title: Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor.
abstract: Perfluoroalkyl acids (PFAAs) are perfluorinated compounds that widely exist in the environment and can elicit adverse effects including endocrine disruption in humans and animals. This study investigated the effect of seven PFAAs on the thyroid hormone (TH) system assessing the proliferation of the 3,3',5-triiodo-L-thryonine (T3)-dependent rat pituitary GH3 cells using the T-screen assay and the effect on the aryl hydrocarbon receptor (AhR) transactivation in the AhR-luciferase reporter gene bioassay. A dose-dependent impact on GH3 cells was observed in the range 1×10(-9)-1×10(-4) M: seven PFAAs (perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorododecanoic acid (PFDoA)) inhibited the GH3 cell growth, and four PFAAs (PFOS, PFHxS, PFNA, and PFUnA) antagonized the T3-induced GH3 cell proliferation. At the highest test concentration, PFHxS showed a further increase of the T3-induced GH3 growth. Among the seven tested PFAAs, only PFDoA and PFDA elicited an activating effect on the AhR. In conclusion, PFAAs possess in vitro endocrine-disrupting potential by interfering with TH and AhR functions, which need to be taken into consideration when assessing the impact on human health.
authors.affiliation: Centre for Arctic Health and Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Alle 2, Building 1260, 8000, Aarhus C, Denmark, ml@mil.au.dk.
authors.forename: Manhai
authors.initials: M
authors.lastname: Long
authors.forename: Mandana
authors.initials: M
authors.lastname: Ghisari
authors.forename: Eva Cecilie
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
mesh_terms: D000818:Animals; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D015386:Hazardous Substances / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D018570:Risk Assessment; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D005466:Fluorocarbons; D015386:Hazardous Substances; D018336:Receptors, Aryl Hydrocarbon; D013963:Thyroid Hormones
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