Hematotoxicity in workers exposed to low levels of benzene

Abstract

Benzene is known to have toxic effects on the blood and bone marrow, but its impact at levels below the U.S. occupational standard of 1 part per million (ppm) remains uncertain. In a study of 250 workers exposed to benzene, white blood cell and platelet counts were significantly lower than in 140 controls, even for exposure below 1 ppm in air. Progenitor cell colony formation significantly declined with increasing benzene exposure and was more sensitive to the effects of benzene than was the number of mature blood cells. Two genetic variants in key metabolizing enzymes, myeloperoxidase and NAD(P)H:quinone oxidoreductase, influenced susceptibility to benzene hematotoxicity. Thus, hematotoxicity from exposure to benzene occurred at air levels of 1 ppm or less and may be particularly evident among genetically susceptible subpopulations.

Fig. 1

Effect of benzene exposure on (A) white blood cell (WBC) and granulocyte counts; (B) colonies from the colony-forming unit–granulocyte-macrophage (CFU-GM) and burst-forming unit–erythroid (BFU-E); and (C) colonies from the colony-forming unit–granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM). Erythropoietin (EPO) was added to half of the cultures (). Trends with benzene were tested by linear regression (WBC, granulocytes), negative binomial regression (CFU-GM, BFU-E), and unconditional logistic regression [CFU-GEMM, categorizing subjects into 0 or more than 0 colonies (92%, 74%, and 40% of subjects had >0 colonies among controls, <10 ppm, and ≥10 ppm, respectively)]. Models were adjusted for age and sex, and additionally for smoking, alcohol, recent infections, and body mass index (BMI) if significant (). Strong, inverse trends between benzene and all cell types were present (P_trend shown). There was a greater proportional decrease in colonies in workers exposed to ≥10 ppm versus controls for CFU-GM, BFU-E, and CFU-GEMM compared to the decline in WBCs (P < 0.011, 0.048, and 0.0078, respectively) and for CFU-GM and -GEMM compared to the decline in granulocytes (P = 0.026 and 0.0094, respectively) ().