Name: Sodium Cyclamate
CAS No: Sodium N-cyclohexylsulfamate [139-05-9]
BP: Sodium Cyclamate PhEur: Sodium Cyclamate
Cyclamate sodium; cyclohexylsulfamic acid monosodium salt; E952; natrii cyclamas; sodium cyclohexanesulfamate.
Sodium N-cyclohexylsulfamate [139-05-9]
C6H12NNaO3S 201.22
Sodium cyclamate is used as an intense sweetening agent in pharmaceutical formulations, foods, beverages, and table-top sweeteners. In dilute solution, up to about 0.17% w/v, the sweetening power is approximately 30 times that of sucrose. However, at higher concentrations this is reduced and at a concentration of 0.5% w/v a bitter taste becomes noticeable. Sodium cyclamate enhances flavor systems and can be used to mask some unpleasant taste characteristics. In most applications, sodium cyclamate is used in combination with saccharin, often in a ratio of 10 : 1.(1)
Sodium cyclamate occurs as white, odorless or almost odorless crystals, or as a crystalline powder with an intensely sweet taste.
See Table I
Acidity/alkalinity pH = 5.5–7.5 for a 10% w/v aqueous solution. NIR spectra see Figure 1. Solubility see Table II.
Sodium cyclamate is hydrolyzed by sulfuric acid and cyclohexylamine at a very slow rate that is proportional to the hydrogen ion concentration. Therefore, for all practical considerations, it can be regarded as stable. Solutions are also stable to heat, light, and air over a wide pH range Samples of tablets containing sodium cyclamate and saccharin have shown no loss in sweetening power following storage for up to 20 years. The bulk material should be stored in a well-closed container in a cool, dry place.
Cyclamates are prepared by the sulfonation of cyclohexylamine in the presence of a base. Commercially, the sulfonation can involve sulfamic acid, a sulfate salt, or sulfur trioxide. Tertiary bases such as triethylamine or trimethylamine may be used as the condensing agent. The amine salts of cyclamate that are produced are converted to the sodium, calcium, potassium, or magnesium salt by treatment with the appropriate metal oxide.
There has been considerable controversy concerning the safety of cyclamate following the FDA decision in 1970 to ban its use in the USA.(2–4) This decision resulted from a feeding study in rats that suggested that cyclamate could cause an unusual form of bladder cancer. However, that study has been criticized because it involved very high doses of cyclamate administered with saccharin, which has itself been the subject of controversy concerning its safety; see Saccharin. Although excreted almost entirely unchanged in the urine, a potentially harmful metabolite of sodium cyclamate, cyclohexylamine, has been detected in humans.(5) In addition, there is evidence to suggest cyclamate is metabolized to cyclohexylamine by the microflora in the large intestine of some individuals (approximately 25% of the population with higher precedence in Japanese than Europeans or North Americans). Cyclohexylamine, following absorption, is metabolized to an extent of 1-2% to cyclohexanol and cyclohexane-1,2-diol. Established no-observedeffect level (NOEL) and acceptable daily intake (ADI) values are based on cyclohexylamine levels of high cyclamate converters.(6,7) Extensive long-term animal feeding studies and epidemiological studies in humans have failed to show any evidence that cyclamate is carcinogenic or mutagenic.(8,9) As a result, sodium cyclamate is now accepted in many countries for use in foods and pharmaceutical formulations. See also Section 16. Few adverse reactions to cyclamate have been reported, although its use has been associated with instances of photosensitive dermatitis.(10) The WHO has set an estimated acceptable daily intake for sodium and calcium cyclamate, expressed as cyclamic acid, at up to 11 mg/kg body-weight.(11) In Europe, a temporary acceptable daily intake for sodium and calcium cyclamate, expressed as cyclamic acid, has been set at up to 1.5 mg/kg body-weight. LD50 (mouse, IP): 1.15 g/kg(12) LD50 (mouse, IV): 4.8 g/kg LD50 (mouse, oral): 17 g/kg LD50 (rat, IP): 1.35 g/kg LD50 (rat, IV): 3.5 g/kg LD50 (rat, oral): 15.25 g/kg
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection is recommended.
The use of cyclamates as artificial sweetners in food, soft drinks, and artificial sweetening tablets was at one time prohibited in the UK and some other countries owing to concern about the metabolite cyclohexylamine. However, this is no longer the case, and cyclamates are now permitted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral powder, solutions, chewable tablets, and suspensions). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Alitame; calcium cyclamate; cyclamic acid. Calcium cyclamate Empirical formula C12H24CaN2O6S22H2O Molecular weight 432.57 CAS number [5897-16-5] for the dihydrate; [139-06-0] for the anhydrous form. Synonyms Calcium N-cyclohexylsulfamate dihydrate; Cyclan; cyclohexanesulfamic acid calcium salt; cyclohexylsulfamic acid calcium salt; E952; Sucaryl calcium. Appearance White, odorless or almost odorless crystals or a crystalline powder with an intensely sweet taste. Acidity/alkalinity pH = 5.5–7.5 for a 10% w/v aqueous solution. Solubility Freely soluble in water; practically insoluble in benzene, chloroform, ethanol (95%), and ether. Cyclamic acid Empirical formula C6H13NO3S Molecular weight 179.23 CAS number [100-88-9] Synonyms Cyclamate; cyclohexanesulfamic acid; N-cyclohexylsulfamic acid; E952; hexamic acid; Sucaryl. Appearance White, odorless or almost odorless crystals or a crystalline powder with an intensely sweet taste. Melting point 169–1708C Solubility Slightly soluble in water.
The perceived intensity of sweeteners relative to sucrose depends upon their concentration, temperature of tasting, and pH, and on the flavor and texture of the product concerned. Intense sweetening agents will not replace the bulk, textural, or preservative characteristics of sucrose if sucrose is removed from a formulation. Synergistic effects for combinations of sweeteners have been reported, e.g. sodium cyclamate with saccharin sodium or acesulfame potassium. Sodium cyclamate has also been used to increase the solubility of neohesperidin dihydrochalcone in sweetener blends.(13) The PubChem Compound ID (CID) for sodium cyclamate is 23665706.