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
Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous environmental contaminants that are present in most waste sites on the National Priorities List identified by the Environmental Protection Agency. These chemicals are also in air, water, and food throughout the world. Although epidemiologic studies have shown that PAH exposures are associated with cancers, exposure-response relationships are unclear due to the lack of quantitative exposure data for the hundreds of individual PAH compounds emanating from a particular source.
Dr. Stephen Rappaport’s research group is developing and applying biomarkers of exposure to PAHs to better quantify exposures of PAHs in humans. A host of biomarkers is being applied, including protein adducts of reactive intermediates of PAH metabolism, unmetabolized PAHs in urine, and PAH metabolites in urine. These biomarkers are being measured in several hundred specimens of blood and urine collected from persons exposed to PAHs in various environments, namely, coke and steel factories, the trucking industry, the asphalt industry, and homes where coal is used for fuel. Using state-of-the-art mass spectrometry, the group has developed assays to measure protein adducts of PAHs, unmetabolized PAHs in urine, and urinary metabolites of PAHs, with extremely high sensitivity and specificity. These methods will facilitate the quantitation of PAH exposures in epidemiology studies of health effects. For example, current work indicates that levels of unmetabolized naphthalene and phenanthrene, two of the simplest PAHs, are good measures of exposures to PAHs from diesel exhaust, asphalt emissions, and steel production. The researchers have also identified hydroxylated metabolites of phenanthrene as useful biomarkers of exposure to PAHs. This suggests that measurements of these urinary biomarkers can be used to estimate total PAH exposures in human studies.
Their work with biomarkers indicating 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 PAHs.