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 focuses on biomarkers of benzene exposure to better understand the complex human metabolism of this ubiquitous environmental carcinogen. A host of biomarkers are being applied in studies of benzene-exposed populations and controls. These biomarkers include protein adducts of several toxic metabolites of benzene, of benzene in breath and urine, and of benzene metabolites in urine. Using these biomarkers, Dr. Rappaport's team is evaluating the uptake and metabolism of benzene over a wide range of human exposures. Human biomarkers are measured in samples of blood, urine, and breath obtained in prior studies and by collaborators at other institutions. Benzene metabolites of interest include reactive intermediates such as benzene oxide (BO) and 1,2- and 1,4-benzoquinone (BQ), as well as the following stable urinary products: phenol, catechol, hydroquinone, trihydroxybenzene, E,E-muconic acid (MA) and S-phenylmercapturic acid (SPMA).
Project investigators measured benzene in air, breath and urine of 340 active-duty personnel in the U.S. Air Force, who had been assigned a priori into exposure categories for jet fuel (JP-8). They also measured albumin adducts of benzene oxide (BO-Alb) and 1,2- and 1,4-BQ (1,2- and 1,4-BQ-Alb) in 269 benzene-exposed workers and 140 control workers from Tianjin, China and in 190 control subjects from Chapel Hill, N.C. balanced by race (black and white), gender, and smoking status. A new analytical method for benzene metabolites was applied in urine samples collected from the Tianjin, China cohort.
Dr. Rappaport's team substantially increased their pool of data with which to model the production of biologically reactive metabolites of benzene. They have now measured albumin adducts in about 1000 subjects exposed to benzene over the range of 0 – 320 ppm. These data will permit exploration of the saturable metabolism of benzene as well as the kinetics of adduct production and elimination in humans.