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A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR METHYL TERTIARY BUTYL ETHER (MTBE): A REVIEW OF EXISTING MODELS
Citation:
BLANCATO, J. N., M. V. EVANS, A. TSANG, AND FRED W. POWER. A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR METHYL TERTIARY BUTYL ETHER (MTBE): A REVIEW OF EXISTING MODELS. Presented at 2006 Annual Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Impact/Purpose:
MTBE is a volatile organic compound used as an oxygenate additive to gasoline, added to comply with the 1990 Clean Air Act. Previous PBPK models for MTBE were reviewed and incorporated into EPA’s present model designed using the Exposure Related Dose Estimating Model (ERDEM) software. EPA’s model also included an explicit pulmonary compartment. Organs (compartments) included in the model were: liver (for metabolism), fat, kidney, brain, and slowly and rapidly perfused compartments. Both inhalation and oral dosing were included as routes of exposure. Numerous simulations were performed to compare performance between present and previous MTBE PBPK models with available data : (400 and 8000 ppm inhalation exposure for 6 hours, and oral dosing of 40 and 400 mg/kg to a 215g rat). Physiological and Metabolic parameters were changed to human values and model performance was re-examined. Using available human data (inhalation, dermal and oral exposures), model comparisons were matched to MTBE peak values, MTBE area under the curve, and peak concentration for the metabolite TBA.
Description:
In summary, a revised EPA PBPK model for MTBE has been tested against previous models and across different species.