CHAPTER 32: Butadiene and Its Effects on Micronucleus Frequency

1,3-Butadiene (BD) is a volatile compound widely used in the production of synthetic rubbers. BD has been classified as “carcinogenic to humans” by the International Agency for Research on Cancer (IARC) because an association between occupational exposure to BD and increased risk of leukemia was shown. Interspecies difference in susceptibility to BD carcinogenicity has been observed, with mice being more sensitive than rats. The key steps of BD carcinogenicity involve the metabolic activation of BD to different epoxides known to bind to DNA, leading to mutations. BD was shown to be genotoxic in different in vitro systems only in the presence of metabolic activation. Ten in vivo MN-assays carried out in mice showed consistently positive results in bone marrow. Two studies in rats reported negative results. Four small sized studies using the MN assay in peripheral lymphocytes of subjects occupationally exposed to 1–3 ppm of BD did not show any increase in MN frequency. Three studies recently carried out in China showed increased MN frequencies associated with the intensity of the exposure, with a frequency ratio of 2.29 when the mean cumulative dose was 266 ppm year⁻¹. These results are consistent with the exposure–response curve for leukemia mortality, showing no increase for cumulative exposure of less than or equal to 200 BD ppm-years.