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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

CYCLAMATES
(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 73 (1999) (p. 195)

Cyclamic acid
CAS No.: 100-88-9
Chem. Abstr. Name: Cyclohexylsulfamic acid

Sodium cyclamate
CAS No.: 139-05-9
Chem. Abstr. Name: Cyclohexylsulfamic acid, monosodium salt

Calcium cyclamate
CAS No.: 139-06-0
Chem. Abstr. Name: Cyclohexylsulfamic acid, calcium salt (2:1)

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Cyclamates are widely used as non-caloric sweeteners, the average daily dietary intake generally being less than 3 mg/kg bw.

5.2 Human carcinogenicity data

Use of cyclamates was analysed separately in only four of the studies summarized in the monograph on saccharin and its salts. No increase in the risk for urinary bladder cancer was seen.

5.3 Animal carcinogenicity data

Sodium cyclamate was tested by oral administration in two experiments in mice, one of which was a multigeneration study, and in three experiments in rats. No treatment-related increase in tumour incidence was found. Sodium cyclamate was also tested by oral administration in other experiments in mice, rats, hamsters and monkeys, but these experiments could not be evaluated because of various inadequacies or incomplete reporting.

Pellets containing sodium cyclamate induced bladder tumours in mice after implantation into the bladder; however, the protocol was considered to be inadequate for determining carcinogenicity.

Calcium cyclamate was tested by oral administration in a two-generation experiment in rats; no difference in tumour incidence was seen between treated and control animals.

In two studies in rats, sodium cyclamate was administered orally after a known carcinogen. The incidence of urinary bladder tumours was increased in one study, whereas only slight enhancement was found in a second study.

5.4 Other relevant data

Cyclamates are incompletely absorbed from the gastrointestinal tract of humans and other mammals. Most is excreted in the urine unchanged. Cyclamates are partially converted by gastrointestinal microflora to cyclohexylamine, which is absorbed. Cyclamates and cyclohexylamine can produce testicular toxicity in rats.

Cyclamates have not been observed to produce developmental toxicity in mice, rats, rabbits, hamsters, dogs or rhesus monkeys. Negative results were obtained in a number of short-term assays for teratogenicity in vitro and in vivo. Cyclamates were not teratogenic in mice, rats or rhesus monkeys, but there were some indications of reduced growth and viability of embryos in some studies. Rat embryos exposed in vitro showed altered morphological development in one study.

Cyclamates did not produce chromosomal aberrations in peripheral lymphocytes of volunteers. Cyclamates were not genotoxic in rodents in vivo but were genotoxic in mammalian cells in vitro.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of cyclamates.

There is inadequate evidence in experimental animals for the carcinogenicity of cyclamates.

Overall evaluation

Cyclamates are not classifiable as to their carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluations: Vol. 22 (1980); Suppl. 7 (1987)

Synonyms

Cyclamic acid

Sodium cyclamate

Calcium cyclamate


Last updated: 30 September 1999





















    See Also:
       Toxicological Abbreviations
       Cyclamates  (IARC Summary & Evaluation, Supplement7, 1987)
       Cyclamates  (IARC Summary & Evaluation, Volume 22, 1980)