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Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice.
Environ Sci Technol. 2018 11 06; 52(21):12809-12818.ES

Abstract

The compound 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative to perfluorooctanesulfonate (PFOS) in the metal-plating industry, has been widely detected in various environmental matrices. However, its hepatotoxicity has yet to be clarified. Here, male mice were exposed to 0.04, 0.2, or 1 mg/kg/day of 6:2 Cl-PFESA for 56 days. Results demonstrated that relative liver weight increased significantly in the 0.2 and 1 mg/kg/day 6:2 Cl-PFESA groups, whereas liver lipid accumulation increased in all 6:2 Cl-PFESA groups. Serum enzyme activities of alanine transaminase and alkaline phosphatase were increased. Serum triglycerides and low-density lipoprotein cholesterol both increased, whereas serum total cholesterol and high-density lipoprotein cholesterol decreased following 6:2 Cl-PFESA exposure. A total of 264 differentially expressed proteins (127 up-regulated and 137 down-regulated), mainly involved in lipid metabolism, xenobiotic metabolism, and ribosome biogenesis, were identified by quantitative proteomics. Bioinformatics analysis highlighted the de-regulation of PPAR and PXR, which may contribute to the hepatotoxicity of 6:2 Cl-PFESA. Additionally, 6:2 Cl-PFESA induced both cell apoptosis and proliferation in the mouse liver. Compared to the overt toxicity of PFOS, 6:2 Cl-PFESA exhibited more-serious hepatotoxicity. Thus, caution should be exercised in the application of 6:2 Cl-PFESA as a replacement alternative to PFOS in industrial areas.

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Authors+Show Affiliations

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

Key Laboratory of Organofluorine Chemistry , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , Shanghai 200032 , China.

Key Laboratory of Organofluorine Chemistry , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , Shanghai 200032 , China.

Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

MeSH

Alkanesulfonic AcidsAnimalsChemical and Drug Induced Liver InjuryEtherEthersFluorocarbonsLiverMaleMice

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30256107

Citation

Zhang, Hongxia, et al. "Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, On Adult Male Mice." Environmental Science & Technology, vol. 52, no. 21, 2018, pp. 12809-12818.

Zhang H, Zhou X, Sheng N, et al. Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice. Environ Sci Technol. 2018;52(21):12809-12818.

Zhang, H., Zhou, X., Sheng, N., Cui, R., Cui, Q., Guo, H., Guo, Y., Sun, Y., & Dai, J. (2018). Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice. Environmental Science & Technology, 52(21), 12809-12818. https://doi.org/10.1021/acs.est.8b04368

Zhang H, et al. Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, On Adult Male Mice. Environ Sci Technol. 2018 11 6;52(21):12809-12818. PubMed PMID: 30256107.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice. AU - Zhang,Hongxia, AU - Zhou,Xiujuan, AU - Sheng,Nan, AU - Cui,Ruina, AU - Cui,Qianqian, AU - Guo,Hua, AU - Guo,Yong, AU - Sun,Yan, AU - Dai,Jiayin, Y1 - 2018/10/10/ PY - 2018/9/27/pubmed PY - 2019/9/19/medline PY - 2018/9/27/entrez SP - 12809 EP - 12818 JF - Environmental science & technology JO - Environ Sci Technol VL - 52 IS - 21 N2 - The compound 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative to perfluorooctanesulfonate (PFOS) in the metal-plating industry, has been widely detected in various environmental matrices. However, its hepatotoxicity has yet to be clarified. Here, male mice were exposed to 0.04, 0.2, or 1 mg/kg/day of 6:2 Cl-PFESA for 56 days. Results demonstrated that relative liver weight increased significantly in the 0.2 and 1 mg/kg/day 6:2 Cl-PFESA groups, whereas liver lipid accumulation increased in all 6:2 Cl-PFESA groups. Serum enzyme activities of alanine transaminase and alkaline phosphatase were increased. Serum triglycerides and low-density lipoprotein cholesterol both increased, whereas serum total cholesterol and high-density lipoprotein cholesterol decreased following 6:2 Cl-PFESA exposure. A total of 264 differentially expressed proteins (127 up-regulated and 137 down-regulated), mainly involved in lipid metabolism, xenobiotic metabolism, and ribosome biogenesis, were identified by quantitative proteomics. Bioinformatics analysis highlighted the de-regulation of PPAR and PXR, which may contribute to the hepatotoxicity of 6:2 Cl-PFESA. Additionally, 6:2 Cl-PFESA induced both cell apoptosis and proliferation in the mouse liver. Compared to the overt toxicity of PFOS, 6:2 Cl-PFESA exhibited more-serious hepatotoxicity. Thus, caution should be exercised in the application of 6:2 Cl-PFESA as a replacement alternative to PFOS in industrial areas. SN - 1520-5851 UR - https://www.unboundmedicine.com/medline/citation/30256107/Subchronic_Hepatotoxicity_Effects_of_6:2_Chlorinated_Polyfluorinated_Ether_Sulfonate__6:2_Cl_PFESA__a_Novel_Perfluorooctanesulfonate__PFOS__Alternative_on_Adult_Male_Mice_ DB - PRIME DP - Unbound Medicine ER -