13-week dietary toxicity study of ammonium perfluorooctanoate (APFO) in male rats.

Ammonium perfluorooctanoate is a perfluorinated carboxylate that is used commercially as a processing aid in the production of fluorinated polymers. Perfluorooctanoate (PFOA) has been found in human blood of the general population from exogenous sources. This report presents the results of a 13-week dietary toxicity study in male rats and was designed to identify potential target organ(s), dose response, and to explore possible relationships of PPARalpha activation to potential liver effects and hormonal changes. Rats were fed dietary levels of 0, 1, 10, 30, and 100 ppm (equivalent to 0, 0.06, 0.64, 1.94, and 6.5 mg/kg/day) for 13 weeks. A control group pair-fed adjusted to the 100 ppm level and groups allowed to recover for 8 weeks were included. Sacrifices were conducted after 4, 7, and 13 weeks of feeding and after 8 weeks of recovery. At each sacrifice, gross and histopathology was conducted on selected tissues and measurements of hepatic palmitoyl CoA oxidase (PCoAO), as well as serum estradiol, luteinizing hormone, testosterone, and PFOA were determined. There were no clinical signs or mortality. Body weight gains were reduced in the 100 ppm dose group. Liver weights (absolute and relative), PCoAO activity, and hepatocyte hypertrophy (minimal to mild) were increased in the 10 ppm dose group and above and were reversible in recovery. Under the study conditions, hormone levels appeared unchanged. PFOA serum concentrations increased in a dose-related fashion, appeared to reach steady-state by test week 5, and declined rapidly through the recovery period. Serum PFOA concentrations at the end of the treatment period were 7.1, 41, 70, and 138 microg/mL in the 1, 10, 30 and 100 ppm dose groups. The study no effect level was 1 ppm (0.06 microg/mg) with doses of 10 ppm (0.64 microg/mg) and higher producing adaptive and reversible liver changes.