Sweeteners cyclamate

The Delaney Amendment to the Food and Drug Act defined and controlled food additives any additives showing an increase in cancer tumors in rats, even if extremely large doses were used in the animal studies, had to be outlawed in foods recent debates have focused on a number of additives, including the artificial sweetener cyclamate. 

The artificial sweetener cyclamate was banned becanse of its link to bladder cancer in rats fed with large doses 20 snbseqnent studies have failed to confirm this result, but cyclamate remains banned. 

Uses/Sources. Production of rubber-processing chemicals corrosion inhibitor in boiler feed water production of insecticides, plasticizers, and dry cleaning soaps a metabolite of the sweetener cyclamate... 

The artificial sweetener cyclamate was banned because of a study linking it to bladder cancer in rats when large doses were fed. At least 20 subsequent studies have failed to confirm this result but cyclamate remains banned. In 1977 saccharin was found to cause cancer in rats. It was banned by the FDA temporarily, but Congress placed a moratorium on this ban because of public pressure. In 1992 it was found that saccharin may cause cancer in rats but not in humans. Saccharin is still available today. A more recent sweetener, aspartame (Nutrasweef ), has also come under attack but has not been proven to be a problem since its introduction in 1981. 

FE Ahmed, DB Thomas. Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate. CRC Crit Rev Toxicol 22(2) 81-118, 1992. 

With the general name of cyclohexylsulphamate, this sweetener was discovered in 1937 by Michael Sveda at the University of Illinois. The sodium salt is the most commonly used form. It is a white crystalline salt with good solubility. The relative sweetness of cyclamate is comparatively low, at approximately 35, in most food systems (Bakal, 1983). The taste quality of cyclamate as a sole sweetener has a slow onset time and can have a sweet/sour aftertaste at high concentrations (Franta et al., 1986). Sweetness quality is greatly unproved in combination with other sweeteners. Cyclamate is synergistic with acesulfame K (Von Rymon Lipinsky, 1985), aspartame (Searle, 1971), saccharin (Von Rymon Lipinsky, 1987) and sucralose (Tate Lyle Pic, 2002). 

Cyclamate is stable under conditions likely to be encountered in soft drinks, that is, pH range 2-7, pasteurisation and UHT treatments. Analysis is usually using HPLC. Owing to differences in chemistry between cyclamate and other intense sweeteners, cyclamate requires derivatisation before analysis by HPLC (MacArthur et al., 2002). 

The artificial sweetener cyclamate is first introduced to the market by Abbot Laboratories under the name Sucaryl. It does not have saccharin s aftertaste... 

The connection between the sweetener cyclamate and false positive amphetamine results is discussed in [54],... 

Lamberg SI (1967) A new photosensitizer. The artificial sweetener cyclamate. JAMA 201 747-750... 

Stanley Thompson, and Kenneth Street discover the element californium. Acrylic fiber invented. Artificial sweetener cyclamate is marketed. It is later discovered to cause cancer and is banned in the United States in 1970. 

Other Sweeteners. Two other sweeteners, sucralose and cyclamates, are approved for use outside of the United States. Sucralose, a chlorinated derivative of sucrose which is 500—600 times as sweet as sugar, has received limited approval in Canada, and petitions for its approval are pending in the United States and Europe (71). Cyclamate sweeteners, once available in the United States, but now baimed because they caused bladder cancer in animals, are stiU available in Canada and Europe. Table 7 gives several examples of nonnutritive sweeteners that have been developed. 

Before a 1/1 /70 FDA ban (rescission proposed in early 1990), cyclamate noncaloric sweeteners were the major derivatives driving cycloliexylamine production. The cyclohexylsulfamic acid sodium salt (39) [139-05-9J and mote thermally stable calcium cyclohexylsulfamic acid (40) [139-06-1] salts were prepared from high purity cyclohexylamine by, among other routes, a reaction cycle with sulfamic acid. 

Sucrose occupies a unique position in the sweetener market (Table 3). The total market share of sucrose as a sweetener is 85%, compared to other sweeteners such as high fmctose com symp (HFCS) at 7%, alditols at 4%, and synthetic sweeteners (aspartame, acesulfame-K, saccharin, and cyclamate) at 4%. The world consumption of sugar has kept pace with the production. The rapid rise in the synthetic sweetener market during 1975—1995 appears to have reached a maximum. 

