Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice

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.