Absorption, Distribution, Metabolism, and Elimination of 8-2 Fluorotelomer Alcohol in the Rat

化学 新陈代谢 尿 毒物动力学 葡萄糖醛酸 吸收(声学) 排泄 色谱法 药代动力学 粪便 间隙 分布(数学) 内分泌学 内科学 药理学 生物化学 生物 医学 物理 古生物学 数学分析 泌尿科 数学 声学
作者
William J. Fasano,Stephen Carpenter,Shawn A. Gannon,Timothy Arthur Chandos Snow,Judith C. Stadler,Gerald L. Kennedy,Robert C. Buck,Stephen H. Korzeniowski,Paul M. Hinderliter,Raymond A. Kemper
出处
期刊:Toxicological Sciences [Oxford University Press]
卷期号:91 (2): 341-355 被引量:129
标识
DOI:10.1093/toxsci/kfj160
摘要

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 (∼ 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.
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