Saccharin: a toxicological and historical perspective.

Saccharin, first synthesized in 1879, eventually became popular as an inexpensive substitute for sugar, particularly as a non-caloric sweetner. The dispute concerning the safety of saccharin for human consumption is almost as old as saccharin itself. In this article, the history concerning the uses of saccharin and the accompanying controversy are reviewed. In addition, the spectrum of toxicological and epidemiological studies to which saccharin has been subjected are also examined. While the toxicological data indicate that saccharin is probably the agent solely responsible for the bladder tumors observed in second generation male rats, the epidemiological studies provide, at best, an equivocal relationship between the consumption of saccharin and bladder cancer. A benefit-risk evaluation for saccharin showed few, if any documentable benefits from the use of saccharin and much genuine uncertainty concerning the potential risks for ingestion by man. This element of genuine uncertainty as to the extent of human risk posed to man is the crux of saccharin's past and its foreseeable future.