Citation:

PLEIL, J. D., D. KIM, J. D. PRAH, D. ASHLEY, AND S. RAPPAPORT. THE UNIQUE VALUE OF BREATH BIOMARKERS FOR ESTIMATING PHARMACOKINETIC RATE CONSTANTS AND BODY BURDEN FROM ENVIRONMENTAL EXPOSURES. Chapter 24, Anton Amann and David Smith (ed.), Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. World Scientific Publishing Co. Pte. Ltd., 5 Toh Tuck Link, Singapore, , 347-359, (2005).

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:

Although detection of breath odor is the oldest of the medical diagnostic techniques, blood and urine biomarker measurements are the current "gold standard" for modern exposure and health assessments. Of late, it has been recognized that collecting exhaled breath is an attractive alternative to blood and urine sampling because it is less invasive and is not restricted by sample volume or time frame. In this work, we use a simple classical pharmacokinetic (PK) model and explore the utility of breath measurement for assessing uptake, metabolism, and elimination of an exogenous chemical. We demonstrate the unique value of breath biomarkers as a complementary measurement to blood biomarkers using results from previous study of controlled human exposures to methyl tertiary butyl ether (MTBE) and the production of the primary first order metabolite tertiary butyl alcohol (TBA). We estimate initial 72% alveolar uptake efficiency from inhalation exposure of MTBE and a steady state conversion of 68% of MTBE body burden to TBA corresponding to 0.385/hr and 0.818/hr rate constants, respectively. Only 0.53% of TBA body burden is eliminated via breath, the remainder is excreted or metabolized with a rate constant of 0.0565/hr. We further demonstrate that the temporal concentration profiles of breath and blood biomarkers are similar in character and that they result in consistent estimates of average dose from external sources. We estimate steady-state blood/breath ratios for MTBE and TBA as 16.9 and 797 and hypothetical volumes of distribution as 86 l and 175 l, respectively. Finally, we attribute to pulmonary metabolism about 0.8% of MTBE to TBA conversion from inhalation exposure.

The United States Environmental Protection Agency through its Office of Research and Development funded the research described here. It has been subjected to Agency review and approved for publication.

Record Details: