MOLECULAR AND GENETIC TOXICOLOGY OF 1,3-BUTADIENE

During the last 9 years, there have been many studies published concerning the mutagenic potential of butadiene in mammalian systems, including alterations at the molecular level. Butadiene has tested positive in several mouse in vivo and in vitro assays, but has generally tested negative in rat studies. Most of these studies are cytogenetic and include positive data in mice for chromosomal aberrations, micronucleus formation, and sister chromatid exchanges. Butadiene also induces mutations in lung, spleen, and bone marrow of transgenic mice. The positive bone marrow cytogenetic and transgenic data may be significant in view of the increased lymphohematopoietic malignancies observed in mice and probably in humans. In addition, butadiene causes mutations in the K-ras protooncogene and in the p53 tumor suppressor gene in mouse studies. Mutations in these genes are associated with oncogenesis in humans as well as in rodents. Also, positive mutagenicity data have been obtained in a pilot study of workers exposed to butadiene. Positive dominant lethal studies in rodents suggest that exposure to butadiene can result in germ cell mutation and heritable risk. These mutagenicity and molecular data suggest that butadiene is both a somatic and germ cell mutagen in mammals, possibly including humans.