You are here:
Comparative Pharmacokinetics of Perfluorononanoic acid in Rats and Mice*.
Citation:
Tatum-Gibbs, K., K. P. 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 EPA/PFAA Days III Meeting, Research Triangle Park, NC, June 08 - 10, 2010.
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 is also detectable in humans and wildlife. Previous studies have examined the pharmacokinetics (PK) of lower 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 animals, the rat and the mouse. Male and female Sprague-Dawley rats (n = 3) were given a single treatment of PFNA by oral gavage at 1, 3, or 10 mg/kg, and blood was collected from the tail vein at time 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 (n = 4) were given a single oral dose of PFNA at 1 or 10 mg/kg, sacrificed at similar time intervals as the rats, and trunk blood, liver, and kidney samples were collected at each time point. Serum, liver, and kidney concentrations of PFNA were determined by HPLCMS-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 female rats compared to male rats (Kelim = 0.010/h for females and 0.0014/h for males), which resulted in estimated serum half-lives that were considerably different between the two genders (t l/2 = 30.7 and 1.8 days for males and females, respectively). In the mouse, the rate constant for elimination was slightly faster in females than males (Kelim = 0.0011/h for females and 0.0007/h for males), resulting in a serum half-life relatively comparable between the two sexes (t 1/2 = 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 PFOA and PFBA 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 than that in the females. This abstract does not necessarily reflect u.s. EPA policy.