In 1969, a chronic toxicity study on a cyclamate saccharin (10 1) blend indicated bladder cancer problems in rats. Cyclamate was soon banned by the FDA, but saccharin remained an approved sweetener. In 1977, the FDA proposed a ban on saccharin because of the discovery of bladder tumors in some male rats fed with high doses of saccharin. Because no other nonnutritive sweetener was available at that time, the proposed ban faced strong opposition. 

Saccharin imparts a sweetness that is pleasant at the onset but is followed by a lingering, bitter aftertaste. Sensitivity to this bitterness varies from person to person. At high concentration, however, most people can detect the rather unpleasant aftertaste. Saccharin is synergistic with other sweeteners of different chemical classes. For example, saccharin—cyclamate, saccharin—aspartame, saccharin—sucralose, and saccharin—aUtame combinations all exert synergy to various degrees. The blends, as a rule, exhibit less aftertaste than each of the component sweeteners by themselves. 

Abbott Laboratories, which has conducted additional toxicity and carcinogenicity studies with cyclamate, a 10 1 mixture of cyclamate—saccharin, and cyclohexylamine, claimed to be unable to confirm the 1969 findings. Abbott then filed a food additive petition for cyclamate in 1973, which was denied by the FDA in 1980. In 1982, the Calorie Control Council and Abbott Laboratories filed a second food additive petition containing the results of additional safety studies (73). That petition was stiU pending as of 1996. Cyclamate is, however, allowed for use in any or all three categories, ie, food, beverage, and tabletop, in about 50 countries. Sweet n Low, known in the United States as a saccharin-based table-top sweetener, contains exclusively cyclamate in Canada. 

To meet consumer demands, manufacturers are developing new nonnutritive sweeteners that more closely match the taste and mouthfeel of sucrose. There are several nonnutritive sweeteners currentiy pending FDA approval for use in soft drinks. They include sucralose [56038-13-2] aUtame [80863-62-3] encapsulated aspartame, cyclamates, and acesulfame-K [55589-62-3] also known as paUtinit. 

The concentration of the flavor in the dentifrice and the nature of substances added to bring out specific flavor notes and thereby make the flavor unique are significant concerns. The flavor must not be excessive it must not bum too strongly. Also, the flavor must not be a sensitizer. Synthetic sweeteners are usually added, although regulatory concerns limit their selection for example, cyclamate [100-88-9] is not used in the United States. 

Examine the structures oisucrose, the natural sweetener, and saccharin, sodium cyclamate and aspartame (Nutrasweet), three of the most common artificial sweeteners. What, if any, structural features do these molecules have in common Compare electrostatic potential maps for the different sweeteners. Are there any significant features in common Based on yom findings, do you think it is likely that entirely different artifical sweeteners might be discovered Explain. 

Its freely water-soluble calcium salt (patented 1957) was a much-used and very effective sweetener, as was the sodium salt, whose sweetness was first noted in 1937 cyclamic acid is ineffective as it is essentially insoluble in aqueous media. 

Cyanuric chloride method, for covalent ligand immobilization, 6 396t Cycads, in nitrogen fixation, 2 7 300 Cyclamate, 22 42 24 234, 236 sweeteners, 2 513-514 Cyclamen aldehyde, aroma chemical derived from toluene, 3 234 Cyclams, 24 41—42... 

Sweeteners can be roughly divided into two groups bulk and intense sweeteners. Prodolliet (1996) and Gloria (2000) reviewed thoroughly the analysis and properties of intense sweeteners acesulfame-K, alitame, cyclamate, aspartame, glycyrrhizin, neohesperidin DC, saccharin, stevioside, sucralose and thaumatin. They are generally used in low calorie products such as diet... 

This technique has been established for many years particularly for water, soil and feeding-stuff analysis, where a large number of analyses are required for quality control or monitoring purposes. A number of applications have been published for food additives including aspartame (Fatibello et al., 1999), citric acid (Prodromidis et al., 1997), chloride, nitrite and nitrate (Ferreira et al., 1996), cyclamates (Cabero et al., 1999), sulphites (Huang et al., 1999 AOAC Int, 2000), and carbonate, sulphite and acetate (Shi et al., 1996). Yebra-Biumm (2000) reviewed the determination of artificial sweeteners (saccharin, aspartame and cyclamate) by flow injection. 

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