Biotransformation and kinetics of excretion of tert-amyl-methyl ether in humans and rats after inhalation exposure

tert-Amyl methyl ether (TAME) may be widely used as an additive to gasoline in the future. The presence of this ether in gasoline reduces the tail pip e emission of pollutants. Therefore, widespread human exposure to TAME may occur. To contribute to the characterization of potential adverse effects o f TAME, its biotransformation was compared in humans and rats after inhalat ion exposure. Human volunteers (three males and three females) and rats (fi ve males and five females) were exposed to 4 (3.8 +/- 0.2) and 40 (38.4 +/- 1.7) ppm TAME for 4 h in a dynamic exposure system. Urine samples were col lected for 72 h in 6-h intervals and blood samples were taken at regular in tervals for 48 h in humans. In urine, the TAME metabolites tert-amyl alcoho l (t-amyl alcohol), 2-methyl-2,3-butane diol, 2-hydroxy-2-methylbutyric aci d, and 3-hydroxy-3-methylbutyric acid were quantified. TAME and t-amyl alco hol were determined in blood samples. After the end of the exposure period, blood concentrations of TAME were 4.4 +/- 1.7 mu M in humans and 9.6 +/- 1 .4 mu M in rats after 40 ppm TAME, and 0.6 +/- 0.1 mu M in humans and 1.4 /- 0.8 mu M in rats after 4 ppm. TAME was rapidly cleared from blood in bot h rats and humans. The blood concentrations of t-amyl alcohol were 9.2 +/- 1.8 mu M in humans and 8.1 +/- 1.5 mu M in rats after 40 ppm TAME, and 1.0 +/- 0.3 mu M in humans and 1.8 +/- 0.2 mu M in rats after 4 ppm TAME. t-Amy l alcohol was also rapidly cleared from blood. In urine of humans, 2-methyl -2,3-butane diol, 2-hydroxy-2-methylbutyric acid, and 3-hydroxy-3-methylbut yric acid were recovered as major excretory products in urine. In rats, 2-m ethyl-2,3-butane diol and its glucuronide were major TAME metabolites. t-Am yl alcohol and its glucuronide were minor TAME metabolites in both species. All metabolites of TAME excreted with urine in rats were rapidly eliminate d, with elimination half-lives of lass than 6 h. Metabolite excretion in hu mans was slower and elimination half-lives of the different metabolites wer e between 6 and 40 h in humans. The obtained data indicate differences in T AME biotransformation and excretion between rats and humans. In rats, TAME metabolites are rapidly excreted. In humans, metabolic pathways are differe nt and metabolite excretion is slower. Recovery of TAME metabolites in urin e was higher in humans as compared to rats, suggesting more intensive biotr ansformation of TAME in humans.