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DOSE-RESPONSE OF PERFLUOROOCTANOIC ACID-INDUCED IMMUNOMODULATION IN ADULT C57BL/6 MICE
Citation:
DEWITT, J., C. B. COPELAND, AND R. W. LUEBKE. DOSE-RESPONSE OF PERFLUOROOCTANOIC ACID-INDUCED IMMUNOMODULATION IN ADULT C57BL/6 MICE. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Perfluorooctanoic acid (PFOA), used in fluoropolymer production, is environmentally persistent, present in the human population worldwide, and is associated with myriad health effects under laboratory conditions. A preliminary risk assessment by the US EPA identified immunosuppression as an endpoint of concern, citing reports of splenic and thymic atrophy and reduced antibody synthesis in adult mice fed 30 mg PFOA/kg body weight (BW) for 15d (Yang et al., 2000, 2001, 2002). However, the level of Agency concern and lack of corroborating studies warranted a more thorough dose-response assessment. C57BL/6 female mice were given 0, 3.75, 7.5, 15, or 30 mg PFOA/kg BW via drinking water for 15d. Mice were immunized with SRBC or sensitized to BSA on d11 of dosing, serum was collected for evaluation of IgM titers 1d post-dosing (PD), mice were challenged with BSA 3d PD, and footpad swelling measured 4d PD. Booster immunizations with SRBC were given 10d PD and serum was collected 15d PD for evaluation of IgG titers. IgM titers were suppressed at all doses of PFOA; IgG titers were suppressed by 30 mg/kg, but elevated at lower doses, suggesting recovery and rebound. DTH responses were suppressed by 7.5 and 15 mg PFOA/kg. Body, spleen and thymus weights were decreased and liver weights increased 1d PD by 15 and 30 mg/kg. By 15d PD, body, spleen and thymus weights were normalizing but liver weights remained elevated. These data indicate that 15d of PFOA exposure suppresses humoral immunity, but that function recovers within 15d after exposure at doses below 30 mg PFOA/kg, which is consistent with the recovery of spleen and thymus weights. DTH responses are suppressed by exposure to PFOA, but appears less sensitive than humoral responses. Although we failed to find a NOAEL for the immune functions evaluated, our LOAEL for IgM titers (3.75 mg PFOA/kg) was nearly 10-fold lower than the 30 mg PFOA/kg reported by Yang et al. (2002). This abstract does not reflect EPA policy and was supported by UNC/EPA Cooperative Training Agreement CT829472.