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HUMORAL AND CELL MEDIATED IMMUNE FUNCTION IN MICE EXPOSED TO PERFLUOROOCTANOIC ACID AS ADULTS
Citation:
LUEBKE, R. W., C. B. COPELAND, AND J. DEWITT. HUMORAL AND CELL MEDIATED IMMUNE FUNCTION IN MICE EXPOSED TO PERFLUOROOCTANOIC ACID AS ADULTS . Presented at Seminar, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MN, April 20, 2007.
Description:
Perfluorooctanoic acid (PFOA) is used in the manufacture of fluoropolymers, and may be formed by metabolism or degradation of other perfluoroalkyl acids and fluorotelomers. Safety concerns lead the U.S. EPA to conduct a risk assessment of PFOA and related compounds due to their environmental persistence and reports of serum levels of PFOA in the general population. Dietary exposure to PFOA was reported 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 female mice were exposed to a range of PFOA doses from 0.94 to 30 mg/kg/d of PFOA for 10-15 days. The highest dose was chosen to approximate the daily dietary intake previously reported to suppress antibody synthesis. The IgM response to sheep erythrocytes was suppressed by exposure to ¿3.75 mg/kg/d for 15 days, spanning the 10 days before and 5 days after immunization; contrary to a published report, exposure to 30 mg/kg/d for only the 10 days preceding immunization also suppressed the IgM response. Delayed type hypersensitivity responses to bovine serum albumin was not consistently altered by exposure. Evaluation of serum PFOA concentrations indicated that at the LOAEL (3.75 mg PFOA/kg/d for 15 days), the serum concentration was 7.5 X 104 ng/mL, or approximately one thousand fold greater than that in the general population of the US, and 500 hundred fold higher than a population that drank PFOA contaminated water near a PFOA production facility. However, median serum levels only 100 fold lower than the LOAEL have been reported in occupationally-exposed workers. Studies are currently in progress to evaluate immune system effects of PFOA exposure in mice lacking the alpha isoform of the peroxisome proliferator activated receptor, to determine whether effects are receptor mediated. Additional collaborative studies are in progress to determine whether PFOA is a developmental immunotoxicant.