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Comparative Phamacokinetics of Perfluorobutyrate (Pfba) in Rats, Mice, Monkeys and Humans and Relevance to Human Exposure Via Drinking Water
Citation:
Chang, S., K. DAS, D. J. Ehresman, M. E. Ellefson, G. S. Gorman, J. A. Hart, P. E. Noker, Y. Tan, P. H. Lieder, C. LAU, G. W. Olsen, AND J. L. Butenhoff. Comparative Phamacokinetics of Perfluorobutyrate (Pfba) in Rats, Mice, Monkeys and Humans and Relevance to Human Exposure Via Drinking Water. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 104(1):40-53, (2008).
Impact/Purpose:
Perfluorobutyrate, a chemical manufactured by 3M in the past, has been detected in the surface water and drinking water wells at locations near the manufacturing plant and disposal sites in Minnesota. This discovery has drawn considerable interests from the State Health Department as well as concerns from the local residents. A major concern stems from the previous findings with perfluorooctanoic acid (PFOA), a chemical related to PFBA, where developmental and systemic toxicities in the laboratory animal models have been noted. The toxicity findings of PFOA are largely dependent on the animal species examined. For instance, the female rats are known to have a unique ability to clear the chemical efficiently (with half-life of 2 h, compared to the male counterparts with half-life of one week). This marked gender difference is absent in humans and primates, thereby rendering health risk assessment (using reproductive and developmental endpoints) difficult in species extrapolation. In contrast, no such sex difference regarding the clearance of PFOA was found in the mouse, but profound developmental toxicity in this species was indicated. Therefore, a clear understanding of the pharmacokinetic properties of the perfluorinated chemicals is prerequisite for their human health risk assessment. Toward that end, the current study compared the pharmacokinetic profiles of PFBA in various animal models, including rat, mouse and monkey, and these findings were discussed in reference to the biomonitoring evaluation of this chemical with production workers at 3M. In addition, the relevance of human exposure to PFBA via drinking water was addressed. These results will be instrumental to the risk assessment report being drafted by the Minnesota Health Department, under the mandate of the state legislature.
Description:
Perfluorobutyrate (PFBA) has been detected in precipitation, surface waters, water treatment effluent, and in public and private wells in Minnesota at up to low mug/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.
