Metabolism and toxicity of 2-methylpropene (isobutene)--a review.
2-Methylpropene (MP) or isobutene is a gaseous chemical used on a large scale in the synthetic rubber industry. The present review covers the rather scarce literature on MP with respect to its metabolic fate and toxicity in laboratory animals and humans. It has been shown both in vivo and in vitro that MP is metabolized to the primary metabolite 2-methyl-1,2-epoxypropane (MEP) by rodent and human liver tissue. The formation of this reactive epoxide intermediate is catalyzed by CYP2E1, while epoxide hydrolase and glutathione S-transferase appear to be involved in its inactivation. In rats, the capacity to absorb and metabolize MP is saturable. MP is oxidized to compounds that are mainly excreted in urine. Data indicate that rodents can tolerate low levels of MP without apparent toxicity. The primary metabolite MEP, however, is able to produce genetic damage in both prokaryotic and eukaryotic cells in vitro. MP is thus not toxic per se but elicits metabolic activation to become potentially harmful. Consequently, the balance between formation and detoxification of MEP plays a key role in determining the potential toxicity of the parent compound. Obviously, further research, including repeated exposure toxicity studies, is required before an estimation of the risk for man can be made.