Benzene and Leukemia

To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million–years (ppm-years), to 40 to 199, 200 to 399, and 400 or more, respectively. A cumulative benzene exposure of 400 ppm-years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure–response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene-induced leukemia would increase exponentially with any reduction in the permissible exposure limit. (N Engl J Med 1987;316:1044–50.) AN etiologic association between benzene and leuL kemia was suggested by a series of case reports beginning more than 50 years ago. 1 2 3 4 5 6 Those clinical observations were corroborated subsequently by epidemiologic studies 5 , 7 8 9 10 11 and, more recently, by carcinogenesis bioassays. 12 13 14 15 Benzene is now generallyconsidered by national and international scientific bodies to be a human carcinogen. 16 17 18 To reduce the risk of leukemia in industrial workers exposed to airborne benzene, the U.S. Occupational Safety and Health Administration (OSHA) promulgated in 1978 an occupational-exposure standard that reduced the permissible workplace concentrations of benzene 10-fold, 19 from the previously acceptable eight-hour time-weighted average of 10 ppm in air . . .