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
Benzene is an ubiquitous environmental contaminant that is emitted from most waste sites on the National Priorities List identified by the Environmental Protection Agency. This chemical is also widely used industrially in the U.S. and throughout the world. Although past investigations have shown that benzene causes leukemia and aplastic anemia in highly-exposed workers, potential effects of environmental exposure to benzene at much lower levels have been controversial. This controversy has been accentuated because, although metabolism is thought to be required for benzene to exert its toxicity, the metabolism of benzene has hardly been explored in humans. This lack of key information prompted investigators of the Development and Application of Biomarkers of Exposure project to develop and apply biomarkers of exposure to elucidate the metabolic pathways in humans exposed to benzene over a wide range of air levels. A host of biomarkers has been applied, including protein adducts of several reactive metabolites of benzene, of benzene in breath and urine, and of benzene metabolites in urine. These biomarkers have been measured in over 1000 benzene-exposed workers and controls in numerous studies, as part of collaborations with investigators at the SBRP of the University of California, Berkeley, at the National Cancer Institute (NCI), and at New York University. These studies have led to important findings regarding the potential for benzene to cause toxic effects at low levels of exposure. Measurements of both urinary benzene metabolites and protein adducts of reactive benzene metabolites by the Development and Application of Biomarkers of Exposure project have shown that the metabolism of benzene becomes saturated at levels of exposure much lower than had been previously thought. This suggests that persons exposed to low environmental levels efficiently metabolize benzene and, therefore, receive proportionally greater doses of toxic metabolites than workers exposed to much higher levels. Project investigators' results also indicate that the effects of metabolizing genes and gene-environment interactions upon benzene metabolite levels are rather small when compared to the large effects of benzene exposure per se upon metabolism. This work with biomarkers of exposure, coupled with complementary studies involving biomarkers of effect and susceptibility by collaborators at the University of California SBRP and at the National Cancer Institute have important implications for the assessment of risks among persons exposed to low levels of benzene.