| Perfluorooctanoic Acid–Induced Immunomodulation in Adult C57BL/6J or C57BL/6N Female Mice Jamie C. DeWitt,1 Carey B. Copeland,2 Mark J. Strynar,3 and Robert W. Luebke2 1Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 2Immunotoxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, and 3National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA Abstract
Background: Perfluorooctanoic acid (PFOA) , an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose. Objective: The 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. Methods: C57BL/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. Results: We 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. Conclusions: IgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations. Key words: fluorinated compounds, immunomodulation, immunotoxicity, perfluoroalkyl acids, PFOA. Environ Health Perspect 116:644–650 (2008) . doi:10.1289/ehp.10896 available via http://dx.doi.org/ [Online 7 February 2008]
Address correspondence to R. Luebke, U.S. Environmental Protection Agency, MD B143-01, 109 TW Alexander Dr., Research Triangle Park, NC 27711 USA. Telephone: (919) 541-3672. Fax: (919) 541-3538. E-mail: luebke.robert@epa.gov We thank D. Andrews, J. Bradshaw, and W. Williams for technical assistance, and A. Howard for assistance with interpretation of benchmark doses. L. Birnbaum, D. Germolec, S. Fenton, and M. Selgrade reviewed the manuscript and provided helpful suggestions. Partial support was provided by UNC/EPA Cooperative Training Agreement CT829472. This report has been reviewed by the U.S. Environmental Protection Agency's Office of Research and Development, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 18 September 2007 ; accepted 6 Febuary 2008.
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