Controlled ethyl tert-butyl ether (ETBE) exposure of male volunteers - I. Toxicokinetics

Ethyl tert-butyl ether (ETBE) might replace methyl tert-butyl ether (MTBE), a widely used additive in unleaded gasoline. The aim of this study was to evaluate uptake and disposition of ETBE, and eight healthy male volunteers were exposed to ETBE vapor (0, 5, 25, and 50 ppm) during 2 h of light physi cal exercise. ETBE and the proposed metabolites tert-butyl alcohol (TBA) an d acetone were analyzed in exhaled air, blood, and urine. Compared to a pre vious MTBE study (A. Nihlen et al., 1998b, Toxicol. Appl. Pharmacol, 148, 2 74-280) lower respiratory uptake of ETBE (32-34%) was seen as well as a sli ghtly higher respiratory exhalation (45-50% of absorbed ETBE). The kinetic profile of ETBE could be described by four phases in blood (average half-ti mes of 2 min, 18 min, 1.7 h, and 28 h) and two phases in urine (8 min and 8 .6 h). Postexposure half-times of TEA in blood and urine were on average 12 and 8 h, respectively. The 48-h pulmonary excretion of TEA accounted for 1 .4-3.8% of the absorbed ETBE, on an equimolar basis. Urinary excretion of E TBE and TEA was low, below 1% of the ETBE uptake, indicating further metabo lism of TEA or other routes of metabolism and elimination. The kinetics of ETBE and TEA were linear up to 50 ppm. Based upon blood profile, levels in blood and urine, and kinetic profile we suggest that TEA is a more appropri ate biomarker for ETBE than the parent ether itself. The acetone level in b lood was higher after ETBE exposures compared to control exposure, and acet one is probably partly formed from ETBE. (C) 1998 Society of Toxicology.