Immunotoxicity of Four Per- and Polyfluoroalkyl Substances Following 28-Day Oral Repeat Dosing in Rats Assessed by the Anti-Sheep Red Blood Cell IgM Response

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.