Effects of a thirteen-week inhalation exposure to ethyl tertiary butyl ether on Fischer-344 rats and CD-1 mice

The 1990 Clean Air Act Amendments require that oxygenates be added to autom otive fuels to reduce emissions of carbon monoxide and hydrocarbons. One po tential 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 per iod. ETBE exposure had no effect on mortality and body weight with the exce ption of an increase in body weights of the female rats in the 5000-ppm gro up. 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 rat s 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 alipha tic ethers, Increases in the incidence of regenerative foci, rates of renal cell proliferation, and alpha(2u)-globulin containing protein droplets wer e noted in the kidneys of all treated male rats. These lesions are associat ed with the male rat-specific syndrome of alpha(2u)-globulin nephropathy, I ncreases in the incidence of centrilobular hepatocyte hypertrophy and rates of hepatocyte cell proliferation were seen in the livers of male and femal e 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 gaso line.