Comparative Immunotoxicity and Transcriptomic Profiling of Seven PFAS in THP-1 Macrophages

While legacy PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have been extensively studied and linked to immunotoxicity, far less is known about the immune-related hazards of newer-generation alternatives. In this study, we systematically evaluated the immunotoxic potential of seven PFAS, including three perfluoroalkyl acids (PFOA, PFOS, PFHpS) and four (poly-)ether PFAS (PFESA BP2, PFESA BP1, DOPFLCA, 8:2 Cl-PFESA) using a THP-1 macrophage model with dose-range exposures for up to 72 hours.

Despite an equipotent dosing scheme, the molecular responses to different PFAS congeners were distinct. RNA sequencing revealed that PFOA and PFHpS, but not PFOS, elicited a larger number of differentially expressed genes than ether PFAS. We observed that the absolute PFAS concentration correlated more strongly with the number of DEGs than viability-based potency, suggesting differences in the underlying mechanisms of toxicity.