title: Fluorinated alkyl substances and technical mixtures used in food paper-packaging exhibit endocrine-related activity in vitro.
abstract: Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. In general, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17β-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARα and PPARγ. Collectively, this means that (i) PAPs, FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMs exhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate both PPARα and PPARγ with similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicological targets were identified for different groups of PFAS.
authors.affiliation: Division of Diet, Disease Prevention, and Toxicology, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: A K
authors.initials: AK
authors.lastname: Rosenmai
authors.affiliation: Division of Diet, Disease Prevention, and Toxicology, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Taxvig
authors.affiliation: Division of Diet, Disease Prevention, and Toxicology, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Svingen
authors.affiliation: Research Group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: X
authors.initials: X
authors.lastname: Trier
authors.affiliation: BioDetection Systems b.v., Amsterdam, The Netherlands.
authors.forename: B M A
authors.initials: BM
authors.lastname: van Vugt-Lussenburg
authors.affiliation: Research Group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, Rennes CEDEX, France.|Université de Rennes I, Rennes CEDEX, France.
authors.forename: L
authors.initials: L
authors.lastname: Lesné
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, Rennes CEDEX, France.|Université de Rennes I, Rennes CEDEX, France.|EHESP - School of Public Health, Rennes CEDEX, France.
authors.forename: B
authors.initials: B
authors.lastname: Jégou
authors.affiliation: Division of Diet, Disease Prevention, and Toxicology, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Vinggaard
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D006845:Hydrocarbons, Fluorinated; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol
keywords: estrogenic activity; fluorotelomer alcohols; perfluoroalkyl carboxylic acids; peroxisome proliferator-activated receptor; polyfluorinated alkyl phosphate esters; polyfluoroalkyl substances