Perfluorooctanoic acid-induced immunomodulation in adult C57BL/6J or C57BL/6N female mice.
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 x 10(4) or 2.7 x 10(5) ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures > or = 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 x 10(4) 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.
Dewitt
Jamie C
JC
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Copeland
Carey B
CB
Strynar
Mark J
MJ
Luebke
Robert W
RW
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D002210:Caprylates / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL
D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D007155:Immunologic Factors; C023036:perfluorooctanoic acid