Toxicokinetics of human exposure to methyl tertiary-butyl ether (MTBE) following short-term controlled exposures

Methyl tertiary-butyl ether (MTBE) is an oxygenated compound added to gasoline to improve air quality as part of the US Federal Clean Air Act. Due to the increasing and widespread use of MTBE and suspected health effects, a controlled, short-term MTBE inhalation exposure kinetics study was conducted using breath and blood analyses to evaluate the metabolic kinetics of MTBE and its metabolite, tertiary-butyl alcohol (TBA), in the human body. In order to simulate common exposure situations such as gasoline pumping, subjects were exposed to vapors from MTBE in gasoline rather than pure MTBE. Six subjects (three females, three males) were exposed to 1.7 ppm of MTBE generated by vaporizing 15 LV% MTBE gasoline mixture for 15 min. The mean percentage of MTBE absorbed was 65.8±5.6% following exposures to MTBE. The mean accumulated percentages expired through inhalation for 1 and 8 h after exposure for all subjects were 40.1% and 69.4%, respectively. The three elimination half-lives of the triphasic exponential breath decay curves for the first compartment was 1–4 min, for the second compartment 9–53 min, and for the third compartment 2–8 h. The half-lives data set for the breath second and blood first compartments suggested that the second breath compartment rather than the first breath compartment is associated with a blood compartment. Possible locations for the very short breath half-life observed are in the lungs or mucous membranes. The third compartment calculated for the blood data represent the vessel poor tissues or adipose tissues. A strong correlation between blood MTBE and breath MTBE was found with mean blood-to-breath ratio of 23.5. The peak blood TBA levels occurred after the MTBE peak concentration and reached the highest levels around 2–4 h after exposures. Following the exposures, immediate increases in MTBE urinary excretion rates were observed with lags in the TBA excretion rate. The TBA concentrations reached their highest levels around 6–8 h, and then gradually returned to background levels around 20 h after exposure. Approximately 0.7–1.5% of the inhaled MTBE dose was excreted as unchange urinary MTBE, and 1–3% was excreted as unconjugated urinary TBA within 24 h after exposure.