Adverse impacts of environmentally relevant PFOS alternatives on mice pancreatic tissues

Perfluorooctane sulfonate (PFOS) alternatives are chemicals that are used to make a range of products. Researchers have found that PFOS alternatives are probably no less toxic than PFOS, which has aroused concern. It has also revealed that the pancreas may be harmed by exposure to PFOS alternatives. However, there is insufficient evidence to demonstrate the toxicity mechanisms of PFOS alternatives. This study demonstrates the adverse effects of three PFOS alternatives on the pancreatic health of mice. After subchronic exposure to PFOS alternatives at environmentally relevant concentrations (800 μg/L perfluorohexanesulfonate, 800 μg/L perfluorobutanesulfonate, and 3 μg/L sodium ρ-perfluorous nonenoxybenzene sulfonate) via drinking water for 6 weeks, toxicity mechanisms were elucidated by examining histopathology, immunity, endoplasmic reticulum stress, 16S rRNA, and short-chain fatty acid targeted metabolomics. Sodium ρ-perfluorous nonenoxybenzene sulfonate significantly increased levels of TNF-α, IL-6, p-PERK, and ATF-4 and decreased the abundance of Akkermansia muciniphila and Lactobacillus reuteri. In addition, the three PFOS alternatives changed the composition of the gut microbiota in mice. Short-chain fatty acids, which are metabolites of the gut microbiota, also significantly decreased. Correlation analysis demonstrates that the alteration of gut microbes is related to the adverse effects on the mice pancreas. Results suggest that the murine pancreas may be toxic endpoints of PFOS alternatives. This study alerts the threats to human health and accelerates the toxicology research of an increasing number of emerging PFOS alternatives.