Unexpected sudden deaths of F344 rats in long-term toxicity studies: relationship between sudden deaths and stomach tube material or feed type.

Sudden deaths of F344 rats (F344/Du Crj (Fischer)) have occurred frequently in the late stage of carcinogenicity studies using stomach tubes. To reduce the sudden deaths, the incidence of sudden deaths was compared in the control groups from 104-week carcinogenicity studies using two different stomach tubes (metal and Teflon) and feeds (pellet and powder). The results indicate that replacing metal tubes with Teflon tubes from the first administration or after week 41 of administration was not effective in reducing the sudden deaths. On the other hand, sudden deaths did not occur at all after changing the feed from pellets to powder after week 44 or 79 of administration. In addition, although decreased body weight and retention of feed in the oral, pharyngeal and laryngeal cavities were observed in the animals that died suddenly, there were no abnormalities in histopathological examination. Therefore, it is suggested that changing the feed from pellets to powder should be effective in reducing the sudden deaths of F344 rats in long-term oral gavage studies or carcinogenicity studies.