Nonlinear Low Dose Hematotoxicity Of Benzene; A Pooled Analyses Of Two Studies Among Chinese Exposed Workers

Roel VERMEULEN, Utrecht University, Netherlands

1 Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
2 Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, MD 20892

Impairment of the hematopoietic system is one of the primary adverse health effects after exposure to benzene. We previously have shown that benzene at lower levels of exposure (<1 ppm) effect the blood forming system. Here we extend these analyses by detailed modeling of the exposure response association of benzene and its major metabolites (i.e. catechol, muconic acid, phenol, and hydroquinone) on peripheral white blood cell counts (WBCs) and its major cell-subtypes (i.e. granulocytes, lymphocytes, and monocytes) using two previously published cross-sectional studies among occupationally exposed Chinese workers.  Clear non-linear exposure response associations were observed between air benzene concentrations and WBCs and its cell-subtypes with a larger than proportional decrease in cell counts at lower than at higher levels of benzene exposure (exposure range 0.1 – 100ppm). This association was largely similar in shape (supralinear) when the analyses were repeated with the measured benzene metabolites and as such enzymatic saturation processes do not seem to explain the observed non-linearity. An analyses on the risk of having a WBC count below 4000 cells/ul showed that this association was essentialy linear. Together, these results suggest that the non-linearity in the observed hematological effects may be explained by increased cell proliferation, while the risk of having a WBC count below 4000 cells/ul is a result of both hematotoxicity and failure to compensate for this effect.