Hanley T R, Schumann A M, Langvardt P W, Rusek T F, Watanabe P G
Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674.
Toxicol Appl Pharmacol. 1989 Aug;100(1):24-31. doi: 10.1016/0041-008x(89)90088-4.
Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as 14CO2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of 13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [14C]EG (141 mg/kg), approximately 37% of the dose was expired as 14CO2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified.
碳酸亚乙酯（EC）的毒性特征与乙二醇（EG）相似。为了确定EC的毒性是否可以基于其代谢为EG来解释，给雄性Fischer 344大鼠经口灌胃给予200 mg/kg均匀标记的[14C]EC水溶液，然后追踪放射性标记物的处置情况72小时。EC迅速代谢，分别约有57%和27%的给药剂量以14CO2形式经呼气排出以及经尿液排出；其余部分存在于 carcass中。使用液相色谱法分离尿液代谢产物显示出一个单一的放射性峰。借助EC剂量的13C富集，通过气相色谱-质谱法明确鉴定该代谢产物为乙二醇。给大鼠经口灌胃给予200 mg/kg EC后，测定大鼠全血中EC和EG的水平，结果显示EG的血药浓度比这些动物中EC的浓度高约100倍，EG在血液中的半衰期为2小时，表明EC迅速转化为EG。在另一组给予等摩尔剂量[14C]EG（141 mg/kg）的动物中，约37%的剂量以14CO2形式呼出，42%以母体化合物形式经尿液排出。基于乙二醇部分计算，EC的处置情况与EG相同。鉴于EC迅速且广泛地生物转化为EG，以及与EG相比EC现有的（尽管有限）毒性数据库具有相似性，利用广泛的EG全身毒性数据库来评估EC的安全性似乎是合理的。
