A data-derived safety (uncertainty) factor for the intense sweetener, saccharin

An increased incidence of bladder cancer is found when male rats are fed high dietary concentrations of sodium saccharin (3% or more) from birth. This toxicity has been used as the basis for the development of a data-derived safety factor. Such an effect would attract an extra factor (10-fold) for nature of toxicity and in the absence of other data would result in a high overall safety factor. However the extensive mechanistic database on sodium saccharin allows an assessment of the potential relevance of the effect for humans. In addition the effect is only seen under specific conditions in rats, i.e. largely with the sodium salt and with a commercial rat diet. The effect is not related to the concentration of saccharin in the rat urine or bladder so that toxicokinetic considerations are simplified. The extensive animal database allows the determination of data-derived factors for inter-species differences in both toxicokinetics and toxicodynamics. Based on this analysis an overall safety factor of 50 (which includes the factor of 10 for severity of effect) would appear appropriate at the present time. This factor, and the ADI which would result from its application, are consistent with the absence of an association between the consumption of artificial sweeteners and bladder cancer in humans.