Toxicological Sciences, Vol 51, 1-8, Copyright © 1999 by Society of Toxicology
A Amberg, E Rosner and W Dekant
Methyl-tert-butyl ether (MTBE) is widely used as an additive to gasoline to
increase oxygen content and reduce tail pipe emission of pollutants.
Therefore, widespread human exposure may occur. To contribute to the
characterization of potential adverse effects of MTBE, its
biotransformation was compared in humans and rats after inhalation
exposure. Human volunteers (3 males and 3 females) and rats (5 each, males
and females) were exposed to 4 (4.5 +/- 0.4) and 40 (38.7 +/- 3.2) ppm MTBE
for 4 h in a dynamic exposure system. Urine samples from rats and humans
were collected for 72 h in 6-h intervals, and blood samples were taken in
regular intervals for 48 h. In urine, MTBE and the MTBE metabolites
tertiary-butanol (t-butanol), 2-methyl- 1,2-propane diol, and
2-hydroxyisobutyrate were quantified; MTBE and t- butanol were determined
in blood samples. After the end of the exposure period, inhalation of 40
ppm MTBE resulted in blood concentrations of MTBE 5.9 +/- 1.8 microM in
rats and 6.7 +/- 1.6 microM in humans. The MTBE blood concentrations after
inhalation of 4 ppm MTBE were 2.3 +/- 1.0 in rats and 1.9 +/- 0.4 microM in
humans. MTBE was rapidly cleared from blood with a half-life of 2.6 +/- 0.9
h in humans and 0.5 +/- 0.2 h in rats. The blood concentrations of
t-butanol were 21.8 +/- 3.7 microM in humans and 36.7 +/- 10.8 microM in
rats after 40 ppm MTBE, and 2.6 +/- 0.3 in humans and 2.9 +/- 0.5 in rats
after 4 ppm MTBE. In humans, t-butanol was cleared from blood with a
half-life of 5.3 +/- 2.1 h. In urine samples from controls and in samples
collected from the volunteers and rats before the exposure, low
concentrations of t- butanol, 2-methyl-1,2-propane diol and
2-hydroxyisobutyrate were present. In urine of both humans and rats exposed
to MTBE, the concentrations of these compounds were significantly
increased. 2- Hydroxyisobutyrate was recovered as a major excretory product
in urine; t-butanol and 2-methyl-1,2-propane diol were minor metabolites.
All metabolites of MTBE excreted with urine were rapidly eliminated in both
species after the end of the MTBE exposure. Elimination half-lives for the
different urinary metabolites of MTBE were between 7.8 and 17.0 h in humans
and 2.9 to 5.0 h in rats. The obtained data indicate that MTBE
biotransformation and excretion are similar in rats and humans, and MTBE
and its metabolites are rapidly excreted in both species. Between 35 and
69% of the MTBE retained after the end of the exposure was recovered as
metabolites in urine of both humans and rats.
ARTICLES
Biotransformation and kinetics of excretion of methyl-tert-butyl ether in rats and humans
Institut fur Toxikologie, Universitat Wurzburg, Germany.
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