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In vitro activity of a panel of per- and polyfluoroalkyl substances (PFAS), fatty acids, and pharmaceuticals in peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma, and estrogen receptor assays.
Evans, Nicola; Conley, Justin M; Cardon, Mary; Hartig, Phillip; Medlock-Kakaley, Elizabeth; Gray, L Earl.
Afiliación
  • Evans N; U.S. Environmental Protection Agency/Office of Research & Development/Center for Public Health and Environmental Assessment/Public Health and Integrated Toxicology Division, Research Triangle Park, NC 27711, USA. Electronic address: evans.nicola@epa.gov.
  • Conley JM; U.S. Environmental Protection Agency/Office of Research & Development/Center for Public Health and Environmental Assessment/Public Health and Integrated Toxicology Division, Research Triangle Park, NC 27711, USA. Electronic address: conley.justin@epa.gov.
  • Cardon M; U.S. Environmental Protection Agency/Office of Research & Development/Center for Public Health and Environmental Assessment/Public Health and Integrated Toxicology Division, Research Triangle Park, NC 27711, USA. Electronic address: cardon.mary@epa.gov.
  • Hartig P; U.S. Environmental Protection Agency/Office of Research & Development/Center for Public Health and Environmental Assessment/Public Health and Integrated Toxicology Division, Research Triangle Park, NC 27711, USA. Electronic address: hartig.phillip@epa.gov.
  • Medlock-Kakaley E; U.S. Environmental Protection Agency/Office of Research & Development/Center for Public Health and Environmental Assessment/Public Health and Integrated Toxicology Division, Research Triangle Park, NC 27711, USA. Electronic address: medlockkakaley.elizabeth@epa.gov.
  • Gray LE; U.S. Environmental Protection Agency/Office of Research & Development/Center for Public Health and Environmental Assessment/Public Health and Integrated Toxicology Division, Research Triangle Park, NC 27711, USA. Electronic address: gray.earl@epa.gov.
Toxicol Appl Pharmacol ; 449: 116136, 2022 08 15.
Article en En | MEDLINE | ID: mdl-35752307
Data demonstrate numerous per- and polyfluoroalkyl substances (PFAS) activate peroxisome proliferator-activated receptor alpha (PPARα), however, additional work is needed to characterize PFAS activity on PPAR gamma (PPARγ) and other nuclear receptors. We utilized in vitro assays with either human or rat PPARα or PPARγ ligand binding domains to evaluate 16 PFAS (HFPO-DA, HFPO-DA-AS, NBP2, PFMOAA, PFHxA, PFOA, PFNA, PFDA, PFOS, PFBS, PFHxS, PFOSA, EtPFOSA, and 4:2, 6:2 and 8:2 FTOH), 3 endogenous fatty acids (oleic, linoleic, and octanoic), and 3 pharmaceuticals (WY14643, clofibrate, and the metabolite clofibric acid). We also tested chemicals for human estrogen receptor (hER) transcriptional activation. Nearly all compounds activated both PPARα and PPARγ in both human and rat ligand binding domain assays, except for the FTOH compounds and PFOSA. Receptor activation and relative potencies were evaluated based on effect concentration 20% (EC20), top percent of max fold induction (pmaxtop), and area under the curve (AUC). HFPO-DA and HFPO-DA-AS were the most potent (lowest EC20, highest pmaxtop and AUC) of all PFAS in rat and human PPARα assays, being slightly less potent than oleic and linoleic acid, while NBP2 was the most potent in rat and human PPARγ assays. Only PFHxS, 8:2 and 6:2 FTOH exhibited hER agonism >20% pmax. In vitro measures of human and rat PPARα and PPARγ activity did not correlate with oral doses or serum concentrations of PFAS that induced increases in male rat liver weight from the National Toxicology Program 28-d toxicity studies. Data indicate that both PPARα and PPARγ activation may be molecular initiating events that contribute to the in vivo effects observed for many PFAS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: PPAR alfa / Fluorocarburos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: PPAR alfa / Fluorocarburos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos