Taalman R D
Shell International B.V., The Hague, The Netherlands.
Toxicology. 1996 Oct 28;113(1-3):242-6. doi: 10.1016/0300-483x(96)03452-x.
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).
异戊二烯单体来源于石油裂解，用于制造聚异戊二烯、丁基橡胶和各种共聚物。它也是天然存在的萜类化合物（如番茄红素，番茄中的色素）的单体单元。异戊二烯存在于烟草烟雾中，并且由多种植物和哺乳动物（包括人类）释放。因此，大气中存在的部分异戊二烯来自天然来源。异戊二烯在化学上与丁二烯密切相关。这两种物质都用于类似的工业过程，并且由于结构相似，人们常常推测异戊二烯的毒理学特性一定与丁二烯相似。事实上，异戊二烯的急性毒性非常相似，并且其向单环氧化物和二环氧化物的生物转化在性质上也是相似的。然而存在一个差异；异戊二烯是不对称的，因此可能存在更多的代谢对映体。药代动力学研究已经证明（与丁二烯一样）在最大代谢消除率方面存在种属差异：在小鼠中，这一速率至少比大鼠高3倍，这意味着小鼠对异戊二烯代谢具有种属敏感性。异戊二烯及其主要代谢产物都在沙门氏菌菌株中进行了致突变活性测试。仅二环氧化物在TA100中呈阳性。在小鼠体内细胞遗传学试验中，未观察到染色体畸变，但姐妹染色单体交换和微核增加明显。与丁二烯的情况一样，长期对大鼠/小鼠进行异戊二烯吸入研究的明确迹象表明在肿瘤反应方面存在种属差异。基于细胞遗传学研究结果和致癌性数据，很明显异戊二烯的毒性比丁二烯小。这些观察结果对于减少风险表征程序（例如职业接触标准设定；欧盟现有化学品法规）中的不确定性非常重要且有用。
