Isoprene: background and issues.

Isoprene monomer is derived from petroleum cracking and is used in the manufacturing of polyisoprene, butyl rubber and a variety of copolymers. It is also the monomeric unit of naturally occurring terpenes (e.g. lycopenes, the pigmentation in tomatoes). Isoprene occurs in tobacco smoke and it is released by a wide range of plants and mammals (including man). Portion of the isoprene present in the atmosphere is therefore from natural origin. Isoprene is chemically closely related to butadiene. Both substances are being used in similar industrial processes and because of the structural analogy, it is often speculated that the toxicological properties of isoprene must resemble those of butadiene. In fact, the acute toxicity of isoprene is very similar and also the biotransformation to mono- and diepoxides is qualitatively alike. There is however a difference; isoprene is asymmetric and therefore more metabolic enantiomers are possible. Pharmacokinetic studies have demonstrated species differences (as with butadiene) in the maximum metabolic elimination rate: in mice this was determined to be at least three times higher than in rats which implies a species sensitivity in isoprene metabolism in the mouse. Both isoprene and its major metabolites were tested for mutagenic activity in Salmonella strains. Only the diepoxide was found to be positive in TA100. In in vivo cytogenetic tests in mice, no chromosomal aberrations were observed but an increase in SCEs and micronuclei was evident. As is the case with butadiene there are clear indications from long-term rat/mice inhalational studies with isoprene of a species difference in tumour response. Based on cytogenetic findings and tumorigenicity data it is clear that isoprene is less potent than butadiene. Such observations are important and useful to reduce uncertainties in risk-characterisation procedures (e.g. occupational exposure standard setting; EU existing chemicals regulations).