Pharmacokinetics of perfluorooctanoate in cynomolgus monkeys.
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 microg/ml in serum; 53, 166, and 181 microg/ml in urine; and, 7, 28, and 50 microg/g in feces. Mean liver concentrations reached 16, 14, and 50 microg/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.
Butenhoff
J L
JL
3M, St. Paul, Minnesota 55144, USA. jlbutenhoff@mmm.com
Kennedy
G L
GL
Hinderliter
P M
PM
Lieder
P H
PH
Jung
R
R
Hansen
K J
KJ
Gorman
G S
GS
Noker
P E
PE
Thomford
P J
PJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000493:pharmacokinetics*; D003627:Data Interpretation, Statistical; D005243:Feces / Q000737:chemistry; D005260:Female; D005466:Fluorocarbons / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008099:Liver / Q000737:chemistry; D008252:Macaca fascicularis; D008297:Male; D011786:Quality Control; D012015:Reference Standards
D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid