Morphologic changes in the urinary bladder and stomach after long-term administration of sodium saccharin in F344 rats.

The effects of long-term administration of sodium saccharin on the urinary bladder and stomach of F344 rats were investigated. Sixty-eight male F344 rats, aged 7 weeks at the beginning of the experiment, were maintained on diet supplemented with 5% sodium saccharin for 112 weeks. Animals were killed periodically and investigated for gross and microscopic lesions in the urinary bladder and stomach. Papillary or nodular hyperplasia was evident in the urinary bladder epithelium from 8 weeks onwards although no papillomas or transitional cell carcinomas developed. Lesions observed in the bladders of control animals fed the basal diet without the saccharin supplement were limited throughout the experiment to a few areas of simple hyperplasia. While no changes were apparent in the stomach of control animals, a 100% incidence of hyperkeratosis at the limiting ridge of the forestomach was observed after 80 weeks administration of saccharin, 5 of 20 animals also having papillomas. Furthermore, erosion was pronounced in the glandular stomach of saccharin-treated animals with 4 cases of atypical gland being observed. No histopathological lesions were apparent in the liver, kidneys or spleen of either control or experimental groups.