NEUROTOXICOLOGICAL EVALUATION OF METHYL TERTIARY-BUTYL ETHER IN RATS

Methyl tertiary-butyl ether (MTBE) is an oxygenate that is added to ga soline to boost octane and enhance combustion, thereby reducing carbon monoxide and hydrocarbon tailpipe emissions. The acute and subchronic neurotoxicity of MTBE were evaluated in rats using a functional obser vation battery (FOB), measures of motor activity (MA) and a neuropatho logical evaluation. In the acute study, rats were exposed once to 0, 8 00, 4000 or 8000 ppm MTBE by inhalation for 6 h and then evaluated thr ee times over a 24-h period. In the FOB evaluations, treatment-related effects were seen at the 1-h session immediately following exposure a nd were indicative of transient central nervous system (CNS) depressio n. Effects were most apparent in the high-dose group (8000 ppm) but we re also evident to a lesser extent in the mid-dose (4000 ppm) group. L abored respiration, ataxia, duck-walk gait and decreases in muscle ton e, hind-limb grip strength and treadmill performance were the most fre quently noted findings. No significant effects were observed in the FO B when testing was conducted at 6 h and 24 h post-exposure. The patter n of motor activity measured in the different dose groups following ex posure was also in keeping with a reversible CNS-depressant effect of MTBE. In the subchronic study, rats were exposed to 0, 800, 4000 or 80 00 ppm MTBE for 6; h a day, 5 days per week, for 13 weeks. No persiste nt or cumulative effects on neurobehavioral function were found. Body weights and absolute brain weights were reduced in the 8000 ppm group, however there were no differences among groups when brain weight was expressed relative to body weight. No histopathological changes were n oted in the brains or peripheral nervous tissues of MTBE-exposed anima ls. In summary, MTBE produced signs of acute reversible CNS depression following exposure to 8000 ppm and, to a lesser extent, to 4000 ppm v apor. The no-observed-adverse-effect level for these effects was 800 p pm in the present study. No persistent or cumulative neurotoxic effect s were observed following exposure to MTBE at concentrations up to 800 0 ppm for 13 weeks. (C) 1997 John Wiley & Sons, Ltd.