ToxSci Advance Access published online on March 18, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn057
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Comparative Pharmacokinetics of Perfluorobutyrate (PFBA) in Rats, Mice, Monkeys, and Humans and Relevance to Human Exposure via Drinking Water
* Medical Department, 3M Company, St. Paul, MN 55144, United States
United States Environmental Protection Agency, Reproductive Toxicology Division, Research Triangle Park, NC 27711, United States
Environmental Laboratory, 3M Company, St. Paul, MN 55144, United States
Southern Research Institute, Birmingham, AL 35205, United States
¶ The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, United States
1 Corresponding author: John L. Butenhoff, 3M Company, Medical Department, 3M Center 220-06-W-08, St. Paul, MN 55144, United States; Telephone 651-733-1962; fax 651-733-1773; e-mail jlbutenhoff{at}mmm.com
Received January 18, 2008; revision received March 12, 2008; accepted March 13, 2008
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Abstract |
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Perfluorobutyrate (PFBA) has been detected in precipitation, surface waters, water treatment effluent, and in public and private wells in Minnesota at up to low µg/L concentrations. We evaluated the pharmacokinetics of PFBA in rats, mice, monkeys, and humans to provide a rational basis for dose selection in toxicological studies and to aid in human health-risk assessment. Studies included: (1) rats - iv and oral; (2) mice – oral; (3) monkeys - iv; and (4) humans - occupationally exposed volunteers. PFBA was determined in serum (all species), liver (rats and mice), urine (rats, mice, and monkeys), and feces (rats and mice). In addition, we characterized serum PFBA concentrations in 177 individuals with potential exposure to PFBA through drinking water. Mean terminal serum PFBA elimination half-lives for males (M) and females (F), respectively, in h were: 1) for rats given 30 mg/kg, 9.22 and 1.76 (oral), and 6.38 and 1.03 (iv); 2) for mice given oral doses of 10, 30, or 100 mg/kg ammonium PFBA, 13.34 and 2.87 at 10 mg/kg, 16.25 and 3.08 at 30 mg/kg; and 5.22 and 2.79 at 100 mg/kg; 3) for monkeys given 10 mg/kg iv, 40.32 and 41.04; and 4) for humans, 72.16 and 87.00 (74.63 combined). Volume of distribution estimates indicated primarily extracellular distribution. Among individuals with plausible exposure via drinking water, 96 % of serum PFBA concentrations were < 2 ng/mL (maximum 6 ng/mL). These findings demonstrate that PFBA is eliminated efficiently from serum with a low potential for accumulation from repeated exposure.
Key Words: Perfluorobutyrate; PFBA; pharmacokinetics; biomonitoring.
E-mail addresses: John L. Butenhoff, jlbutenhoff{at}mmm.com; Shu-Ching Chang, s.chang{at}mmm.com; Kaberi Das, das.kaberi{at}epa.gov; David J. Ehresman, djehresman{at}mmm.com; Mark E. Ellefson, meellefson{at}mmm.com; Gregory S. Gorman, Gorman{at}sri.org; Jill A. Hart, jahart{at}mmm.com; Christopher Lau, lau.christopher{at}epa.gov; Paul H. Lieder, phlieder1{at}mmm.com; Patricia E. Noker, noker{at}sri.org; Geary W. Olsen, gwolsen{at}mmm.com; Yu-Mei Tan, ctan{at}thehamner.org
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