275Histone deacetylase inhibition leads to neural tube defectsNeural tube defect-0.2KE:1239Altered, Gene Expression
AOP:280α-diketone-induced bronchiolitis obliteransMusculoskeletal system disease; Respiratory system disease-0.14KE:149Increase, Inflammation
AOP:289Inhibition of 5α-reductase leading to impaired fecundity in female fishUnclassifiedUnder DevelopmentFish0.17KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:293Increased DNA damage leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder DevelopmentRattus rattus, Mus musculus0.11KE:1493Increased Pro-inflammatory mediators
AOP:294Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancerGenetic disease; Thoracic disease; CancerUnder Development0.11KE:1493Increased Pro-inflammatory mediators
AOP:300Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorderUnder DevelopmentHuman, Mouse0.2KE:756Hippocampal gene expression, Altered
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:310Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHRUnclassified-Zebrafish0.25KE:285Reduction, Vitellogenin synthesis in liver
KE:219Reduction, Plasma 17beta-estradiol concentrations
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa 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: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:362Immune mediated hepatitisGastrointestinal system disease; Immune system disease-Homo sapiens, Rat0.12KE: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:409Frustrated phagocytosis leads to malignant mesotheliomaCancer-0.12KE:1497Increased, recruitment of inflammatory cells
AOP:432Deposition of Energy by Ionizing Radiation leading to Acute Myeloid LeukemiaHematopoietic system disease; Cancer-Homo sapiens, Mus musculus0.09KE:1493Increased Pro-inflammatory mediators
AOP:439Activation of the AhR leading to metastatic breast cancerThoracic disease; CancerUnder DevelopmentHumans, Mice0.11KE:149Increase, Inflammation
AOP:447Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathwaysUrinary system disease-0.08KE:1633Increase in inflammation
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, Chicken0.33KE:2020Decrease, sox9 expression
KE:2021Increase, slincR expression
AOP:456Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicityUnclassifiedUnder ReviewZebrafish, Mouse, Human, Chicken0.33KE:2020Decrease, sox9 expression
KE:2021Increase, slincR expression
AOP:458AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Rat, Mouse, Monkey, Human0.12KE:756Hippocampal gene expression, Altered
AOP:459AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in MammalsCognitive disorder-Human, Mouse, Rat0.22KE:756Hippocampal gene expression, Altered
KE:850Induction, CYP1A2/CYP1A5
AOP:460Antagonism of Smoothened receptor leading to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.11KE:2040Decrease, GLI1/2 target gene expression
AOP:463The AOP framwork on silica nanopariticles induced hepatoxicityGastrointestinal system disease-0.09KE:149Increase, Inflammation
AOP:470Deposition of energy leads to abnormal vascular remodelingCardiovascular system diseaseUnder ReviewHuman, Rat, Mouse, Rabbit0.12KE:1493Increased Pro-inflammatory mediators
AOP:472DNA adduct formation leading to kidney failureUrinary system disease-0.11KE:149Increase, Inflammation
AOP:493ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesityAcquired metabolic disease-Mus musculus, Homo sapiens0.2KE:1633Increase in inflammation
KE:1497Increased, recruitment of inflammatory cells
AOP:495Androgen receptor activation leading to prostate cancerReproductive system disease; Cancer-0.11KE:286Altered, Transcription of genes by the androgen receptor
AOP:496Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)Unclassified-Zebrafish0.2KE:286Altered, Transcription of genes by the androgen receptor
KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:517Pregnane X Receptor (PXR) activation leads to liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates0.2KE:54Up Regulation, CD36
AOP:529Perfluorooctanesulfonic acid (PFOS) binding to peroxisome proliferator-activated receptors (PPARs) causes dysregulation of lipid metabolism and subsequent liver steatosisGastrointestinal system disease; Inherited metabolic disorder-Vertebrates, Mouse, Rat, Zebrafish0.12KE:2224Dysregulation of transcriptional expression within PPAR signaling network
AOP:533Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memoryDevelopmental disorder of mental health-0.17KE:1239Altered, Gene Expression
AOP:536Estrogen receptor agonism leading to reduced survival and population growth due to renal failureUnclassified-0.17KE:307Increase, Vitellogenin synthesis in liver
