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全氟丁酸在大鼠、小鼠、猴子和人类中的比较药代动力学及其与通过饮用水接触人类的相关性。

Comparative pharmacokinetics of perfluorobutyrate in rats, mice, monkeys, and humans and relevance to human exposure via drinking water.

作者信息

Chang Shu-Ching, Das Kaberi, Ehresman David J, Ellefson Mark E, Gorman Gregory S, Hart Jill A, Noker Patricia E, Tan Yu-Mei, Lieder Paul H, Lau Christopher, Olsen Geary W, Butenhoff John L

机构信息

Medical Department, 3M Company, St Paul, Minnesota 55144, USA.

出版信息

Toxicol Sci. 2008 Jul;104(1):40-53. doi: 10.1093/toxsci/kfn057. Epub 2008 Mar 18.

DOI:10.1093/toxsci/kfn057
PMID:18353799
Abstract

Perfluorobutyrate (PFBA) has been detected in precipitation, surface waters, water treatment effluent, and in public and private wells in Minnesota at up to low microg/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.

摘要

在明尼苏达州的降水、地表水、水处理废水以及公共和私人水井中,已检测到全氟丁酸(PFBA),其浓度高达低微克/升。我们评估了PFBA在大鼠、小鼠、猴子和人类中的药代动力学,为毒理学研究中的剂量选择提供合理依据,并协助进行人类健康风险评估。研究包括:(1)大鼠——静脉注射和口服;(2)小鼠——口服;(3)猴子——静脉注射;(4)人类——职业暴露志愿者。在血清(所有物种)、肝脏(大鼠和小鼠)、尿液(大鼠、小鼠和猴子)和粪便(大鼠和小鼠)中测定了PFBA。此外,我们对177名可能通过饮用水接触PFBA的个体的血清PFBA浓度进行了表征。男性(M)和女性(F)的平均血清PFBA终末消除半衰期(小时)分别为:(1)给大鼠30 mg/kg,口服时为9.22和1.76,静脉注射时为6.38和1.03;(2)给小鼠口服10、30或100 mg/kg全氟丁酸铵剂量,10 mg/kg时为13.34和2.87,30 mg/kg时为16.25和3.08,100 mg/kg时为5.22和2.79;(3)给猴子静脉注射10 mg/kg,为40.32和41.04;(4)人类为72.16和87.00(合并为74.63)。分布容积估计表明主要是细胞外分布。在可能通过饮用水接触PFBA的个体中,96%的血清PFBA浓度<2 ng/ml(最高6 ng/ml)。这些发现表明,PFBA能从血清中有效消除,重复接触时积累的可能性较低。

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