Benzene, genotoxic activity

The objective of chemical safety testing is to prevent the introduction into the environment of chemicals that represent a significant health hazard to humans or to the immediate environment on which maintenance of the human species depends. For chemicals that must remain in the environment for one reason or another, safety testing can be used to establish a safe or tolerable exposure level. The potential benefit of test results from evaluations for genotoxicity applied to human health considerations can be substantiated by the early indications of genotoxic activity for vinyl chloride, tris-(2,3-dibromo-propyl) phosphate (TRIS), benzene, hycanthone, and the Japanese food additive 2-(2-furyl)-3-(5-nitrofuryl)acrylamide(AF-2). In some of these cases, mutagenic data were available before the chemicals were identified as animal carcinogens. 

Ciranni R, Barale R, Marrazzini A, etal. 1988. Benzene and the genotoxicity of its metabolites. I. Transplacental activity in mouse fetuses and in their dams. Mutat Res 208 61-67. 

Data also exist that suggest that benzene itself is genotoxic. Two studies reported that benzene produced DNA breaks in Chinese hamster ovary cells independent of metabolic activators (Douglas et al. 1985 Lakhanisky and Hendrickx 1985). In a study by Aubrecht et al. (1995), benzene was shown to induce intrachromosomal recombination in human lymphoblastoid cell culture. Therefore, benzene appears to have some genotoxic capabilities of its own, but its metabolites seem to be the primary genotoxins in systems in which normal metabolism is occurring. Refer to Table 2-6 for the results of these and other in vitro studies. 

Glatt H, Padykula R, Berchtold GA, et al. 1989. Multiple activation pathways of benzene leading to products with varying genotoxic characteristics. Environ Health Perspect 82 81-89. 

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