Toxicokinetics of perfluoroalkyl carboxylic acids with different carbon chain lengths in mice and humans.

OBJECTIVES: Perfluoroalkyl carboxylic acids (PFCAs) consist of analogs with various carbon chain lengths. Their toxicokinetics have remained unexplored except in the case of perfluorooctanoic acid (8 carbon chemicals). This study aimed to investigate the toxicokinetics of PFCAs with six to fourteen carbon atoms (C6 to C14) in mice and humans.

METHODS: We applied a two-compartment model to mice administered PFCAs intravenously or by gavage. The time courses of the serum concentration and tissue distribution and elimination were evaluated for 24 hours after treatment. For human samples, urine from healthy volunteers, bile from patients who underwent biliary drainage, and cerebral spinal fluid (CSF) from brain drainage were collected.

RESULTS: The mouse experiment showed that short-chained PFCAs (C6 and C7) were rapidly eliminated in the urine, whereas long-chain PFCAs (C8 to C14) accumulated in the liver and were excreted slowly in feces. Urinary clearance of PFCAs in humans also decreased with increasing alkyl chain lengths, while biliary clearances increased. C9 to C10 had the smallest total clearance for both mice and humans. However, disparities existed in the magnitude of the total clearance between mice and humans. A slightly higher partition ratio (brain/serum) was observed for long-chained PFCAs in mice, but this was not observed in the corresponding partition ratio in humans (CSF/serum).

CONCLUSIONS: The large sequestration volumes of PFCAs in the liver seem to be attributable to the liver's large binding capacity in both species. This will be useful in evaluating PFCA bioaccumulation in other species.