Are developmentally exposed C57BL/6 mice insensitive to suppression of TDAR by PFOA?

Abstract

Perfluorooctanoic acid (PFOA) is an environmentally persistent fluorinated compound that is present in biological samples worldwide and associated with multisystem toxicity in laboratory animal models. Several studies have reported suppression of T-cell-dependent antibody responses (TDAR) in adult rodent models after 15 or 28 days of exposure. A related compound, perfluorooctane sulfonate (PFOS), was reported to suppress TDAR in developmentally exposed mice. The developmental effects of PFOA exposure on TDAR have not been explored; therefore, the objective of our study was to determine if TDAR suppression would occur in developmentally exposed mice. Pregnant C57BL/6 mice were given 0, 0.5, or 1 mg PFOA/kg body weight (BW) in drinking water from gestation day (GD) 6 to GD17. At postnatal day (PND) 2, litters/dam were reduced to three males and three females. On PND21, female offspring were weaned and separated and on PND43, they were intravenously immunized with sheep red blood cells. Serum for evaluation of IgM titers and PFOA concentrations was collected 5 days later. Booster immunizations were given 14 days later; serum for evaluation of IgG titers and PFOA concentrations was collected 5 days later. Litter weights were statistically decreased by 10% in the 1 mg/kg group relative to controls, but liver weights, lymphoid organ weights, and TDAR did not differ in female offspring by dose. Mean PFOA serum concentrations were 122 ng/mL (0.5 mg/kg) and 183 ng/mL (1 mg/kg) and <1 ng/mL for controls. PFOA serum concentrations in offspring were 400-fold lower than serum concentrations reported to suppress TDAR in adults; however, mice exposed during development did not survive doses higher than 1 mg/kg. Therefore, although TDAR in adult mice is sensitive to PFOA exposure, the doses and exposure scenario of this study did not induce developmental immunotoxicity (DIT). C57BL/6 mice are likely more sensitive to the overt developmental toxicity of PFOA than to potential DIT.