Toxicological Sciences, Vol 51, 108-118, Copyright © 1999 by Society of Toxicology
MA Medinsky, DC Wolf, RC Cattley, B Wong, DB Janszen, GM Farris, GA Wright and JA Bond
The 1990 Clean Air Act Amendments require that oxygenates be added to
automotive fuels to reduce emissions of carbon monoxide and hydrocarbons.
One potential oxygenate is the aliphatic ether ethyl tertiary butyl ether
(ETBE). Our objective was to provide data on the potential toxic effects of
ETBE. Male and female Fisher 344 rats and CD- 1 mice were exposed to 0
(control), 500, 1750, or 5000 ppm of ETBE for 6 h/day and 5 days/wk over a
13-week period. ETBE exposure had no effect on mortality and body weight
with the exception of an increase in body weights of the female rats in the
5000-ppm group. No major changes in clinical pathology parameters were
noted for either rats or mice exposed to ETBE for 6 (rats only) or 13
weeks. Liver weights increased with increasing ETBE-exposure concentration
for both sexes of rats and mice. Increases in kidney, adrenal, and heart
(females only) weights were noted in rats. Degenerative changes in
testicular seminiferous tubules were observed in male rats exposed to 1750
and 5000 ppm but were not seen in mice. This testicular lesion has not been
reported previously for aliphatic ethers. Increases in the incidence of
regenerative foci, rates of renal cell proliferation, and alpha2u- globulin
containing protein droplets were noted in the kidneys of all treated male
rats. These lesions are associated with the male rat- specific syndrome of
alpha2u-globulin nephropathy. Increases in the incidence of centrilobular
hepatocyte hypertrophy and rates of hepatocyte cell proliferation were seen
in the livers of male and female mice in the 5000-ppm group, consistent
with a mitogenic response to ETBE. These two target organs for ETBE
toxicity, mouse liver and male rat kidney, have also been reported for
methyl tertiary butyl ether and unleaded gasoline.
ARTICLES
Effects of a thirteen-week inhalation exposure to ethyl tertiary butyl ether on fischer-344 rats and CD-1 mice
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137, USA.
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