Research Program Area: Health & Exposure
Topic Areas: Mobile Sources & Fuels
The effect of gasoline concentration on the dermal absorption and fate of 14C-methanol in methanol/gasoline fuel mixtures was studied. A total of 120 adult Sprague-Dawley rats were treated on the intact skin with 100% methanol or one of five methanol/gasoline mixtures containing 95, 90, 85, 50 or 5% methanol. Immediately following dermal application of the methanol/gasoline mixtures, the rats were placed individually in all-glass, flow-through metabolism cages. During the post-treatment period, exhaled and evaporated methanol vapors, exhaled carbon dioxide, and excreta were collected. The animals were sacrificed at intervals following exposure and the 14C-content of excreta, blood and major tissues was determined. The data were used to determine the fraction of applied methanol absorbed for each fuel mixture, to assess the fate and distribution of dermally-applied methanol, and to develop a physiologically-based pharmacokinetic (PBPK) model of methanol disposition in the rat. The mean dermal absorption efficiency of methanol from the methanol/gasoline fuel mixtures was 24.8, 31.6, 24.5, 27.0, 35.7 and 58.1% for 100, 95, 90, 85, 50 and 5% methanol mixtures, respectively. However, only the fuel mixtures containing 5% and 50% methanol showed statistically significant enhancement of dermal absorption efficiency relative to 100% methanol. One explanation for this enhancement is the increasingly non-polar nature of the methanol/gasoline mixture as the proportion of gasoline in the mixture increases. At very high gasoline concentrations the increased hydrophobic interactions between the non-polar gasoline components act to force the very polar methanol out of the vehicle and into the stratum corneum of the skin. Another possible explanation is a skin damaging effect of gasoline, which may enhance methanol absorption. Also, simple dilution of the methanol with gasoline would tend to reduce the methanol evaporation rate (and the amount of methanol absorbed) by reducing the methanol partial pressure gradient between the skin surface and the bulk air. A large percentage (mean of 68%) of the dermally applied methanol evaporated within 60 minutes for all mixtures studied. With the possible exception of the kidney, there was no elevated concentration of 14C-methanol equivalents in any tissue relative to plasma concentrations during the 24-hour post-treatment period. At 24 hours post-treatment, the main elimination route of absorbed 14C-methanol was via metabolism to carbon dioxide (about 50%). An additional 1-5% was eliminated via exhalation as methanol and about 4-11% was eliminated as uncharacterized 14C-compounds in the excreta. The remaining portion of absorbed 14C-methanol (30-40%) remained in the body. A PBPK model successfully simulated the main aspects of methanol absorption and disposition as observed in this study.
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