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Infobox disclaimer and references
Saccharin is an artificial sweetener. The basic substance, benzoic sulfinide, has effectively no food energy and is much sweeter than sucrose, but has an unpleasant bitter or metallic aftertaste, especially at high concentrations. In countries where saccharin is allowed as a food additive, it is used to sweeten products such as drinks, candies, medicines, and toothpaste.
Saccharin is unstable when heated but it does not react chemically with other food ingredients, and it stores well. Blends of saccharin with other sweeteners are often used to compensate for each sweetener's weaknesses. A 10:1 cyclamate:saccharin blend is common in countries where both these sweeteners are legal; in this blend, each sweetener masks the other's off-taste. Saccharin is often used together with aspartame in diet soda, so that some sweetness remains should the fountain syrup be stored beyond aspartame's relatively short shelf life. Saccharin is believed to be an important discovery, especially for diabetics, as it goes directly through the human digestive system without being digested. Although saccharin thus has no food energy, it can trigger the release of insulin in rats, apparently as a result of its taste. 
In its acid form, saccharin is not water-soluble. The form used as an artificial sweetener is usually its sodium salt. The calcium salt is also sometimes used, especially by people restricting their dietary sodium intake. Both salts are highly water-soluble: 0.67 grams per milliliter water at room temperature.
Saccharin was first produced in 1878 by Constantin Fahlberg, a chemist working on coal tar derivatives in Ira Remsen's laboratory at the Johns Hopkins University, and it was Fahlberg who, accidentally, discovered its intensely sweet nature. Fahlberg and Remsen published articles on benzoic sulfinide in 1879 and 1880. In 1884, now working on his own in New York City, Fahlberg applied for patents in several countries describing methods of producing this substance that he named saccharin. Fahlberg would soon grow wealthy, while Remsen merely grew irate, believing that he deserved credit for substances produced in his laboratory. On the matter, Remsen commented, "Fahlberg is a scoundrel. It nauseates me to hear my name mentioned in the same breath with him."
Although saccharin was commercialized not long after its discovery, it was not until sugar shortages during World War I that its use became widespread. Its popularity further increased during the 1960s and 1970s among dieters, since saccharin is a calorie-free sweetener. In the United States saccharin is often found in restaurants in pink packets; the most popular brand is "Sweet'N Low". A small number of soft drinks are sweetened with saccharin, the most popular[How to reference and link to summary or text] being the Coca-Cola Company's cola drink Tab, introduced in 1963 as a diet cola soft drink.
Saccharin has the chemical formula C7H5NO3S and it can be produced in various ways. The original route starts with toluene, but yields from this starting point are low. In 1950, an improved synthesis was developed at the Maumee Chemical Company of Toledo, Ohio. In this synthesis, anthranilic acid successively reacts with nitrous acid, sulfur dioxide, chlorine, and then ammonia to yield saccharin. Another route begins with o-chlorotoluene.
Starting in 1907, the USDA began investigating saccharin. Problems with saccharin and the USDA have not been resolved since then. The initial series of investigations begun by the USDA in 1907 was a direct result of the Pure Food and Drug Act. This act was passed in 1906 in the wake of a storm of health controversies concerning the meat-packing industry.
Harvey Wiley was one particularly well-known figure involved in the investigation of saccharin. Wiley, then the director of the bureau of chemistry for the USDA, had suspected saccharin to be damaging to human health. Wiley first battled saccharin in 1908. In a clash that epitomizes the controversial history of saccharin, Harvey told then President Theodore Roosevelt directly that "Everyone who ate that sweet corn was deceived. He thought he was eating sugar, when in point of fact he was eating a coal tar product totally devoid of food value and extremely injurious to health." In a heated exchange, Roosevelt angrily answered Harvey by stating "Anybody who says saccharin is injurious to health is an idiot." In 1911, the Food Inspection Decision 135 stated that foods containing saccharin were adulterated. However in 1912, Food Inspection Decision 142 stated that saccharin was not harmful. The government's stance on saccharin has continued to waver ever since. More controversy was stirred in 1969 with the discovery of files from the Food and Drug Administration's investigations of 1948 and 1949. These investigations, which had originally argued against saccharin use, were shown to prove little about saccharin being harmful to human health. In 1972 the USDA made an attempt to completely ban the substance. However, this attempt was unsuccessful and the sweetener remains widely available in the United States; it is the third-most popular after sucralose and aspartame. Cyclamate, however, was banned in the US and saccharin was banned in Canada, leading to different product formulations being marketed in these countries.
In the European Union saccharin is also known by the E number (additive code) E954.
