ToxSci Advance Access published online on November 4, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfh009
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, MD 58B, Research Triangle Park, NC 27711
* To whom correspondence should be addressed. E-mail: prah.james{at}epa.gov.
Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 µg/ml MTBE dermally in tap water for one hr, drank 2.8 mg MTBE in 250 ml Gatorade®, and inhaled 3.1 ppm MTBE for one hr. Blood and exhaled breath samples were obtained. Blood MTBE peaked between 15-30 min following oral exposure, at the end of inhalation exposure, and
© 2003 Society of Toxicology
Biotransformation and Toxicokinetics
Dermal, Oral, and Inhalation Pharmacokinetics of Methyl Tertiary Butyl Ether (MTBE) in Human Volunteers
2 Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341
3 National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Abstract 
5 min after dermal exposure. Elimination by each route was described well by a 3-compartment model (Rsq > 0.9). The Akaike Information Criterion for the 3-compartment model was smaller than the 2-compartment model supporting it over the 2-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured in blood slowly increased, plateaued, but did not return to pre-exposure baseline at the 24 hr 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 exposure route when estimating MTBE exposure from TBA because of first pass metabolism. Most subjects had baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can be used as a fuel additive, TBA is not a definitive marker of MTBE exposure. These data provide the risk assessment process pharmacokinetic information relevant to the media through which most exposures occur - air and drinking water.
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