Publications : 2025

Hughes MF, DeVito MJ, Patlewicz G, Thomas RS, Adams LD, Ambroso JL, Yang X, Upadhyay BG, et al. 2025. Immunotoxicity of four per- and polyfluoroalkyl substances following 28-day oral repeat dosing in rats assessed by the anti-sheep red blood IgM response. Toxics 13(6):490; doi: 10.3390/toxics13060490. PMID: 40559963.

Abstract

Some PFASs are immunotoxic in rodent models and associated with diminished vaccine response in exposed humans. This study assessed the immunotoxicity of four PFASs via the T cell-dependent IgM antibody response (TDAR) to sheep red blood cells (SRBCs) in adult male rats following 28-day oral repeat dosing. The PFASs included 1H,1H,9H-perfluorononyl acrylate (PFNAC), 1H,1H,2H,2H-perfluorohexyl iodide (PFHI), 2-chlorotetrafluoropropionic acid (CTFPA), and 3,3,4,4,5,5,5-heptafluoropentan-2-one (MHFPK), administered in corn oil. The positive control was cyclophosphamide (CPS). Rats were dosed with vehicle or PFAS from Days 0 to 27. On Day 22, an immunogenic dose of SRBCs was administered intravenously. Positive control animals were administered CPS by intraperitoneal injection from Days 22-27. On Day 28, the animals were euthanized; blood, thymus, and spleen samples were collected and weighed. Serum IgM was quantified by enzyme-linked immunosorbent assay. Body weights were unaffected in PFAS-treated rats, except for 3 and 10 mg/kg/day PFNAC-treated rats on Days 24, 27, and 28. Relative spleen and thymus weights and serum IgM levels were not affected by the PFASs at the doses tested, whereas CPS-treated animals had significant decreases in these parameters. The rat TDAR, as assessed by the anti-SRBC IgM response, was not affected by these four PFAS test agents following a 28-day oral exposure.