You are here:
Comparative Pharmacokinetics of Perfluorononanoic acid in Rats and Mice.
Citation:
TATUM, K. R., K. DAS, R. ZEHR, J. F. WAMBAUGH, M. STRYNAR, A. B. LINDSTROM, A. DELINSKY, AND C. LAU. Comparative Pharmacokinetics of Perfluorononanoic acid in Rats and Mice. Presented at Society of Environmental Toxicology and Chemistry (SETAC) meeting, New Orleans, LA, November 19 - 23, 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), a member of the perfluoroalkyl acids (PFAAs) is found at low concentrations in the environment, but detectable in humans and wildlife. Previous studies have examined the pharmacokinetics (PK) of shorter carbon-chain PFAAs, such as perfluorobutyric acid (PFBA) and perfluorooctanoic acid (PFOA) in humans as well as in animal models. However, at present, little is known about the PK profiles of PFNA except its rate of serum elimination in the rat. This study evaluated and compared the PK properties of PFNA in two laboratory animal models, the rat and the mouse. Male and female Sprague-Dawley rats were given a single dose ofPFNA by oral gavage at 1, 3, or 10 mg/kg, and blood was collected from the tail vein at timed intervals ranging from 1 to 50 days after treatment. At the terminal time point, liver and kidney were also harvested from each animal. Male and female CD-l mice were also given a single oral dose of PFNA at 1 or 10 mg/kg ana sacrificed at similar time points as the rat blood collections; and blood, kidney and liver samples were collected at each time point. Concentrations of PFNA were determined by LC-MS/MS. Serum elimination of PFNA was linear with exposure doses for both rodent species. In the rat, the rate' constant for elimination was significantly faster in females compared to males, which resulted in estimated serum halflives that were considerably different between the two sexes (t1/2 = 1.8 and 30.7 days for females and males, respectively). In the mouse, the rate constant for elimination was slightly faster in females than males, resulting in a serum half-life relatively comparable between the two sexes (t1/2 = 40.7 days for females and 64.4 days for males). 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 than PFBA and PFOA in the rodents; (2) PFNA is more persistent in the mouse than in the rat; (3) there is a major sex difference in the serum elimination of PFNA in the rat, but much less so in the mouse; and (4) there is a significantly higher accumulation of PFNA in the liver of male mice compared to females. This abstract does not necessarily reflect US. EPA policy