Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein

Archives of Toxicology volume 92, pages359–369(2018)Cite this article

Abstract

Although shorter chain homologues and other types of fluorinated chemicals are currently used as alternatives to long-chain perfluoroalkyl substances (PFASs), their safety information remains unclear and urgently needed. Here, the cytotoxicity of several fluorinated alternatives (i.e., 6:2 fluorotelomer carboxylic acid (6:2 FTCA), 6:2 fluorotelomer sulfonic acid (6:2 FTSA), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), and hexafluoropropylene oxide (HFPO) homologues) to human liver HL-7702 cell line were measured and compared with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their binding mode and affinity to human liver fatty acid binding protein (hL-FABP) were also determined. Compared with PFOA and PFOS, 6:2 Cl-PFESA, HFPO trimer acid (HFPO-TA), HFPO tetramer acid (HFPO-TeA), and 6:2 FTSA showed greater toxic effects on cell viabilities. At low exposure doses, these alternatives induced cell proliferation with similar mechanism which was different from that of PFOA and PFOS. Furthermore, binding affinity to hL-FABP decreased in the order of 6:2 FTCA < 6:2 FTSA < HFPO dimer acid (HFPO-DA) < PFOA < PFOS/6:2 Cl-PFESA/HFPO-TA. Due to their distinctive structure, 6:2 Cl-PFESA and HFPO homologues were bound to the hL-FABP inner pocket with unique binding modes and higher binding energy compared with PFOA and PFOS. This research enhances our understanding of the toxicity of PFAS alternatives during usage and provides useful evidence for the development of new alternatives.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21737004, 31320103915 and 21377128) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB14040202).

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Affiliations

  1. Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China

    Nan Sheng, Ruina Cui, Jianshe Wang & Jiayin Dai

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Nan Sheng

  3. Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Jinghua Wang

  4. Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People’s Republic of China

    Yong Guo

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  1. Nan Sheng
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Correspondence to Jiayin Dai.

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Sheng, N., Cui, R., Wang, J. et al. Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein. Arch Toxicol 92, 359–369 (2018). https://doi.org/10.1007/s00204-017-2055-1

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Keywords

  • Novel fluorinated alternatives
  • Cytotoxicity
  • HL7702 cell lines
  • Protein binding
  • hL-FABP