A brief survey of butadiene health effects: a role for metabolic differences.

Abstract

1,3-Butadiene is a major monomer in the rubber and plastics industry and is one of the highest-production industrial chemicals in the United States. Although not highly acutely toxic to rodents, inhalation of concentrations as low as 6.25 ppm causes tumors in mice. Butadiene is oncogenic in rats, but much higher exposure concentrations are required than in mice. Chronic toxicity targets the gonads and hematopoetic system. Butadiene is also a potent mutagen and clastogen. Differences in the absorption, distribution, and elimination of butadiene appear to be relatively minor between rats and mice, although mice do retain more butadiene and its metabolites after exposure to the same concentration and have a higher rate of metabolic elimination. Recent studies have demonstrated that major species differences appear to occur in the rate of detoxication of the primary metabolite, 3-epoxybutene (butadiene monoepoxide [BDMO]). Mice have the greatest rate of production of BDMO as compared to other species, but the rate of removal of BDMO appears to be less than in other species. Mice have low levels of epoxide hydrolase; rats have intermediate levels; monkeys and humans appear to have high levels of this detoxifying enzyme. Thus, while only low levels of butadiene exposure may result in an accumulation of BDMO in the mouse, much higher levels would be required to result in an elevation of circulating BDMO in other species. The level of this reactive metabolite may be correlated with the species differences in butadiene sensitivity.

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“…I became the project officer for a large disposition contract with the Lovelace Inhalation Toxicology Research Institute. Working collaboratively, I helped design and interpret a series of inhalation studies on the pharmacokinetics of benzene (33,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53), butadiene (54)(55)(56)(57)(58), and other major industrial toxicants; PBPK modeling was utilized in study design and interpretation. It was exciting and important work that allowed me to claim I knew something about inhalation toxicology, which led to a major career move.…”

In Vivo Roles of Conjugation with Glutathione and O6-Alkylguanine DNA-Alkyltransferase in the Mutagenicity of the Bis-Electrophiles 1,2-Dibromoethane and 1,2,3,4-Diepoxybutane in Mice

“…1,3-Butadiene is used in the synthetic rubber industry, and its annual use in the United States is ∼2 × 10 9 kg. , It is carcinogenic in rodents (much more in mice than rats) and has been classified as “carcinogenic to humans” by the IARC . There is also concern about exposure to humans from other sources, e.g., cigarette smoke. , …”