Experimental exposure to methyl tertiary-butyl ether. I. Toxicokinetics in humans

Methyl tertiary-butyl ether (MTBE) is widely used in gasoline as an oxygenate and octane enhancer. The aim of this study was to evaluate the uptake, distribution, metabolism, and elimination of MTBE in humans. Ten healthy male volunteers were exposed to MTBE vapor (5, 25, and 50 ppm) on three different occasions during 2 h of light physical exercise (50 W). MTBE and the metabolite tertiary-butyl alcohol (TBA) were monitored in exhaled air, blood, and urine. Blood and urine were collected at selected time intervals, during and up to 3 days after the exposure, and analyzed by head space gas chromatography. MTBE in exhaled air was collected with sorbent sample tubes and subsequently analyzed by gas chromatography. The respiratory uptake of MTBE was rather low (42-49%), and the respiratory exhalation was high (32-47%). A relatively low metabolic blood clearance (0.34-0.52 L/h/kg) was seen compared to many other solvents. The kinetic profile of MTBE in blood could be described by four phases, and the average half-lives were 1 min, 10 min, 1.5 h, and 19 h. The post-exposure decay curve of MTBE in urine was separated into two linear phases, with average half-lives of 20 min and 3 h. The average post-exposure half-lives of TBA in blood and urine were 10 and 8.2 h, respectively. The urinary excretion of MTBE and TBA was less than 1% of the absorbed dose, indicating further metabolism of TBA, other routes of metabolism, or excretion. The kinetics of MTBE and TBA were linear up to the highest exposure level of 50 ppm. We suggest that TBA in blood or urine is a more appropriate biological exposure marker for MTBE than the parent ether itself.