Benzene and Leukemia

Abstract

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.

Review and update of leukemia risk potentially associated with occupational exposure to benzene.

“…The opinions of these hematology experts suggest that the Crump and Allen original exposure estimates, derived from industrial hygiene data, are preferable to the Crump and Allen alternative estimates (37). Thus (20,21). In this analysis, each of the 9 leukemia cases was matched to 10 controls by year of birth and year first employed.…”

“…We will describe the four studies that have been most frequently used for this purpose (9,20,21) are reports representing continued follow-up of the leukemia mortality experience of a group of Goodyear workers who had been exposed to benzene in the manufacture of rubber hydrochloride (also known as Pliofilm) at three facilities at two locations in Ohio. We shall limit our discussion to the methodology and results obtained in the latter two Rinsky reports, as these have been the primary basis for the more recent risk assessments.…”

Hematopoietic Effects of Benzene Inhalation Assessed by Long-Term Bone Marrow Culture

“…Excessive benzene exposure in humans and other mammals often results in disorders such as leukemia and aplastic anemia (3,5). Disturbed or impaired stroma may contribute to abnormal hematopoiesis and thus to the pathogenesis of these disorders (32,33).…”

“…Chronic exposure of animals to benzene is known to lead to progressive degeneration of the bone marrow and the drug metabolic system, leukopenia, aplastic anemia, and eventual leukemia (1)(2)(3)(4). The clinical evidence indicating benzene as a primary inducer of diseases such as aplastic anemia and leukemia is well documented (5). Benzene can produce such toxic metabolites as phenol, catechol, and hydroquinone; apparently these agents can accumulate in the bone marrow (6)(7)(8).…”

A note on myeloperoxidation index and its correlation to the biomarker, urine trans, trans-muconic acid level, in the subjects occupationally exposed to benzene

“…1 At present, benzene is a wellknown toxic agent acting as a primary inducer of leukemia. 2 Although the mechanisms underlying benzene-induced toxicity and leukemogenicity are not yet fully understood, they are likely to be complicated by various pathways, including those of metabolism, growth factor regulation, oxidative stress, DNA damage, cell cycle regulation, and programmed cell death. 3 The potential metabolic mechanisms underlying the hemopoietic toxicity of benzene include bioactivation of phenolic metabolites of benzene by myeloperoxidases in the bone marrow and ring opening reactions to generate muconate derivatives.…”