Liquid/air partition coefficients of methyl and ethyl T-butyl ethers, T-amyl methyl ether, and T-butyl alcohol

Partition coefficients are essential to a description of the uptake and distribution of volatile substances in humans and in the development of physiologically based pharmacokinetic models. Liquid/air partition coefficients (lambda) of three ethers, methyl t-butyl ether (MTBE), ethyl t-butyl ether (ETBE), and t-amyl methyl ether (TAME) were determined in vitro by head space-gas chromatography. These ethers, and especially MTBE, are used in unleaded gasoline to enhance the oxygen and octane content, and to reduce the output of carbon monoxide during combustion. Partition coefficients of t-butyl alcohol (TBA), a metabolite of MTBE, were determined also. The liquids tested were fresh human blood, water (physiological saline), and olive oil. The (lambda)blood/air values were: 17.7 (95% confidence interval 17.0-18.4) for MTBE; 11.7 (11.3-12.1) for ETBE; and 17.9 (17.3-18.5) for TAME. Corresponding (lambda)water/air values were 15.2 (14.9-15.5), 8.39 (8.19-8.59), and 11.9 (11.7-12.1). The ethers have a higher affinity for oil, the values for (lambda)oil/air being 120 (114-125), 190 (183-197), and 337 (320-354), respectively. As expected, the (lambda)blood/air and (lambda)water/air for TBA were much higher than for the ethers, 462 (440-484) and 603 (590-617), respectively. The (lambda)oil/air was 168 (161-174) for TBA. The interindividual variability of the (lambda)blood/air (10 subjects) was calculated as the coefficient of variation, and estimated as: 14% for MTBE, 20% for ETBE, 20% for TAME, and 30% for TBA. No significant difference was seen in the (lambda)blood/air between the sexes.