Perfluoroalkylated substances (PFAS) affect neither estrogen and androgen receptor activity nor steroidogenesis in human cells in vitro. (July 2018)

• Record Type: Journal Article
• Authors: Behr, Anne-Cathrin; Lichtenstein, Dajana; Braeuning, Albert; Lampen, Alfonso; Buhrke, Thorsten
• Is Part Of: Toxicology letters. Volume 291(2018)
• Page Start: 51
• Page End: 60
• Publication Date: 2018-07
• Subjects: Perfluoroalkylated substances (PFAS) -- PFOA -- PFOS -- Steroidogenesis -- Androgen receptor -- Estrogen receptor; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.03.029
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: PFAS did not directly activate human ERα, ERβ and AR. Some PFAS enhanced agonist-stimulated ERα, ERβ and AR activity. PFAS did not stimulate proliferation of MCF-7 cells. Only PFOA and PFOS had a slight impact on steroidogenesis in H295R cells. PFAS displayed no endocrine properties in vitro at concentrations relevant for human exposure. Abstract: The perfluoroalkylated substances (PFAS) perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are used for the fabrication of water- and dirt-repellent surfaces. The use of PFOS and PFOA was restricted due to their reprotoxic properties and their environmental persistence. Therefore, industry switches to alternative PFAS, however, in contrast to PFOA and PFOS only few toxicological data are available for their substitutes. The molecular mechanism(s) underlying reproductive toxicity of PFOA and PFOS are largely unknown. Here, the endocrine properties of PFOA, PFOS, and of six substitutes including perfluorohexanesulfonic acid (PFHxS), perfluorobutanesulfonic acid (PFBS), perfluorohexanoic acid (PFHxA), perfluorobutanoic acid (PFBA), ammonium perfluoro(2-methyl-3-oxahexanoate) (PMOH), and 3H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP) were examined in vitro by using human cell lines such as MCF-7, H295R, LNCaP and MDA-kb2. PFOA, PFOS and PMOH enhanced 17β-estradiol-stimulated estrogen receptor β activity, and PFOS, PMOH, PFHxA and PFBA enhanced dihydrotestosterone-stimulated androgen receptor activity. In the H295R steroidogenesis assay, PFOA and PFOS slightly enhanced estrone secretion, and progesterone secretion was marginally increased by PFOA. All these effects were only observed at concentrations above 10 μM, and none of the PFAS displayed any effect on any of the molecular endocrine endpoints at concentrations of 10 μM or below. Thus, as the blood serum concentrations of the different PFAS in the general Western population are in the range of 10 nM or below, the results suggest that PFAS might not exert endocrine effects in humans at exposure-relevant concentrations according to the molecular endpoints examined in this study.