Toxicokinetics and acute effects of MTBE and ETBE in male volunteers

Methyl tertiary butyl ether (MTBE) is widely used in gasoline as an oxygenator and octane enhancer. There is also an interest in using the ethyl tertiary butyl (ETBE) and methyl tertiary amyl (TAME) ethers. we measured the blood, water, and olive oil/air partition coefficients in vitro of MTBE, ETBE, TAME and tertiary butyl alcohol (TEA), a metabolite of MTBE and ETBE. The results indicate similar uptake and distribution behavior Tar the three ethers and a slight affinity for fatty tissues. The partition coefficients of TEA indicate that this metabolite is not excreted via the lungs to any great extent and that it is preferentially distributed in body water. Further, we exposed 10 healthy male volunteers to MTBE vapor at 5, 25 and 50 ppm for 2 h during light physical exercise. Uptake and disposition were studied by measuring MTBE and TEA in inhaled and exhaled air, blood and urine. Low uptake, high post-exposure exhalation, and low blood clearance indicate slow metabolism of MTBE relative to many other solvents. A low recovery of TEA in urine (below 1% of uptake) indicates further metabolism of TEA. The concentration of MTBE and TEA in blood was proportional to exposure level suggesting linear kinetics up to 50 ppm. The half life of 7-10 h in blood and urine indicates that TEA would be more suitable than the parent compound as a biomarker for MTBE exposure. Subjective ratings (discomfort, irritative symptoms, CNS effects) and eye (redness, tear film break-up time, conjunctival damage, blinking frequency) and nose (peak expiratory flow, acoustic rhinometry, inflammatory markers in nasal lavage) measurements indicated no or minimal effects of MTBE.