Sister chromatid exchanges induced in rabbit lymphocytes by ethylene oxide after inhalation exposure

Ethylene oxide, which is the simplest epoxide and an extremely important commercial compound, has been used by many investigators as a model compound to study mutagenicity by alkylation of DNA. Knowledge of in vivo dose-effect relations under experimental conditions may provide further insight into the dynamics of the sister chromatid exchange (SCE) response. It may also provide information on temporal aspects of sampling design for human worker populations. Groups of four male New Zealand white rabbits were exposed in inhalation chambers to 0, 10, 50, and 250 parts per million (ppm) ethylene oxide for 6 hr a day, 5 days a week, for 12 weeks. Peripheral blood samples were taken before the start of exposure, at intervals during exposure, and up to 15 weeks after the end of exposure to measure SCE rates in peripheral lymphocytes as well as standard hematological endpoints. Additionally, the level of reduced glutathione (GSH) in liver and blood was measured in a set of concurrently exposed animals at the end of the 12-week exposure. Results show that exposure to 10 ppm does not cause a detectable increase in SCE rates. However, exposure to 50 and 250 ppm does cause an increase in SCEs that decreases after exposure ends, but still remains above baseline levels 15 weeks after exposure. Hematological and GSH measurements did not differ between control and exposed groups. These results indicate that inhalation exposure to the mutagenic alkylating agent ethylene oxide results in a dose-related SCE effect, and that SCE is a more sensitive indicator of exposure than either standard hematological end points or GSH levels.