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Throughout the 1960s, various studies suggested that saccharin might be an animal carcinogen. Concern peaked in 1977, after the publication of a study indicating an increased rate of bladder cancer in rats fed large doses of saccharin. In that year, Canada banned saccharin while the United States Food and Drug Administration also proposed a ban. At the time, saccharin was the only artificial sweetener available in the U.S., and the proposed ban met with strong public opposition, especially among diabetics. Eventually, the U.S. Congress placed a moratorium on the ban, requiring instead that all saccharin-containing foods display a warning label indicating that saccharin may be a carcinogen.
Many studies have since been performed on saccharin, some showing a correlation between saccharin consumption and increased frequency of cancer in rats (especially bladder cancer) and others finding no such correlation. No study has ever shown a clear causal relationship between saccharin consumption and health risks in humans at normal doses, though some studies have shown a correlation between consumption and cancer incidence. Some of the animal studies were procedurally flawed. According to tradegroup-operated saccharin.org, "Concerns over saccharin's safety were first raised twenty years ago after a flawed study that administered huge quantities of the sweetener to laboratory rats produced bladder tumors in rats. New and better scientific research has decisively shown that the earlier rat studies are not at all applicable to humans." The U.S. National Institute for Environmental Health Sciences came to the same conclusion in 2000, recommending that saccharin be removed from the list of known or suspected human carcinogens. The mechanism appears to be due the way that rats metabolize sodium, and bladder cancer which cannot be replicated in mammals has also been observed with rat consumption of other sodium salts such as sodium citrate and bicarbonate.
In 1991, after fourteen years, the FDA formally withdrew its 1977 proposal to ban the use of saccharin, and in 2000, the U.S. Congress repealed the law requiring saccharin products to carry health warning labels.
Notes and references
- Paul M. Priebe and George B. Kauffman, “Making Government Policy under Conditions of Scientific Uncertainty: a Century of Controversy about Saccharin in Congress and the Laboratory,” Minerva, 18, 1980, 556-74.
- Novel 1984, by George Orwell, Saccharin is referred to as "saccharine" in the book, however they are referring to the artificial sweetner.
- The word saccharin (as above) has no final "e". The word saccharine, with a final "e", is much older and is an adjective meaning "sugary" – its connection with sugar means the term is used metaphorically, often in a derogative sense, to describe something "unpleasantly over-polite" or "overly sweet". Both words are derived from the Greek word σάκχαρον (sakcharon, German "ch" sound), which ultimately derives from Sanskrit for sugar, sharkara (शर्करा), which literally means "gravel" 
- E Ionescu, F Rohner-Jeanrenaud, J Proietto, RW Rivest and B Jeanrenaud (1988). Taste-induced changes in plasma insulin and glucose turnover in lean and genetically obese rats. Diabetes 37: 773–779.
- H. R. Berthoud, E. R. Trimble, E. G. Siegel, D. A. Bereiter and B. Jeanrenaud (1980). Cephalic-phase insulin secretion in normal and pancreatic islet-transplanted rats. American Journal of Physiology-Endocrinology and Metabolism 238 (4): E336=E340.
- Remsen, I. and Fahlberg, C., (1879). Über die Oxydation des Orthotoluolsulfamids. Chemische Berichte 12: 469–473.
- P. M. Priebem, G. B. Kauffman (1980). Making governmental policy under conditions of scientific uncertainty: A century of controversy about saccharin in congress and the laboratory. Minerva 18 (4): 556–574.
- David J. Ager, David P. Pantaleone, Scott A. Henderson, Alan R. Katritzky, Indra Prakash, D. Eric Walters (1998). Commercial, Synthetic Nonnutritive Sweeteners. Angewandte Chemie International Edition 37 (13-24): 1802–1817.
- Bungard, 1967
- WHO food additives series 17
- pKa data compiled by R. Williams
- Sugasawa, S.; Abe, K. J. Pharm. Soc. Jpn. 1952, 72, 270; Chem Abstr, 1953, 47, 1626c
- Junod, Suzanne. Sugar: A Cautionary Tale. Update Magazine, USFDA, 7-8, 2003. http://www.fda.gov/oc/history/makinghistory/sugar.html
- Preibe and Kauffman, 2,3,4,6,7
- Weihrauch M. R., Diehl V. (2004). Artificial sweeteners - do they bear a carcinogenic risk?. Annals of Oncology 15 (10): 1460–1465.
- Saccharin and Its Salts, International Agency for Research on Cancer
- (no byline) (2000-05-16). U.S. Report Adds to List of Carcinogens. New York Times.
- Chappel CI (June 1994). Saccharin revisited. West. J. Med. 160 (6): 583–5.
Template:E number infobox 950-969
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