Tardif R, Goyal R, Brodeur J, Gérin M
Département de médecine, Faculté de médecine, Université de Montréal, Québec, Canada.
Fundam Appl Toxicol. 1987 Oct;9(3):448-53. doi: 10.1016/0272-0590(87)90027-3.
Some aspects of the qualitative and quantitative urinary disposition of some metabolites of ethylene oxide in three rodent species, mouse, rat, and rabbit, were examined by determining urinary N-acetyl-S-(2-hydroxyethyl)-L-cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and ethylene glycol after ethylene oxide exposure by iv and inhalation routes. The animals were given ethylene oxide at 20 and 60 mg/kg, and urine samples were collected at 6 and 24 hr. Important differences were observed between the three species in the urinary metabolic disposition of ethylene oxide. Mice excreted significant quantities of N-acetyl-S-(2-hydroxyethyl)-L-cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and ethylene glycol (8.3, 5.8, 1.9, and 3.3% of the lower dose, respectively, in 24 hr), whereas in rats only N-acetyl-S-(2-hydroxyethyl)-L-cysteine (31%) and ethylene glycol (6%) were apparent. In contrast, the rabbits were found to excrete only ethylene glycol (2%). This study further reveals species-related differences in the urinary excretion of N-acetyl-S-(2-hydroxyethyl)-L-cysteine and ethylene glycol during the two collection periods. The observed differences between the three species in the metabolic disposition of ethylene oxide were found to be qualitatively independent of the route of exposure, i.e., inhalation at 200 ppm or iv. These results suggest that care should be exercised when using an animal species as a model for human disposition of ethylene oxide.
通过静脉注射和吸入途径给予环氧乙烷后，测定小鼠、大鼠和兔子三种啮齿动物尿液中N-乙酰-S-(2-羟乙基)-L-半胱氨酸、S-(2-羟乙基)-L-半胱氨酸、S-羧甲基-L-半胱氨酸和乙二醇，研究了环氧乙烷某些代谢物在尿液中的定性和定量分布的一些方面。给动物分别注射20和60mg/kg的环氧乙烷，并在6小时和24小时收集尿液样本。在环氧乙烷的尿液代谢分布方面，观察到这三种动物之间存在重要差异。小鼠排泄出大量的N-乙酰-S-(2-羟乙基)-L-半胱氨酸、S-(2-羟乙基)-L-半胱氨酸、S-羧甲基-L-半胱氨酸和乙二醇（24小时内分别占较低剂量的8.3%、5.8%、1.9%和3.3%），而在大鼠中，仅N-乙酰-S-(2-羟乙基)-L-半胱氨酸（31%）和乙二醇（6%）较为明显。相比之下，发现兔子仅排泄乙二醇（2%）。这项研究进一步揭示了在两个收集时间段内，N-乙酰-S-(2-羟乙基)-L-半胱氨酸和乙二醇在尿液排泄方面存在物种相关差异。发现这三种动物在环氧乙烷代谢分布上的差异在性质上与暴露途径无关，即200ppm吸入或静脉注射。这些结果表明，在将动物物种用作人类环氧乙烷分布模型时应谨慎。
