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Comparative Pharmacokinetics of Perfluorononanoic acid in Rats and Mice
Citation:
TATUM, K. R., K. DAS, R. ZEHR, C. LAU, M. J. STRYNAR, A. B. LINDSTROM, AND J. F. WAMBAUGH. Comparative Pharmacokinetics of Perfluorononanoic acid in Rats and Mice. Presented at 2009 Society of Toxicity Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
Perfluroalkyl acids (PFAAs) and their derivatives are organic compounds that have been widely used in industry. Perfluorononanoic acid (PFNA) is apart of the PFAA family and has been found at low levels in the environment, but is detectable in humans and wildlife. The purpose of this research is to evaluate the pharmacokinetic properties associated with perfluorononanoic acid (PFNA) using rat and mouse models.
Description:
Perfluorononanoic acid (PFNA) is a fluorinated organic chemical found at low levels in the environment, but is detectable in humans and wildlife. This study compared the pharmacokinetic properties of PFNA in two laboratory rodent species. Male and female Sprague-Dawley rats (n = 3) were given PFNA by oral gavage at 1, 3, or 10 mg/kg, and blood was collected from tail vein at 1, 2, 3, 4, 7, 16, 21, 28, 35, 42 and 50 days after treatment. CD-1 mice were given a single oral dose of PFNA at 1 or 10 mg/kg, and 4 males and 4 females were sacrificed at similar time intervals; trunk blood and liver were collected. Serum and liver concentrations of PFNA were determined by HPLC-MS-MS. Serum elimination of PFNA was linear with exposure doses in both species. In the rat, half-lives of 24 and 3.8 days were estimated for males and females, respectively. In the mouse, serum disappearance of PFNA was biphasic. The initial distribution phase of the chemical was significantly faster in the males than in the females (Vd = 0.0231 1/h for males and 0.141 1/h for females), although the subsequent elimination phase appeared to be similar between the two sexes (t½ = 58 days for males and 41 days for females). Correspondingly, the appearance of PFNA in the liver was faster, and the chemical reached higher levels in the male mice than in the females. These data thus suggest that (1) PFNA is more persistent in the mouse than in the rat; (2) there is a major sex difference in the serum elimination of PFNA in the rat, but much less so in the mouse; and (3) there is a significantly higher accumulation of PFNA in the liver of male mice than that in the females. This abstract does not necessarily reflect U.S. EPA policy.