Hepatotoxic Effects of Hexafluoropropylene Oxide Trimer Acid (HFPO-TA), A Novel Perfluorooctanoic Acid (PFOA) Alternative, on Mice

As
an alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene
oxide trimer acid (HFPO-TA) has been increasingly used for fluoropolymer
manufacture in recent years. Its growing detection in environmental
matrices and wildlife raises considerable concern about its potential
health risks. Here we investigated the effects of HFPO-TA on mouse
liver following 28 days of exposure to 0.02, 0.1, or 0.5 mg/kg/d of
HFPO-TA via oral gavage. Results showed that HFPO-TA concentrations
increased to 1.14, 4.48, and 30.8 μg/mL in serum and 12.0, 32.2,
and 100 μg/g in liver, respectively. Liver injury, including
hepatomegaly, necrosis, and increase in alanine aminotransferase activity,
was observed. Furthermore, total cholesterol and triglycerides decreased
in the liver in a dose-dependent manner. Liver transcriptome analysis
revealed that 281, 1001, and 2491 genes were differentially expressed
(fold change ≥2 and FDR < 0.05) in the three treated groups,
respectively, compared with the control group. KEGG enrichment analysis
highlighted the PPAR and chemical carcinogenesis pathways in all three
treatment groups. Protein levels of genes involved in carcinogenesis,
such as AFP, p21, Sirt1 C-MYC, and PCNA, were significantly increased.
Compared with previously published toxicological data of PFOA, HFPO-TA
showed higher bioaccumulation potential and more serious hepatotoxicity.
Taken together, HFPO-TA does not appear to be a safer alternative
to PFOA.