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Benzene Exposure Assessed by Metabolite Excretion in Estonian Oil Shale Mineworkers: Influence of Glutathione S-Transferase Polymorphisms

¹ Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; ² Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton, United Kingdom; ³ Department of Environmental and Occupational Medicine, University of Aarhus, Aarhus, Denmark; and ⁴ Institute of Experimental and Clinical Medicine, Tallinn, Estonia

Requests for reprints: Lisbeth E. Knudsen, Institute of Public Health, Department of Pharmacology, Panum Institute, Room 18-5-42, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Phone: 45-35327653; Fax: 45-35327610. E-mail: l.knudsen{at}pubhealth.ku.dk

Measurement of urinary excretion of the benzene metabolites S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) has been proposed for assessing benzene exposure, in workplaces with relatively high benzene concentrations. Excretion of S-PMA and t,t-MA in underground workers at an oil shale mine were compared with the excretion in workers engaged in various production assignments aboveground. In addition, possible modifying effects of genetic polymorphisms in glutathione S-transferases T1 (GSTT1), M1 (GSTM1), and P1 (GSTP1) on the excretion of S-PMA and t,t-MA were investigated. Fifty underground workers and 50 surface workers participated. Blood samples and three urine samples were collected from each worker: (a) a preshift sample collected the morning after a weekend, (b) a postshift sample 1 collected after the first shift, and (c) a postshift sample 2 collected after the last shift of the week. Personal benzene exposure was 114 ± 35 µg/m³ in surface workers (n = 15) and 190 ± 50 µg/m³ in underground workers (n = 15) in measurements made prior to the study. We found t,t-MA excretion to be significantly higher in underground workers after the end of shifts 1 and 2 compared with the corresponding surface workers. The same picture, although not significant, was seen for S-PMA excretion. Excretion of S-PMA and t,t-MA was found to increase significantly during the working week in underground workers but not in those employed on the surface. Both t,t-MA and S-PMA excretion were significantly higher in smokers compared with nonsmokers. Subjects carrying the GSTT1 wild-type excreted higher concentrations of S-PMA than subjects carrying the null genotype, suggesting that it is a key enzyme in the glutathione conjugation that leads to S-PMA. The results support the use of benzene metabolites as biomarkers for assessment of exposure at modest levels and warrant for further investigations of health risks of occupational benzene exposure in shale oil mines.

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