ARTICLE NO. FA972383 Rat Olfactory Mucosa Displays a High Activity in Metabolizing Methyl te/t-butyl Ether and Other Gasoline Ethers

Methyl terf-butyl ether (MTBE) is a widely used gasoline oxy-genate. Two other ethers, ethyl fert-butyl ether (ETBE) and tert-amyl methyl ether (TAME), are also used in reformulated gasoline. Inhalation is a major route for human exposure to MTBE and other gasoline ethers. The possible adverse effects of MTBE in humans are a public concern and some of the reported symptoms attributed to MTBE exposure appear to be related to olfactory sensation. In the present study, we have demonstrated that the olfactory mucosa of the male Sprague-Dawley rat possesses the highest microsomal activities, among the tissues examined, in me-tabolizing MTBE, ETBE, and TAME. The metabolic activity of the olfactory mucosa was 46-fold higher than that of the liver in metabolizing MTBE, and 37- and 25-fold higher, respectively, in metabolizing ETBE and TAME. No detectable activities were found in the microsomes prepared from the lungs, kidneys, and olfactory bulbs of the brain. The observations that the metabolic activity was localized exclusively in the microsomal fraction, de-pended on the presence of NADPH, and was inhibitable by carbon monoxide are consistent with our recent report on MTBE metabo-lism in human and mouse livers (Hong et al., 1997) and further confirm that cytochrome P450 enzymes play a critical role in th