Archives of Toxicology

, Volume 92, Issue 1, pp 359–369 | Cite as

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

  • Nan Sheng
  • Ruina Cui
  • Jinghua Wang
  • Yong Guo
  • Jianshe Wang
  • Jiayin DaiEmail author
In vitro systems


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.


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



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).

Supplementary material

204_2017_2055_MOESM1_ESM.docx (157 kb)
Supplementary material 1 (DOCX 157 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Nan Sheng
    • 1
    • 2
  • Ruina Cui
    • 1
  • Jinghua Wang
    • 3
  • Yong Guo
    • 4
  • Jianshe Wang
    • 1
  • Jiayin Dai
    • 1
    Email author
  1. 1.Key Laboratory of Animal Ecology and Conservation Biology, Institute of ZoologyChinese Academy of SciencesBeijingPeople’s Republic of China
  2. 2.University of Chinese Academy of SciencesBeijingChina
  3. 3.Research Center of Environmental ScienceZhejiang University of TechnologyHangzhouPeople’s Republic of China
  4. 4.Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiPeople’s Republic of China

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