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EXPOSURE RECONSTRUCTION FOR REDUCING UNCERTAINTY IN RISK ASSESSMENT: EXAMPLE USING MTBE BIOMARKERS AND SIMPLE PHARMACOKINETIC MODEL
Citation:
PLEIL, J. D., D. KIM, J. D. PRAH, AND S. M. RAPPAPORT. EXPOSURE RECONSTRUCTION FOR REDUCING UNCERTAINTY IN RISK ASSESSMENT: EXAMPLE USING MTBE BIOMARKERS AND SIMPLE PHARMACOKINETIC MODEL. BIOMARKERS. Taylor & Francis, Inc., Philadelphia, PA, 12(4):331-348, (2006).
Impact/Purpose:
The objective of this task is to develop state-of-the-art methods for measuring xenobiotic compounds, to include the isolation of the analyte from the appropriate matrix (extraction), preconcentration (typically sorbent-based), and analysis via GC/MS and/or LC/MS. Once established, these methods will be applied in small scale pilot studies or demonstration projects. Particular emphasis will be placed on methods which are readily transferable to other laboratories, including those within the Human Exposure and Atmospheric Sciences Division (HEASD), the National Exposure Research Laboratory (NERL), other EPA Laboratories, Program Offices, Regions, and academic institutions.
Specific objectives of this task include the following:
1) Development of GC/MS and LC/MS methods for the measurement of key xenobiotic compounds and their metabolites (to include the pyrethroid pesticides, perfluorinated organic compounds, and the BFRs) in relevant environmental and biological matrices.
2) Development of efficient low cost methods for the extraction and clean up of these compounds collected from relevant matrices.
3) Determination of xenobiotic compound and metabolite concentrations in samples derived from laboratory and field monitoring studies to help assess exposures and evaluate associated risks.
Description:
Adverse health risks from environmental agents are generally related to average (long term) exposures. We used results from a series of controlled human exposure tests and classical first order rate kinetics calculations to estimate how well spot measurements of methyl tertiary butyl ether (MTBE) and the primary metabolite, tertiary-butyl alcohol (TBA), can be expected to predict different hypothetical scenarios of previous exposures. We concluded that individual biomarker measurements are a valuable tool in reconstruction of previous exposures and that a simple pharmacokinetic model can limit the time frames over which a particular exposure - biomarker pair of compounds is useful.