Hexafluoropropylene oxide trimer acid (HFPO-TA), a recently developed substitute for perfluorooctanoic acid (PFOA), has seen extensive application but has also led to widespread contamination of water bodies. Nevertheless, its toxicological impact on commercially important fish species remains poorly understood. In this study, hook snout carp Opsariichthys bidens were exposed to aqueous solutions of PFOA and HFPO-TA for 60 days. Subsequent analyses focused on histopathological changes, enzymatic activity alterations, and gene expression profiles within the intestinal tissues of O. bidens . Findings revealed that both PFOA and HFPO-TA exposures triggered oxidative stress, DNA damage, cellular apoptosis, and disruptions in intestinal barrier function, digestion, immunity, and energy metabolism. Notably, HFPO-TA specifically impacted oxidative stress pathways, apoptosis rates, intestinal structural integrity, immune responses, and mitochondrial function. Integrated biomarker response (IBR) analysis further demonstrated that HFPO-TA exerted a more pronounced toxic effect on the guts compared to PFOA, underscoring the greater severity of harm posed by this alternative PFAS to O. bidens . These results emphasized that substituting legacy PFAS compounds with newer alternatives did not guarantee reduced toxic side effects. Despite advances in understanding the toxicological profiles of both legacy and emerging PFAS compounds, our current grasp of the full environmental burden posed by these persistent pollutants remains severely limited, likely representing only the surface of a much larger problem. Continued investigation into alternative PFAS is imperative to fully elucidate their environmental fate and to disrupt the ongoing cycle of "pollution-replacement-repollution". • HFPO-TA induces significantly more severe intestinal toxicity than legacy PFOA. • Both PFASs disrupt TJ proteins, impair DNA repair, and alter apoptosis activity. • HFPO-TA causes pronounced intestinal structural and mitochondrial damage than PFOA. • HFPO-TA presents higher side-effects and may be a regrettable replacement for PFOA.
Wu et al. (Sun,) studied this question.