title: Comparative hepatotoxicity of 6:2 fluorotelomer carboxylic acid and 6:2 fluorotelomer sulfonic acid, two fluorinated alternatives to long-chain perfluoroalkyl acids, on adult male mice.
abstract: Due to their structural similarities, 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and 6:2 fluorotelomer carboxylic acid (6:2 FTCA) are often used as alternatives to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), respectively. With limited health risk data and 6:2 FTSA detection in water and sludge, the toxicity of these chemicals is of growing concern. Here, adult male mice were exposed with 5 mg/kg/day of 6:2 FTCA or 6:2 FTSA for 28 days to investigate their hepatotoxicological effects. In contrast to 6:2 FTCA, 6:2 FTSA was detected at high and very high levels in serum and liver, respectively, demonstrating bioaccumulation potential and slow elimination. Furthermore, 6:2 FTSA induced liver weight increase, inflammation, and necrosis, whereas 6:2 FTCA caused no obvious liver injury, with fewer significantly altered genes detected compared with that of 6:2 FTSA (39 vs. 412). Although PFOA and PFOS commonly activate peroxisome proliferator-activated receptor α (PPARα), 6:2 FTSA induced an increase in PPARγ and related proteins, but not in lipid metabolism-related genes such as PPARα. Our results showed that 6:2 FTCA and 6:2 FTSA exhibited weak and moderate hepatotoxicity, respectively, compared with that reported for legacies PFOA and PFOS.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sheng
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 210029, People's Republic of China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China. daijy@ioz.ac.cn.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity; D000818:Animals; D002210:Caprylates / Q000633:toxicity; D002264:Carboxylic Acids / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D005466:Fluorocarbons / Q000633:toxicity; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D013451:Sulfonic Acids / Q000633:toxicity*
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D002264:Carboxylic Acids; D005466:Fluorocarbons; D047493:PPAR alpha; D047495:PPAR gamma; D013451:Sulfonic Acids; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: 6:2 FTCA; 6:2 FTSA; Comparative hepatotoxicity; PFAAs alternatives