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88856 
Journal Article 
Levels of epoxides in blood during inhalation of alkenes and alkene oxides 
Maples, KR; Dahl, AR 
1993 
Yes 
Inhalation Toxicology
ISSN: 0895-8378
EISSN: 1091-7691 
5 
1 
43-54 
WOS:A1993KQ82800003 
We previously reported that propylene oxide levels in the blood of rats exposed to propylene spiked 5–10 min into the exposure and that hepatic and nasal cytochrome P-450 concentrations decreased relative to control values after the occurrence of the propylene oxide spike. These results can be explained by the inactivation of enzymes both efficient at propylene epoxidation and susceptible to inactivation by terminal alkene metabolites. To further examine this phenomenon, we exposed rats to ethylene, a known cytochrome P-450 inactivator; to cyclohexene, an alkene that does not inactivate cytochrome P-450; and to the epoxides of ethylene, cyclohexene, and propylene. During a 600-ppm ethylene exposure, blood ethylene oxide levels rapidly increased for the first 5–10 min and then rapidly declined to remain relatively constant for the duration of a 60-min exposure. Hepatic cytochrome P-450 decreased throughout the ethylene exposure. During exposure to 5 ppm ethylene oxide, blood epoxide concentrations gradually increased and reached a plateau after 15 min of exposure. Hepatic cytochrome P-450 was not affected. Exposure to 600 ppm cyclohexene resulted in no detectable epoxide and no change in hepatic cytochrome P-450. Exposure to 30 ppm cyclohexene oxide produced no changes in hepatic cytochrome P-450 levels, although blood epoxide levels increased during the first 25 min of exposure and then leveled off. During exposure to 14 ppm propylene oxide, blood epoxide levels increased for the first 10 min and then leveled off. No changes in hepatic cytochrome P-450 were found. The results are consistent with our earlier observations that exposures to alkenes that inactivate cytochrome P-450 result in an early spike of blood levels of the epoxide. This phenomenon could have important toxicological implications.