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PHARMACOKINETIC PROFILES OF PERFLUOROOCTANOIC ACID IN MICE AFTER CHRONIC EXPOSURE
Citation:
DAS, K., Z. Dan, M. STRYNAR, A. B. LINDSTROM, J. F. WAMBAUGH, AND C. LAU. PHARMACOKINETIC PROFILES OF PERFLUOROOCTANOIC ACID IN MICE AFTER CHRONIC EXPOSURE. Presented at Society of Toxicology 49th annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
In the current study, accumulation of PFOA in serum and liver was evaluated after repeated treatment at various doses
Description:
Perfluorooctanoic acid (PFOA) is highly persistent in humans, with serum half-life estimates of 2.3 to 3.8 years. In the mouse, elimination of PFOA appears to be first-order after a single oral administration, with serum half-life estimates of 16 days for females and 22 days for males. In the current study, accumulation of PFOA in serum and liver was evaluated after repeated treatment at various doses. Young adult female CD-1 mice were given PFOA once daily by oral gavage at 0.1, 1, or 10 mg/kg. For each time point examined at intervals of several days during a 3 week period, three mice from each dose group were sacrificed 24 h after the last treatment. Serum and liver samples were collected for PFOA determination by HPLC-MS-MS. Dose-dependent elevations of liver weight were seen in the 1 and 10 mg/kg groups, but not at 0.1 mg/kg. At 0.1 mg/kg, serum concentrations of PFOA increased linearly with treatment duration, and the concentrations of PFOA in liver appeared to mirror those of serum (ratio concentrations serum:liver 1:1). At 1 mg/kg, serum concentrations of PFOA also increased with treatment duration, but levels of the chemical in liver were about twice as high as those in serum. At 10 mg/kg, PFOA concentrations rose rapidly both in the serum and liver, but appeared to reach steady-state levels after one week of repeated exposure; however, levels of PFOA in liver were about twice of serum levels after 3 weeks (similar to the 1 mg/kg group). The enhanced accumulation of PFOA in the mouse liver correlated well with increases of liver weight (r² = 0.98). These results suggest that serum and liver accumulation of PFOA and elimination kinetics are dependent on exposure doses, likely involving saturation of hepatic and renal transporters at the high doses. This abstract does not necessarily reflect US EPA policy.