Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats

Abstract

Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000ppm (v/v) in whole-body inhalation chambers for 6h/day, 5days/week for 104weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500ppm and above, and mineral deposition was apparent in the renal papilla at 5,000ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.