Hexafluoropropylene oxide trimer acid is an unsafe substitute to perfluorooctanoic acid: The perspectives of intestinal microflora and hepatotoxicity in frog.

As a substitute for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) exhibits similar chemical structure to PFOA. However, its effects on hepatointestinal injury in aquatic organism and its comparative organ-specific toxicity relative to PFOA remain incompletely understood. In this study, male black-spotted frogs were exposed to HFPO-TA at environmentally relevant concentrations (1 and 10 μg/L) and an extreme concentration (100 μg/L) for 21 days, followed by comprehensive analyses. Significant alterations in the gut microbial composition and the content of intestinal barrier proteins (occludin, ZO-1, and ZO-2 level), accompanied by elevated levels of lipopolysaccharide (LPS) and its binding protein (LBP) were observed in the intestine of frog exposed to HFPO-TA. In the liver, HFPO-TA induced oxidative stress, promoted the expression of pro-inflammatory cytokines, and caused histopathological damage. Correlation analysis further suggested that HFPO-TA-mediated intestinal toxicity and increased serum LPS levels may be associated with liver injury. Additionally, comparative assessments of the toxic potency of HFPO-TA and PFOA revealed that, although HFPO-TA is less toxic than PFOA, it can still exhibit toxic effects at environmentally relevant concentrations. This research reveals that HFPO-TA may be not a safe alternative to PFOA and provides new insights into its toxicological mechanisms in amphibians.