Determination of leukemogenic benzene exposure concentrations: refined analyses of the Pliofilm cohort.

Biologic data on benzene metabolite doses, cytotoxicity, and genotoxicity often show that these effects do not vary directly with cumulative benzene exposure (i.e., concentration times time, or c x t). To examine the effect of an alternate exposure metric, we analyzed cell-type specific leukemia mortality in Pliofilm workers. The work history of each Pliofilm worker was used to define each worker's maximally exposed job/department combination over time and the associated long-term average concentration associated with the maximally exposed job (LTA-MEJ). Using this measure, in conjunction with four job exposure estimates, we calculated SMRs for groups of workers with increasing LTA-MEJs. The analyses suggest that a critical concentration of benzene exposure must be reached in order for the risk of leukemia or, more specifically, AMML to be expressed. The minimum concentration is between 20 and 60 ppm depending on the exposure estimate and endpoint (all leukemias or AMMLs only). We believe these analyses are a useful adjunct to previous analyses of the Pliofilm data. They suggests that (a) AMML risk is shown only above a critical concentration of benzene exposure, measured as a long-term average and experienced for years, (b) the critical concentration is between 50 and 60 ppm when using a median exposure estimate derived from three previous exposure assessments, and is between 20 and 25 ppm using the lowest exposure estimates, and (c) risks for total leukemia are driven by risks for AMML, suggesting that AMML is the cell type related to benzene exposure.