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大鼠体内8-2氟调聚物醇的吸收、分布、代谢及排泄

Absorption, distribution, metabolism, and elimination of 8-2 fluorotelomer alcohol in the rat.

作者信息

Fasano William J, Carpenter Stephen C, Gannon Shawn A, Snow Timothy A, Stadler Judith C, Kennedy Gerald L, Buck Robert C, Korzeniowski Stephen H, Hinderliter Paul M, Kemper Raymond A

机构信息

DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714, USA.

出版信息

Toxicol Sci. 2006 Jun;91(2):341-55. doi: 10.1093/toxsci/kfj160. Epub 2006 Mar 16.

DOI:10.1093/toxsci/kfj160
PMID:16543293
Abstract

The absorption, distribution, metabolism, and elimination of [3-14C] 8-2 fluorotelomer alcohol (8-2 FTOH, C7F1514CF2CH2CH2OH) following a single oral dose at 5 and 125 mg/kg in male and female rats have been determined. Following oral dosing, the maximum concentration of 8-2 FTOH in plasma occurred by 1 h postdose and cleared rapidly with a half-life of less than 5 h. The internal dose to 8-2 FTOH, as measured by area under the concentration-time curve to infinity, was similar for male and female rats and was observed to increase in a dose-dependent fashion. The majority of the 14C 8-2 FTOH (> 70%) was excreted in feces, and 37-55% was identified as parent. Less than 4% of the administered dose was excreted in urine, which contained low concentrations of perfluorooctanoate (approximately 1% of total 14C). Metabolites identified in bile were principally composed of glucuronide and glutathione conjugates, and perfluorohexanoate was identified in excreta and plasma, demonstrating the metabolism of the parent FTOH by sequential removal of multiple CF2 groups. At 7 days postdose, 4-7% of the administered radioactivity was present in tissues, and for the majority, 14C concentrations were greater than whole blood with the highest concentration in fat, liver, thyroid, and adrenals. Distribution and excretion of a single 125-mg/kg [3-14C] 8-2 FTOH dermal dose following a 6-h exposure in rats was also determined. The majority of the dermal dose either volatilized from the skin (37%) or was removed by washing (29%). Following a 6-h dermal exposure and a 7-day collection period, excretion of total radioactivity via urine (< 0.1%) and feces (< 0.2%) was minor, and radioactivity concentrations in most tissues were below the limit of detection. Systemic availability of 8-2 FTOH following dermal exposure was negligible.

摘要

已测定雄性和雌性大鼠单次口服剂量为5和125mg/kg的[3-14C] 8-2氟调聚物醇(8-2 FTOH,C7F1514CF2CH2CH2OH)后的吸收、分布、代谢和排泄情况。口服给药后,血浆中8-2 FTOH的最大浓度在给药后1小时出现,并迅速清除,半衰期小于5小时。以浓度-时间曲线下面积至无穷大衡量的8-2 FTOH体内剂量,雄性和雌性大鼠相似,且呈剂量依赖性增加。大部分14C 8-2 FTOH(>70%)经粪便排泄,37-55%被鉴定为母体。给药剂量中不到4%经尿液排泄,尿液中全氟辛酸浓度较低(约占总14C的1%)。胆汁中鉴定出的代谢物主要由葡糖醛酸和谷胱甘肽结合物组成,排泄物和血浆中鉴定出全氟己酸,表明母体FTOH通过依次去除多个CF2基团进行代谢。给药后7天,给药放射性的4-7%存在于组织中,大多数情况下,14C浓度高于全血,脂肪、肝脏、甲状腺和肾上腺中的浓度最高。还测定了大鼠经6小时暴露后单次125mg/kg [3-14C] 8-2 FTOH皮肤剂量的分布和排泄情况。大部分皮肤剂量要么从皮肤挥发(37%),要么通过清洗去除(29%)。经6小时皮肤暴露和7天收集期后,经尿液(<0.1%)和粪便(<0.2%)排泄的总放射性很少,大多数组织中的放射性浓度低于检测限。皮肤暴露后8-2 FTOH的全身可用性可忽略不计。

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