Superfund Research Program
Development and Application of Biomarkers of Exposure
Project Leader: Stephen M. Rappaport (University of California-Berkeley)
Grant Number: P42ES005948
Funding Period: 1995 - 2011
This project is developing and applying biomarkers of exposure to benzene, a known human carcinogen and ubiquitous environmental contaminant. The following biomarkers are included: unmetabolized benzene in exhaled air and urine, urinary benzene metabolites, and blood protein adducts of electrophilic metabolites of benzene. The overall goal is to understand the relationship between environmental exposure and the levels of these biomarkers among persons exposed to benzene. Project investigators have produced evidence that benzene oxide (BO) is produced by metabolism of benzene in the liver and kidney but not in the bone marrow of rats dosed with benzene. Since benzene causes bone marrow toxicity, this suggests that BO must be distributed to the bone marrow via the blood after production in other tissues. Researchers have also shown that adducts of BO with the blood proteins hemoglobin (Hb) and albumin (Alb) are stable in vivo, while adducts of 1,4-benzoquinone, another electrophilic metabolite of benzene, exhibit moderate to great chemical instability in vivo. This has implications to the use of the various adducts as biomarkers of exposure to benzene. It also motivated development of a kinetic model that allows blood levels of both stable and unstable Hb adducts to be related to the blood dose of an electrophilic species. Finally, a self-administered test kit was used to investigate the relationship between exposure and breath levels of benzene during automobile refueling. Results showed that benzene in breath was highly correlated with benzene exposure during short periods of refueling (3 min. median duration).