Systemic and immunotoxicity induced by topical application of perfluorohexane sulfonic acid (PFHxS) in a murine model

Per- and polyfluoroalkyl substances (PFAS) are a large group of stable man-mad surfactants that are incorporated into numerous products for their water and oil resistance and have been associated with adverse health effects. The present study evaluated the systemic and immunotoxicity of sub-chronic 28- or 10-day dermal exposure of PFHxS (0.625-5% or 15.63-125 mg/kg/dose) in a murine model. Elevated levels of PFHxS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. Liver weight (% body) significantly increased and spleen weight (% body) significantly deceased with PFHxS exposure supported by histopathological changes. Additionally, PFHxS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen with genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells, NK cells, and CD11b+ cells in the spleen along with increases in CD4+ and CD8+ T-cells, NK cells, and neutrophils in the skin. These findings support dermal PFHxS-induced liver damage and immune suppression. These data support PFHxS absorption through the skin and demonstrate immunotoxicity via this exposure route, raising concern about prompting the need for further investigation.