Species differences in the urinary disposition of some metabolites of ethylene oxide

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.