Lymphoma benzene-induced

The potential for a nonhnear extrapolation from human data should also be considered. Some risk assessors have argued that benzene-induced leukemia and lymphoma is a threshold phenomenon, based on mechanistic considerations, and that the human data demonstrate such a threshold (Cox and Ricci 1992 Cox 1996 Yokley et al. 2006). However, regulatory risk assessors have not yet accepted these arguments for benzene (Bailer and Hoel 1989 ERA 1998 OEHHA 2001). Considerations include the multiple genotoxic metabolites of benzene, a nonlinear production of protein and DNA adducts in humans (saturated at higher benzene doses), and the difficulty of establishing dose-response relationships at lower doses with the available animal and human data (Bailer and Hoel 1989 Henderson et al. 1992 Turteltaub and Mani 2003 Rappaport et al. 2005 Lin et al. 2007). 

Ethyl benzene is not mutagenic in most test systems, but it has caused a mutagenic effect in mouse lymphoma cells and has induced a marginal yet significant increase in sister chromatid exchanges in human lymphocytes at toxic doses." ... 

Although precise occupational exposures were not known, most studies indicated that workers had been exposed to concentrations up to 250-300 ppm during at least part of a working day thus, 300 ppm was chosen. The C57BL/6 and CBA/Ca mouse strains were chosen for these studies because of their susceptibilities to ionizing radiation-induced thymic lymphoma. The strains are also recognized for their low spontaneous rates of AML, the disease most frequently associated with benzene exposure in humans. 

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