Saccharin , carcinogen risk

International Agency for Research on Cancer (lARC) (1999) Saccharin and its salts. Monographs on the Evaluation of the Carcinogenic Risks to Humans 73 517-624. 

Hie artificial sweetener, saccharin, and the secondary mold product, aflatoxin Bj, are present in many foods consumed by humans. Both chemicals produce cancer in rats. For this reason, they have aroused concern among scientists and the public as to the carcinogenic risk that they pose to humans. A comparison of these two chemicals reveals striking contrasts in potency, metabolism, mechanism-of-action, and experimental approach to assessing metabolism. These contrasts are examined in detail to illustrate the importance of metabolism in safety evaluation. 

It is recommended that daily saccharin intake be maintained below 1 g because of a risk of bladder cancer. A lifetime daily diet containing 5-7.5% saccharin has induced bladder tumors in rats [69]. However, it is probable that saccharin is only a very weak carcinogen in humans. The amount contained in pharmaceutical preparations is well below the recommended maximum human daily intake. 

During the discussions of a potential carcinogenicity of saccharin, contaminants, especially o-toluene sulphonamide, were blamed for the toxicological effects observed in these studies. The studies carried out on such contaminants which in former times occurred in concentrations well exceeding 1000 ppm, did, however, not reveal any such effects, and the observed effects today are believed to be saccharin-specific. In order to minimise risks for consumers, low maximum levels for these products were introduced into the specifications. 

If the dose-response curves for the two sample carcinogens are reexamined, it can be seen that response axes represent the fraction of animals that developed extra tumors at particular sites - the bladder in the case of saccharin, and the liver in that of aflatoxin - over their lifetimes of exposure. Another term for this fraction is lifetime risk — the lifetime probability that the specific tumors develop. Each animal in a treatment group was at a certain risk of developing tumors because of the chemical exposure the size of that risk is represented by the measured tumor rate (ignoring the variability inherent in all experimental studies). At some point, below lifetime risks of about 5-10% (1 in 20 to 1 in 10), the experiments lost capacity to detect excess tumor responses. But under the no-threshold hypothesis risks continue to exist at all doses, even if they can not be detected in animal experiments, and disappear completely only when the dose goes to zero. 

The first artificial sweetener to be used extensively was saccharine, which is used commonly as its more soluble sodium salt. Saccharine is about 300 times sweeter than sucrose. The discovery of saccharine was hailed as a great benefit for diabetics because it could be used as an alternative to sugar. As a pure substance, the sodium salt of saccharine has a very intense sweet taste, with a somewhat bitter aftertaste. Because it has such an intense taste, it can be used in very small amounts to achieve the desired effect. In some preparations, sorbitol is added to ameliorate the bitter aftertaste. Prolonged studies on laboratory animals have shown that saccharine is a possible carcinogen. In spite of this health risk, the government has permitted saccharine to be used in foods that are primarily intended to be used by diabetics. 

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