Sodium saccharin was not carcinogenic for the urinary bladder in several one-generation studies in male and female rats or in mice. Calcium saccharin did not produce tumours in one study in male rats. A few studies with sodium saccharin in hamsters and guinea-pigs also showed no induction of bladder tumours but were considered inadequate. Sodium saccharin has been studied in numerous experiments in adult rats involving administration concurrently or, more frequently, sequentially with other chemicals or treatments. Enhanced bladder tumorigenesis has been observed after prior treatment with known urinary bladder carcinogens.
Excretion occurs relatively rapidly with no evidence of accumulation.
The strong nucleophilic character of the saccharin anion and the lack of metabolism are consistent with the lack of DNA reactivity. The urinary concentration of the saccharin anion is similar, regardless of the form administered. Sodium saccharin has been shown to enhance urothelial cell proliferation in rats, primarily in males, resulting in hyperplasia. This regenerative cell proliferation follows urothelial cytotoxic effects. Sodium saccharin at doses that enhance cell proliferation in rats does not do so in other species, including mice, hamsters and guinea-pigs.