AOP:537Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liverUnclassified-0.2KE:307Increase, Vitellogenin synthesis in liver
AOP:540Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin ProductionUnclassified-0.22KE:285Reduction, Vitellogenin synthesis in liver
KE:3Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:541Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switchingCardiovascular system disease-0.08KE:1493Increased Pro-inflammatory mediators
AOP:544Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammationNervous system disease-Homo sapiens, Mus musculus0.17KE:149Increase, Inflammation
AOP:549Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafishUnclassified-0.12KE:219Reduction, Plasma 17beta-estradiol concentrations
AOP:550Increased LMNA gene mutation leading to heart failureCardiovascular system disease-Human, Mouse, Rat0.2KE:2066Altered Signaling Pathways

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:139Alkylation of DNA leading to cancer 1Cancer-Homo sapiens, Mus musculus0.25KE:885Increase, Cancer
AOP:148EGFR Activation Leading to Decreased Lung FunctionRespiratory system diseaseUnder DevelopmentHuman, Mouse, Rat0.5KE:1250Decrease, Lung function
KE:962Increase, Mucin production
AOP:196Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary IrritationRespiratory system disease-0.11KE:1226Increased Respiratory irritability and Chronic Cough,
AOP:2035-hydroxytryptamine transporter inhibition leading to decreased reproductive success and population declineReproductive system disease-0.12KE:1141Decreased, Reproductive Success
AOP:272Deposition of energy leading to lung cancerCancerWPHA/WNT EndorsedHuman, Rat, Mouse0.14KE:1556Increase, lung cancer
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 DevelopmentMammals0.29KE:1497Increased, recruitment of inflammatory cells
KE:1670Lung cancer
AOP:322Alkylation of DNA leading to reduced sperm countReproductive system disease-0.2KE:1757Reduce, Sperm count
AOP:392Decreased fibrinolysis and activated bradykinin system leading to hyperinflammationUnclassifiedUnder DevelopmentHumans0.4KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
AOP:406SARS-CoV-2 infection leading to hyperinflammationUnclassified-0.17KE:1868Hyperinflammation
AOP:411Oxidative stress Leading to Decreased Lung FunctionRespiratory system disease-Homo sapiens0.25KE:1250Decrease, Lung function
AOP:416Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathwayCancer-0.17KE:1670Lung cancer
AOP:417Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathwayCancer-0.2KE:1670Lung cancer
AOP:418Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathwayRespiratory system disease-0.2KE:1250Decrease, Lung function
AOP:419Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathwayRespiratory system disease-0.25KE:1250Decrease, Lung function
AOP:420Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathwayCancer-0.25KE:1670Lung cancer
AOP:424Oxidative stress Leading to Decreased Lung Function via CFTR dysfunctionRespiratory system disease-Human0.17KE:1250Decrease, Lung function
AOP:425Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1Respiratory system disease-Human0.17KE:1250Decrease, Lung function
AOP:451Interaction with lung resident cell membrane components leads to lung cancerCancer-Human0.22KE:1497Increased, recruitment of inflammatory cells
KE:1670Lung cancer
AOP:468Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)Unclassified-0.25KE:1868Hyperinflammation
KE:1497Increased, recruitment of inflammatory cells
AOP:474Succinate dehydrogenase inactivation leads to cancer by promoting EMTCancerUnder DevelopmentHuman and other cells in culture0.2KE:885Increase, Cancer
AOP:505Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathwayCancer-Human, Mouse, Rat0.4KE:885Increase, Cancer
KE:149Increase, Inflammation
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:62AKT2 activation leading to hepatic steatosisGastrointestinal system disease; Inherited metabolic disorder-0.25KE:486systemic inflammation leading to hepatic steatosis
AOP:209Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOPGastrointestinal system disease-0.12KE:1284Up Regulation, SREBF2
AOP:446PM-related Adverse outcome pathway frameworks on various systemsRespiratory system disease-0.2KE:1239Altered, Gene Expression
KE:1250Decrease, Lung function
KE:149Increase, Inflammation
KE:1497Increased, recruitment of inflammatory cells
AOP:491Decrease, GLI1/2 target gene expression leads to orofacial cleftingUnclassifiedUnder DevelopmentMouse0.17KE:2040Decrease, GLI1/2 target gene expression

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.