The ex vivo L-CBMN assay detects significant human exposure to butadiene

Abstract

1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in rodents revealed widely different BD carcinogenic/mutagenic potency in rat and mice, associated to differences in BD metabolism. The available biomonitoring studies in workers occupationally exposed to BD, considering different genetic endpoints, do not allow to reach a conclusion on the BD carcinogenic/mutagenic risk in humans. The present systematic review retrieves and analyzes the published studies on the application of the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) of BD exposed subjects. Ten articles were retrieved related to seven studies on BD exposure and one study on exposure to a mixture of compounds in a styrene-butadiene tire manufacturing plant. Four studies carried out in Europe related to heterogeneous groups of workers exposed in BD monomer or polymer manufacturing and processing industries, reporting mean individual exposure levels below 3ppm, failed to find any increase of MN frequency. Three studies, including mixed groups of workers involved in different stages of the production and manufacturing of BD in China, show increased MN frequencies associated with the intensity of the exposure, with a relevant positive response (FR=2.29) when the mean cumulative dose was estimated as 266ppm/year. These results are consistent with the data on the exposure-response curve for total leukemia mortality showing no increase for cumulative exposure less than or equal to 200 BD ppm-years. The L-CBMN assay, measuring both chromosome breakage and chromosome loss, events involved in induction of leukemia, seems to be a promising biomarker for cancer risk induced by BD.

Keywords: 1,3-Butadiene; Biomonitoring; Carcinogenicity; Genotoxicity; Lymphocyte cytokinesis-block micronucleus; Systematic review.