Bladder Tumors in Rats Fed Cyclohexylamine or High Doses of a Mixture of Cyclamate and Saccharin

@article{Price1970BladderTI,
  title={Bladder Tumors in Rats Fed Cyclohexylamine or High Doses of a Mixture of Cyclamate and Saccharin},
  author={J. M. Price and Claude G. Biava and Bernard L. Oser and Eugene E. Vogin and J Steinfeld and Herbert L. Ley},
  journal={Science},
  year={1970},
  volume={167},
  pages={1131 - 1132}
}
Papillary transitional cell tumors were found in the urinary bladders in 8 rats out of 80 that received 2600 milligrams per kilogram of body weight per day of a mixture of sodium cyclamate and sodium saccharin (10:1) for up to 105 weeks. From week 79 on, several of these rats received cyclohexylamine hydrochloride (125 milligrams per kilogram per day, the molecular equivalent of the conversion of about 10 percent of the cyclamate dosage to cyclohexylamine) in addition to the sodium cyclamate… 
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Neomycin, polymyxin, or gentamicin added to faeces incubations inhibited or blocked cyclohexylamine formation at low doses, suggesting that the micro-organism(s) responsible for the conversion may belong to aerobic, gram-negative species.
Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis.
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Saccharin was considerably more potent as a promoting agent than was tryptophan, inducing higher incidences of bladder tumors and having a shorter latent period than was saccharin, who might act as tumor-promoting agents during bladder carcinogenesis.
Production of Urinary Bladder Carcinomas in Mice by Sodium Saccharin
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Pellets weighing 20 to 24 milligrams and containing 20 percent sodium saccharin suspended in cholesterol were surgically implanted into the urinary bladder lumens of female Swiss mice under ether anesthesia, and the exposure of the mouse bladder to saccharine was very brief.
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References

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Conversion of Cyclamate to Cyclohexylamine in Rats
TLDR
The urine of five male laboratory workers for 5 days after each had been given a single dose of 3 g sodium cyclamate was analysed and one of the five subjects was found to excrete 0.8 per cent of the dose of cyclamate which was administered as cyclohexylamine; most of thedose was excreted as free cyclamate.
A comparison of the chronic toxicities of synthetic sweetening agents.
TLDR
The results indicate that the synthetic sweetening agents, saccharin, sodium cyclohexyl sulfamate, dulcin, and P-4000 may be divided into a toxic group and a relatively nontoxic group.