SENSORY, SYMPTOMATIC, INFLAMMATORY, AND OCULAR RESPONSES TO AND THE METABOLISM OF METHYL TERTIARY BUTYL ETHER IN A CONTROLLED HUMAN EXPOSURE EXPERIMENT

The Clean Air Act of 1990 mandates that those areas of the country tha t do not attain the health-based National Ambient Air Quality Standard for CO must add oxygenates (2.7% by weight) to auto fuels (oxyfuels). In the fall of 1992, the addition of methyl tertiary butyl ether (MTB E) to automotive fuels coincided with complaints of illness in some pa rts of the country. In Alaska, the reported symptoms included headache , nasal, throat, or ocular irritation, nausea or vomiting, dizziness, and sensations of ''spaciness'' or disorientation. We conducted a cham ber exposure experiment to determine if exposure to pure MTBE would el icit similar responses to those reported to be related to MTBE exposur e. Nineteen male and 18 female subjects were exposed in a repeated-mea sures design to clean air (CA) and 1.39 ppm (5.0 mg/m(3)) MTBE for 1 h . This level was selected to approximate a typical exposure experience d during refueling. Exposures were separated by at least 1 wk. Symptom questionnaires were completed before and during exposure. Cognitive t esting was completed once during exposure. Objective measures of ocula r and nasal irritation were obtained pre- and postexposure. Four quest ions relevant to the reported symptoms, relating to air quality, odor strength, headache, and nasal irritation, were considered confirmatory hypotheses. All other measures were exploratory. The only significant confirmatory result was a difference in rating of CA quality by the f emale subjects as better than during the MTBE exposure. No other measu res, objective or cognitive, approached significance. These results in dicate that in young, healthy subjects a 1-h exposure to 1.39 ppm MTBE does not increase symptom reporting or result in increases in objecti ve biomarkers of inflammation. Two subjects also participated in a stu dy of the pharmacokinetics of MTBE in which blood samples were obtaine d before, during, and at various time points up to 7 h postexposure. M TBE in blood rose rapidly and was metabolized to tertiary butyl alcoho l (TBA), which gradually increased in the blood and maintained an elev ated level for the duration of the sampling.