Toxicology 281 (2011) 48–55 Contents lists available at ScienceDirect Toxicology journal homepage: www.elsevier.com/locate/toxicol Comparative pharmacokinetics of perfluorononanoic acid in rat and mouse  Katoria Tatum-Gibbs a , John F. Wambaugh b , Kaberi P. Das c , Robert D. Zehr c , Mark J. Strynar d , Andrew B. Lindstrom d , Amy Delinsky d , Christopher Lau c,∗ a Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, United States b National Center for Computational Toxicology, Research Triangle Park, NC, United States c Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC, United States d Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States article info Article history: Received 3 November 2010 Received in revised form 20 December 2010 Accepted 5 January 2011 Available online 13 January 2011 Keywords: Perfluorononanoic acid Pharmacokinetics Mouse Rat abstract Perfluorononanoic acid (PFNA) is a fluorinated organic chemical found at low levels in the environment, but is detectable in humans and wildlife. The present study compared the pharmacokinetic properties of PFNA in two laboratory rodent species. Male and female Sprague–Dawley rats were given a single dose of PFNA by oral gavage at 1, 3, or 10 mg/kg, and blood was collected from the tail vein at 1, 2, 3, 4, 7, 16, 21, 28, 35, 42 and 50 days after treatment. In addition, livers and kidneys were collected for PFNA analysis at the terminal time point. CD-1 mice were given a single oral dose of PFNA of 1 or 10 mg/kg, and 4 males and 4 females were killed at similar time intervals; trunk blood, liver and kidney were collected. Serum and tissue concentrations of PFNA were determined by LC–MS/MS. Serum elimination of PFNA is by and large linear with exposure doses in the rat; however, like PFOA, a major sex difference in the rate of elimination is observed, with an estimated half-life of 30.6 days for males and 1.4 days for females. PFNA is stored preferentially in the liver but not in the kidneys. In the mouse, the rates of PFNA serum elimination are non-linear with exposure dose and are slightly faster in females than males, with terminal estimated serum half-life of 25.8–68.4 days and 34.3–68.9 days, respectively. PFNA is also stored preferentially in the mouse liver but not in the kidneys. Hepatic uptake appears to be more efficient and storage capacity greater in male mice than in females. These data 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 hepatic accumulation of PFNA in male mice than in females. Published by Elsevier Ireland Ltd. 1. Introduction Perfluoroalkyl acids (PFAAs) and their derivatives are a family of synthetic organic compounds that have been widely used in a variety of consumer and industrial applications for over half a century (Renner, 2001). Their strong surfactant properties make them ideal water and oil repellents, lubricants, as well as pro- cessing aides in the manufacture of fluoropolymers. PFAAs are composed of a carbon backbone, generally ranging from C-4 to C-14, with a complete substitution of hydrogen with fluorine, and contain a functional group usually carboxylate, sulfonate or  The information in this document has been funded by the U.S. Environmental Protection Agency. ∗ Corresponding author at: Mail Drop 67, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Tel.: +1 919 541 5097; fax: +919 541 4017. E-mail address: lau.christopher@epa.gov (C. Lau). phosphonate. These chemicals are extremely stable, practically non-biodegradable and persistent in the environment (Lau et al., 2007; Prevedouros et al., 2006). In recent years, these fluoro- chemicals have become a focus of public health concern due to their ubiquitous presence in environmental media (air, water, soil, sediment and house dust), food and drinking water, their global distribution, and their widespread presence in wild-life and humans (Calafat et al., 2007a; Chang et al., 2008; Davis et al., 2007; Houde et al., 2006b; Lau et al., 2007; Powley et al., 2008). In light of the on-going production and continuous release of PFAAs into the environment, research has been conducted to evaluate their potential adverse health and environmental impacts. In particular, the toxicological profiles of the 8-carbon PFAAs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been extensively examined in laboratory animal mod- els (Andersen et al., 2008; Giesy et al., 2010; Lau et al., 2007), partly due to their high volumes of production, their abundance in the environment, and their prevalence in human and wildlife 0300-483X/$ – see front matter. Published by Elsevier Ireland Ltd. doi:10.1016/j.tox.2011.01.003