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Exposure to low levels of benzene, interindividual biologicalvariability and cancer risk: a multicentre European study


Benzene is a ubiquitous pollutant, to which people are exposed from both occupational and environmental sources These include a number of industrial processes, exposure to gasoline, cigarette smoking, automobile exhaust, and others Benzene is a human carcinogen which has been specifically associated with leukemia in several populations with high occupational exposures. There are many uncertainties related to benzene exposure, health effects and mechanisms. This especially applies to situations of low exposure levels (<10 ppm) which are quite common in modern Europe, and for which very little of information is available.
This project involves the study of a number of cohorts of European workers exposed to low levels of benzene The cohorts include petrochemical workers from Bulgaria, Italy and Great Britain, filling station attendants and traffic wardens from Genoa and Milan in Italy, and bus drivers from Genoa. The range of benzene exposures in these cohorts is from 0.01 to 10 ppm, and the total number of workers is in excess of 80,000. Information is available for these cohorts on occupational history, smoking history, occupational hygiene data including ambient air monitoring, and in some cases blood benzene levels.
A cross-sectional study will be conducted on samples of actively employed workers from each of the cohorts to be studied in the project, with controls chosen from suitable non-exposed populations. Biomarkers will be employed along with benzene air measurements to precisely characterize individual exposure levels. The biomarkers to be used include trans,trans-muconic acid as a marker of internal dose; benzene oxide-hemoglobin-S-phenylcysteine adducts as a marker of biologically effective dose; and differential white blood cell count, and single strand breaks in leukocyte DNA as markers of early biological effect. In addition we will determine the genotype of each individual, with respect to polymorphisms of the CYP2El and NQO1 genes, to address the hypothesis that individual differences in sensitivity to the biological effects of benzene exposure may be related to genetic differences in the function of these benzene metabolizing genes.
A historical mortality study of workers from part of the occupationally exposed cohorts will be done, and results compared with those from other studies. The focus of this work will be on the Italian and Bulgarian cohorts, for which either little (Italian) or no (Bulgarian) previous data have been generated. This part of the project will include workers actively employed between 1970 and 1980, with a follow-up period of 30 years. Standardized Mortality Ratio analysis will be done to adjust for inter-country specific differences in background mortality.
This project, using a multicenter approach, will further clarify the role of low level occupational benzene exposures in Europe, and will integrate data on several biological markers of exposure, effect and susceptibility with health outcomes in the same study populations. Results from the project should contribute significantly to the high priority research needs on benzene as articulated by a WHO panel in 1993. The data should also have profound importance in building a scientific basis for regulatory decisions aimed at prevention of occupationally and environmentally induced disease in Europe.
Key words: Benzene, Cancer, Occupation, Biomarkers, Epidemiology, Genetic Susceptibility


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Largo Rosanna Benzi 10
16132 GENOVA

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