Toxic Response of Rats to Cyclamates in Chow and Semisynthetic Diets

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Abstract
Cyclamates were fed to rats in 2 independently conducted studies. In study one, sodium and calcium cyclamate in commercial chow diets were fed, at dietary levels from 0.4–10%, to male and female weanling Osborne-Mendel rats for 101 weeks; in study two, 1 and 2% calcium cyclamate in semisynthetic diets containing 10 and 20% casein were fed to male weanling Holtzman rats for 75 weeks. In both studies, adverse reactions were noted. With the semisynthetic diet, growth rate was depressed, soft stools were produced, and the rate of kidney and urinary bladder lesions was increased. These adverse reactions did not appear to be affected by the protein content of the diet. No observed cytogenetic damage was produced by calcium cyclamate ingestion. With the chow diet, survival decreased and urinary bladder and kidney lesions increased; this increase was much more marked in severity and incidence than that with the semi-synthetic diets. The lesions noted with the highest frequency in the kidneys were nephrocalcinosis and calyceal polyposis, and in the urinary bladder, epithelial hyperplasia, thickening or edema of the urinary bladder wall, and mucosal papilloma. Transitional cell carcinoma with varying degrees of invasion was detected in the urinary bladders of 3 of the 23 rats receiving calcium cyclamate in the chow diets. Two of these carcinomas were in rats fed diets containing only 0.4% of this compound. Bladder calculi were also occasionally present and were in 2 of the bladders with carcinomas. These lesions were not seen in any rats fed control diets.

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