ToxSci Advance Access originally published online on March 16, 2006
Toxicological Sciences 2006 91(2):341-355; doi:10.1093/toxsci/kfj160
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Absorption, Distribution, Metabolism, and Elimination of 8-2 Fluorotelomer Alcohol in the Rat
* DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714; DuPont Chemical Solutions Enterprise, Wilmington, Delaware 19880; Battelle Pacific Northwest, Richland, Washington 99352; and Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877
Received January 15, 2006; accepted March 3, 2006
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.
Key Words: 8-2 fluorotelomer alcohol; absorption, distribution, metabolism, and elimination (ADME); glutathione conjugates; perfluorinated carboxylic acids; perfluorooctanoate; peroxisome proliferation; pharmacokinetics.
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