You are here:
PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER
Citation:
Leavens, T L., D. L. Ashley, J. D. Pleil, M W. Case, AND J D. Prah. PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER. Presented at Society of Toxiocology (SOT), San Francisco, CA, March 25-29, 2001.
Description:
Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether (MTBE), an oxygenated fuel additive, from contaminated water sources. The purpose of this research was to develop a physiologically based pharmacokinetic model describing in humans the disposition of MTBE and the metabolite tertiary butyl alcohol (TBA) from inhalation, oral, and dermal exposures. Compartments in the model included alveolar space, arterial and venous blood, brain, fat, gastrointestinal tract, kidney, liver, rapidly perfused tissues, sampled and arms, and slowly perfused tissues. To accurately simulate the clinical human exposure and sampling conditions, the exposed arm and sampled arm were described by subcompartments for arterial blood, upper arm tissue, forearm tissue, forearm skin, antecubetal venous blood, and venous blood. Metabolism of MTBE and TBA was assumed to occur only in the liver, and elimination was assumed to occur via exhalation of MTBE and TBA and urinary elimination of TBA. Dermal absorption was described by Fick's law, and oral absorption was described as first order for the bioavailable dose. Initial estimates for parameters were obtained from the literature. Assuming that the physiological and biochemical parameters did not vary among the three routes of exposure, final estimates for parameters in the model were obtained by comparing the model with data for blood and alveolar breath concentrations of MTBE and TBA in male subjects who were exposed by inhalation, ingestion, or skin absorption. The model with the optimized parameters accurately simulated pharmacokinetics of MTBE and TBA in humans for all three routes. Of the inhaled, oral, and dermal doses 54, 47, and 54%, respectively, were exhaled as MTBE, and 44, 52, and 44%, respectively, were metabolized to TBA. This model can be used to simulate environmental exposure to MTBE. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy).