BackgroundPerfluorooctanoic acid (PFOA), an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose.ObjectiveThe aim of this study was to evaluate PFOA effects on humoral and cellular immunity using standard assays for assessing immune function, and to derive dose–response data.MethodsC57BL/6J mice received 0 or 30 mg PFOA/kg/day for 10 days; half of the exposed groups were switched to vehicle and half continued on PFOA for five days. C57BL/6N mice received 0–30 mg/kg/day of PFOA in drinking water for 15 days. Mice were immunized with sheep red blood cells or sensitized to bovine serum albumin in Freund’s complete adjuvant on day 10 of exposure; immune responses were determined 1 day post-exposure.ResultsWe found that 30 mg PFOA/kg/day given for 10 or 15 days reduced IgM synthesis; serum collected 1 day postexposure contained 8.4 × 104 or 2.7 × 105 ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures ≥ 3.75 mg PFOA/kg/day in a dose-dependent manner, and IgG titers were elevated at 3.75 and 7.5 mg PFOA/kg/day. Serum PFOA at 3.75 mg/kg/day was 7.4 × 104 ng/mL 1 day postexposure, or 150-fold greater than the levels reported in individuals living near a PFOA production site. Using a second-degree polynomial model, we calculated a benchmark dose of 3 mg/kg/day, with a lower bound (95% confidence limit) of 1.75 mg/kg/day. Cell-mediated function was not affected.ConclusionsIgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations.

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The T-cell-dependent antibody response is suppressed in mice exposed to 3.75, 7.5, 15, and 30 mg PFOA (perfluorooctanoic acid)/kg body weight (bw). Reduced bw accompanied immunosuppression at 15 and 30 mg/kg. We investigated the hypothesis that the observed immunosuppression is secondary to elevated serum corticosterone levels by assessing immune function in adrenalectomized (adx) or sham-operated C57BL/6N female mice exposed to 0, 7.5, or 15 mg PFOA/kg bw in drinking water for 10 days. Bw, primary antibody responses to a T-dependent antigen, clinical serum chemistries related to liver health, and serum corticosterone levels were evaluated. Exposure to 15 mg/kg decreased bw by approximately 10% after 8 days of dosing and until 2 days postdosing in both adx and sham animals; bw of adx animals were still reduced 5 days postdosing. IgM antibody titers were statistically reduced by 15% in sham animals and 18% in adx animals exposed to 15 mg/kg and by 11.8% in adx animals exposed to 7.5 mg/kg. Corticosterone concentrations were elevated by 157% in dosed sham animals relative to control animals and were reduced by 27% in dosed adx animals relative to control animals (neither changes were statistically significant). Clinical serum chemistries related to liver health were not statistically altered by either dose or adrenalectomy. The failure of adrenalectomy to protect mice from the immunosuppressive effects of PFOA indicates that suppression of antibody synthesis is not the result of liver toxicity or stress-related corticosterone production.