Safety of saccharin

Saccharin has been the focus of controversy nearly since its initial synthesis in 1879 by Fahlberg and Remsen. Its primary use has been as a non-caloric synthetic sweetener, but it is also being used commercially for a variety of other purposes including as an antiseptic, preservative, nickelplating, antistatic agent, and numerous other uses. It is an inexpensive, extremely stable chemical that is resistant to heat. Numerous toxicological effects have been attributed to saccharin, dating to its initial proposed use as a sweetener. There is the famous quote by President Theodore Roosevelt in response to being told that saccharin was “injurious to health” by Dr. Harvey W. Wiley of the US Department of Agriculture: “You tell me that saccharin is injurious to health? Why my doctor gives it to me everyday. Anybody who says saccharin is injurious to health is an idiot”. Most of the various accusations regarding the toxicity of saccharin were addressed over the years, with its commercial use continuing. In 1970 a new controversy swirled around the use of saccharin as an artificial sweetener with the discovery that it produced bladder cancer when administered to rats in a twogeneration bioassay. Significant concern ensued that it might also pose a cancer risk to humans. Addressing this controversy has extended the limits of toxicological testing and mechanistic considerations, with results not only influencing the decision regarding saccharin but also setting precedence for numerous other chemicals in various settings, not just food additives. For a history of saccharin, including the more recent controversy involving bladder cancer, the readers are encouraged to read several reviews on the subject (1-4). Animal testing is the foundation for toxicological screening of chemicals for nearly all uses, including food additives. There are two basic assumptions when using animal models for such screening (2, 5): 1) the toxic effect produced in the test species will also occur in humans (species extrapolation); and 2) the effect seen at the doses used in the screening evaluation are relevant to the levels to which humans are exposed (dose extrapolation). For many chemicals and toxic endpoints, these assumptions are reasonable. However, it is only with mechanistic understanding that one can address either of these assumptions. For the influence of saccharin on the bladder in rats, based on extensive mechanistic research, neither of these assumptions were found to be valid. It is a rat specific phenomenon and it only occurs at extremely high doses (25,000 ppm of the diet and higher). SACCHARIN CARCINOGENICITY STUDIES