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VALIDATION AND EVALUATION OF BIOMARKERS IN WORKERS EXPOSED TO BENZENE IN CHINA
Impact/Purpose:
Human exposure to benzene is widespread because it is a component of gasoline and is also used extensively as an industrial solvent. Exposure to high levels of benzene is associated with development of leukemia and other blood disorders, but the risks of exposure to low levels of benzene are not well understood. In the 1990s the Health Effects Institute initiated a research program designed to study the effects of exposure to toxic air pollutants at ambient levels. As one part of this research program, HEI’s Request for Applications (RFA) 93-1 supported studies to develop reliable and sensitive assays for biomarkers of benzene exposure—both recent and longer-term—and of benzene effect. The biomarkers of recent exposure were urinary metabolites (measuring responses up to hours after exposure) and adducts of blood proteins (days to weeks after exposure). The biomarkers of longer-term exposure were chromosomal changes, integrating exposure over months to years. Because chromosomal changes may be determinants of subsequent health effects, they may also be considered early biomarkers of benzene effect. Chromosomal changes may also be due to causes other than exposure to benzene.
To validate the biomarkers characterized in these studies, another part of the research program, Request for Qualifications (RFQ) 95-3, “Transitional Epidemiology Studies for Benzene or 1,3-Butadiene Biomarkers,” solicited applications from investigators with access to suitable human populations exposed to benzene or butadiene. HEI funded a study by Dr Qingshan Qu of New York University School of Medicine to evaluate putative biomarkers in workers occupationally exposed to benzene in China.
Description:
Qu and colleagues recruited 181 healthy workers in several factories in the Tianjin region of China. These subjects formed part of a cohort of thousands identified by the U.S. National Cancer Institute (NCI) and the China Academy of Preventive Medicine for a study to evaluate tumor incidence in benzene exposed workers (NCI/China study). In phase 1 of their study, Qu and colleagues evaluated the suitability of using urinary metabolites, blood adducts, or chromosomal aberrations in polymorphonuclear leukocytes and lymphocytes as benzene biomarkers in 25 heavily exposed and 25 unexposed workers. The urinary metabolites measured were phenol, catechol, hydroquinone, benzene triol, S-phenylmercapturic acid (S-PMA), and trans,trans-muconic acid (t,t-MA). The blood adducts measured were benzene oxide and benzoquinone adducts of albumin.
In phase 2, the investigators used biomarkers validated in phase 1 of the study to evaluate relations between benzene exposures and levels of these biomarkers in another 105 benzene-exposed workers and 26 unexposed workers. The investigators focused on obtaining samples from workers whose current day exposures to benzene were no more than 5 ppm, representing the low end of occupational exposure. Qu and colleagues also evaluated whether the number and type of blood cells decreased in the exposed subjects because such decreases may be early indicators of a response to occupational benzene exposure. Some biological samples were analyzed in China and some in the United States.