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EVALUATION OF PERFLUOROOCTANOIC ACID IMMUNOTOXICITY IN ADULT MICE.
Citation:
LUEBKE, R. W., C. B. COPELAND, AND J. DEWITT. EVALUATION OF PERFLUOROOCTANOIC ACID IMMUNOTOXICITY IN ADULT MICE. . Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
Perfluorooctanoic acid (PFOA) is used in the manufacture of fluoropolymers and may be formed by metabolism or degradation of other perfluoroalkyl acids. Safety concerns led the U.S. EPA to conduct a risk assessment of PFOA and related compounds due to their environmental persistence and serum levels of PFOA in the general population. Dietary exposure to PFOA was reported (Yang et al., 2000) to cause reversible thymic and splenic atrophy and suppression of the primary and secondary antibody responses to horse red blood cells in mice. The immunotoxic effects of PFOA were not observed in mice lacking the peroxisome proliferator-activated receptor α(PPAR α). Given the level of Agency concern and lack of corroborating studies, we evaluated the immunotoxicity of PFOA in adult mice. C57Bl/6J females were exposed to 30 mg/kg/d of PFOA (to approximate the daily dietary intake reported by Yang et al.) by gavage for 10 d. Mice were immunized with SRBC or sensitized to BSA on d11; a subgroup continued PFOA exposure (continuous, a total of 15 doses) and another subgroup of PFOA mice were switched to gavage with vehicle for an additional 5 exposures (recovery; 10 doses of PFOA, 5 of water). Body and spleen weights were decreased and liver weights were increased by constant exposure; body and spleen weights were similar in controls and the PFOA recovery group, but liver weights remained elevated in the recovery group. IgM responses were suppressed by constant PFOA exposure but were similar to control values in the recovery group. IgG responses were similar in all groups of mice boosted 2 weeks after primary immunization. Constant PFOA exposure was associated with a trend (p≈0.06) toward suppressed DTH responses. These data indicate that constant PFOA exposure suppresses humoral immunity and may adversely affect cell mediated immunity, but the effects are relatively short-lived. (This abstract does not reflect EPA policy.)