Comparing single and repeated dosimetry data for perfluorooctane sulfonate in rats

Perfluorooctane sulfonate (PFOS) is a member of a class of perfluorinated chemicals used in a variety of consumer and industrial applications because of their oleophobic and hydrophobic properties. It has been shown to cause toxicity in adult and developing laboratory animals. Because PFOS has also been shown to be widely distributed throughout the environment, there have been concerns about its potential health risk to humans. Limited pharmacokinetic data for PFOS are available in rodents and humans, while epidemiological studies of workers and extensive toxicity studies in rodents have been performed. The existing pharmacokinetic and toxicity database in rodents can be useful in the cross-species extrapolations needed to evaluate and interpret internal dosimetry in humans. A mathematical model that describes the disposition of PFOS in adult rats following intravenous, oral, and chronic dietary exposures was developed to gain a better understanding of the pharmacokinetics of PFOS and to determine whether single-dose kinetics are predictive of repeated-dose kinetics. In order to characterize existing time-course data, time-dependent and concentration-dependent changes in the pharmacokinetic parameters for urinary and biliary clearance and liver distribution were needed. Whether these time-dependent changes represent inconsistencies across experiments, effects of aging in the rats, or chemically induced changes in pharmacokinetics remains to be determined.