Studies were made on the dose response of
saccharin in the induction of bladder lesions. Inbred F344 rats of both sexes were pretreated with 100 ppm
N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the
drinking water for 4 weeks.
Sodium saccharin was given at 50,000, 10,000, 2,000, and 400 ppm in the diet for 32 weeks after BBN administration, and surviving rats were killed at the end of week 36 of the experiment. No increase in incidence of
papilloma or
cancer was noted in either sex at any dose of
saccharin after BBN as compared to levels induced by BBN alone. The incidences of two types of
hyperplasia and average number of papillary or nodular
hyperplasias per 10 cm of basement membrane were significantly increased in the group receiving 50,000 ppm
saccharin as compared to the group given BBN only. None of the incidences or numbers of these lesions were significantly different in any of the other
saccharin-treated groups when compared to the group treated with BBN alone except for the incidences of two types of
hyperplasias in the female rats dosed with 10,000 ppm
saccharin. Dose-response curves showed enhanced hyperplastic responses in both sexes given 2,000--50,000 ppm
saccharin. Administration of various doses of
saccharin without BBN did not cause any changes in the urinary bladders of rats of either sex. These results show that
saccharin enhances the induction of early-stage bladder lesions and that the
biologic response demonstrates a dose-response effect.