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PHARMACOKINETIC EVALUATION OF PERFLUOROOCTANOIC ACID IN THE MOUSE
Citation:
Lau, C S., M J. Strynar, A B. Lindstrom, R. G. Hanson, J R. Thibodeaux, AND H Barton. PHARMACOKINETIC EVALUATION OF PERFLUOROOCTANOIC ACID IN THE MOUSE. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Pharmacokinetic evaluation of perfluorooctanoic acid in the mouse.
1C. Lau, 2M.J. Strynar, 2A.B. Lindstrom, 1R.G. Hanson, 1J.R. Thibodeaux and 3H.A. Barton.
1Reproductive Toxicology Division, 3Experimental Toxicology Division, NHEERL, 2Human Exposure and Atmospheric Sciences Division, NERL, ORD, U.S. EPA, RTP, NC
Perfluorooctanoic acid (PFOA) is a stable chemical surfactant with wide industrial and consumer applications.Because PFOA has been detected in both human and wildlife populations,its potential adverse health effects are under active investigation. The pharmacokinetic properties of PFOA are unique: in the rat, there is a pronounced gender difference in its renal clearance such that half-life in females is estimated as 3 h and that in males as 5 days; however, such a major gender difference is absent in humans. The present study is designed to examine the pharmacokinetic properties inanother rodent species. Young male and female CD-1 mice received a single gavage administration of PFOA at either 1 or 10 mg/kg. Three animals from each group were sacrificed at 4h, 8h, 12h, or 1, 3, 6, 9, 13, 20, 27, 34, 42, 48 days after treatment. Serum was prepared from trunk blood collected from the descending aorta and analyzed for PFOA by HPLC-MS-MS. PFOA was absorbed readily, reaching Cmax between 4-8 h. In contrast to the rat, no discernable gender difference in the disposition of PFOA was observed in the mouse. The terminal serum half-life of PFOA was estimated in the range of 15-20 days. A similar pharmacokinetic profile was seen in both dose groups, suggesting linearity between body burden of the fluorochemical and administered doses up to 10 mg/kg. These results thus indicate a significant difference in the pharmacokinetic disposition of PFOA between the rat and the mouse, with the profile of the latter species resembling thelack of an apparent sex-dependent elimination in humans. This abstract does not necessarily reflect U.S. EPA policy.