Clastogenic effects of 1,3-butadiene and its metabolites 1,2-epoxybutene and 1,2,3,4-diepoxybutane in splenocytes and germ cells of rats and mice in vivo.

Abstract

Clastogenicity of 1,3-butadiene (BD), 1,2-epoxybutene (EB), and 1,2,3,4-diepoxybutane (DEB) was studied in splenocytes and germ cells of rats and mice by means of micronucleus assays (cytokinesis-block method for splenocytes, suspension method for germ cells). Inhalation exposure of mice to 200, 500, or 1,300 ppm BD (6 h/d; 5 days) induced significant chromosome damage in spermatocytes at the preleptotene stage. EB and DEB induced significant amounts of clastogenic damage in splenocytes and spermatocytes of rats and mice. The lowest tested effective doses for mice and rats were, respectively, 40 and 80 mg/kg for EB, and 15 and 30 mg/kg for DEB. In splenocytes, 80 mg EB/kg induced 3.6 times more MN in mice than in rats, whereas 30 mg DEB/kg induced the same amount of damage in both species. Damage in germ cells of mice was induced in early spermatocytes treated with 40 and 80 mg EB/kg, and in late spermatocytes exposed to 30 mg DEB/kg. In rats, 40 mg EB/kg induced damage in early spermatocytes, whereas 80 mg EB/kg induced chromosomal damage in early and late spermatocytes. In rats treated with DEB, clastogenic damage was induced in spermatocytes at preleptotene, zygotene, diplotene, and diakinesis stages. When the clastogenic potential of EB and DEB in splenocytes and germ cells of mice and rats was compared, DEB always showed a stronger effect than EB. Body weight, testis weight, ratio of testis weight to body weight, and ratio of Golgi to Golgi + cap phase spermatids were used as parameters for toxicity. Exposures to 500 and 1,300 ppm BD were somewhat toxic to mice. Doses of 80 mg EB/kg and 30 mg DEB/kg exhibited toxic effects in mice and rats.