Grantee Research Project Results
2000 Progress Report: Biological Markers of Exposure to Benzene
EPA Grant Number: R826249Title: Biological Markers of Exposure to Benzene
Investigators:
Institution: Lovelace Biomedical & Environmental Research Institute
EPA Project Officer: Chung, Serena
Project Period: March 20, 1998 through March 19, 2001
Project Period Covered by this Report: March 20, 1999 through March 19, 2000
Project Amount: $471,696
RFA: Ambient Air Quality (1997) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Air
Objective:
The objective of this research project is to develop a panel of biological markers of exposure to benzene that can be used to relate the level of markers in the body in a quantitative manner to both recent and earlier exposures. The hypothesis is that by using a battery of benzene-specific biomarkers of varying half-lives in the body, one can more readily describe the type of exposure to benzene that has occurred in the past than with a single biomarker. For example, one should be able to distinguish between a person who has had a continuous low level of exposure to benzene (as in someone exposed to environmental tobacco smoke) from someone who has had a single high-level exposure to benzene in a hobby project. In the former case, one would expect to find a buildup of longer half-life markers and only a low level of shorter half-life markers, while in the latter case, one would detect high levels of short half-life markers and very little of the longer half-life markers. An empirically based mathematical model will be used to relate the current levels of biomarkers of varying half-lives to prior exposures to benzene. A variety of exposure regimens will be conducted in mice to determine if the markers can distinguish between the different regimens. Lastly, limited studies in petroleum workers will explore the usefulness of the battery of markers in assessing exposures in an occupational setting.Progress Summary:
The benzene-specific markers of exposure that were chosen were: urinary phenyl mercapturic acid (PMA) and t,t-muconic acid (relatively short half-lives), in addition to blood S-phenylcysteine adducts on albumin and hemoglobin (relatively long half-lives). Sensitive assays for all of the metabolites have been completed and soon will be published.A study to determine the half-lives of the four biomarkers was completed in male B6C3F1 mice exposed to 20, 200, or 600 ppm benzene for 4 hours. The half-lives determined in the study were used to develop an empirical mathematical model to be used to predict prior exposure based on multiple biomarkers of varying half-lives. The logic of the model is that equations describing the concentration-time relationships for multiple markers can be used to solve for the concentration and the time since exposure to benzene. A generalized negative exponential function has been fit to the data. The results suggest that the proposed empirical model will be capable of distinguishing between different time-concentration patterns of benzene exposure. Furthermore, because of the empirical basis of the underlying model structure, it may be easily extended to model different compounds.
A "mystery" exposure of mice to different levels of benzene was completed, and blood and urine samples were analyzed for the biomarkers of interest. These data were given blind (as to benzene exposure level and time since exposure) to the person who developed the model. Current work is focused on determining the ability of the model to predict prior benzene exposures.
Future Activities:
The biomarker data from the "mystery" exposure will be analyzed using the mathematical model to determine if the model can correctly determine the level of the prior exposure to benzene and the time since exposure.Journal Articles:
No journal articles submitted with this report: View all 7 publications for this projectSupplemental Keywords:
ambient air, exposure, toxics, mathematics, measurement methods, petroleum, benzene, toxicokinetics., Health, Scientific Discipline, Air, Toxics, air toxics, Environmental Chemistry, Health Risk Assessment, Epidemiology, HAPS, Risk Assessments, Biochemistry, Atmospheric Sciences, risk assessment, ambient air quality, monitoring, blood samples, animal model, air sampling, ambient monitoring, benzene, inhalation, human exposure, urine and blood samples, biocontaminants, half-life markers, biological markers, human health, Volatile Organic Compounds (VOCs), Benzene (including benzene from gasoline)Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.