ToxSci Advance Access originally published online on October 6, 2004
Toxicological Sciences 2004 82(2):394-406; doi:10.1093/toxsci/kfh302
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Toxicological Sciences vol. 82 no. 2 © Society of Toxicology 2004; all rights reserved.
Pharmacokinetics of Perfluorooctanoate in Cynomolgus Monkeys
* 3M, St. Paul, Minnesota 55144; DuPont Haskell Laboratory, Newark, Delaware 19714; Clariant, Sulzbach D-65840, Germany; Southern Research Institute, Birmingham, Alabama 35205 and ¶ Covance, Madison, Wisconsin 53704
Received May 21, 2004; accepted September 7, 2004
The pharmacokinetics of perfluorooctanoate (PFOA) in cynomolgus monkeys were studied in a six-month oral capsule dosing study of ammonium perfluorooctanoate (APFO) and in a single-dose iv study. In the oral study, samples of serum, urine, and feces were collected every two weeks from monkeys given daily doses of either 0, 3, 10, or 20 mg APFO/kg. Steady-state was reached within four weeks in serum, urine, and feces. Serum PFOA followed first-order elimination kinetics after the last dose, with a half-life of approximately 20 days. Urine was the primary elimination route. Mean serum PFOA concentrations at steady state in the 3, 10, and 20 mg/kg-day dose groups, respectively, were 81, 99, and 156 µg/ml in serum; 53, 166, and 181 µg/ml in urine; and, 7, 28, and 50 µg/g in feces. Mean liver concentrations reached 16, 14, and 50 µg/g in the 3, 10, and 20 mg/kg groups, respectively. In the iv study, three monkeys per sex were given a single dose of 10 mg/kg potassium PFOA. Samples were collected through 123 days. The terminal half-life of PFOA in serum was 13.6, 13.7, and 35.3 days in the three male monkeys and 26.8, 29.3, and 41.7 days in the three females. Volume of distribution at steady state was 181 ± 12 and 198 ± 69 ml/kg for males and females, respectively. Based on the result of both the oral and iv studies, the elimination half-life is approximately 14–42 days, and urine is the primary route of excretion.
Key Words: perfluorooctanoate; PFOA; pharmacokinetics; monkey; APFO.
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