Document Detail


Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.
MedLine Citation:
PMID:  14600279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.8 mg MTBE in 250 ml Gatorade(R), and inhaled 3.1 ppm. MTBE for 1 h. Blood and exhaled breath samples were then obtained. Blood MTBE peaked between 15 and 30 min following oral exposure, at the end of inhalation exposure, and ~5 min after dermal exposure. Elimination by each route was described well by a three-compartment model (Rsq >0.9). The Akaike Information Criterion for the three-compartment model was smaller than the two-compartment model, supporting it over the two-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured in blood slowly increased and plateaued, but it did not return to the pre-exposure baseline at the 24-h follow-up. TBA is very water-soluble and has a blood:air partition ratio of 462, reducing elimination by exhalation. Oral exposure resulted in a significantly greater MTBE metabolism into TBA than by other routes based on a greater blood TBA:MTBE AUC ratio, implying significant first-pass metabolism. The slower TBA elimination may make it a better biomarker of MTBE exposure, though one must consider the exposure route when estimating MTBE exposure from TBA because of first-pass metabolism. Most subjects had a baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can be used as a fuel additive, it is not a definitive marker of MTBE exposure. These data provide the risk assessment process of pharmacokinetic information relevant to the media through which most exposures occur-air and drinking water.
Authors:
James Prah; David Ashley; Benjamin Blount; Martin Case; Teresa Leavens; Joachim Pleil; Frederick Cardinali
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2003-11-04
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  77     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-12     Completed Date:  2004-10-12     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  195-205     Citation Subset:  IM    
Affiliation:
National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Caroline 27711, USA. prah.james@epa.gov
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MeSH Terms
Descriptor/Qualifier:
Administration, Cutaneous
Administration, Inhalation
Administration, Oral
Adult
Air Pollutants / pharmacokinetics*
Atmosphere Exposure Chambers
Biological Markers
Breath Tests
Drinking
Gasoline
Half-Life
Humans
Male
Methyl Ethers / blood,  pharmacokinetics*
Skin Absorption
Water
Water Pollutants, Chemical / pharmacokinetics*
Chemical
Reg. No./Substance:
0/Air Pollutants; 0/Biological Markers; 0/Gasoline; 0/Methyl Ethers; 0/Water Pollutants, Chemical; 1634-04-4/methyl tert-butyl ether; 7732-18-5/Water

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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