Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates

S. Takayama, A. G. Renwick, S. L. Johansson, U. P. Thorgeirsson, M. Tsutsumi, D. W. Dalgard, S. M. Sieber

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Abstract

Twenty-one monkeys (cynomolgus, rhesus, African green) were fed cyclamate (100 mg/kg and 500 mg/kg) in the diet five times per week from a few days after birth and continuing for up to 24 years. Malignant tumors were diagnosed in three 24-year-old cyclamate monkeys; these were metastatic colon carcinoma (rhesus; 500 mg/kg), metastatic hepatocellular carcinoma (cynomolgus; 500 mg/kg), and a small, well differentiated adenocarcinoma of the prostate (cynomolgus; 100 mg/kg). Benign tumors were found at necropsy in three females; these were adenoma of the thyroid gland (rhesus; 100 mg/kg) and two cases of leiomyoma of the uterus (rhesus; 100 mg/kg and 500 mg/kg). No tumors were detected in an age-matched control group of 16 monkeys. Examination of the testes revealed complete testicular atrophy in one of the old cyclamate monkeys, and focal germ cell aplasia (Sertoli-only tubules) in two other cyclamate monkeys. Focal spermatogenic interruption (maturation arrest) at various germ cell levels mixed with normal spermatogenesis was observed in both the cyclamate-treated and the control monkeys, all of which were over 20 years old. Measurements of terminal cyclohexylamine concentrations showed that three of the males dosed with cyclamate at 500 mg/kg were high converters, with plasma concentrations comparable to the levels that produce testicular atrophy in rats. However, only one of the three high converters showed histologic evidence of irregular spermatogenesis. The overall conclusion is that the testicular abnormalities and the sporadic cases of different malignancies found after more than 20 years of dosing do not provide clear evidence of a toxic or carcinogenic effect of sodium cyclamate in monkeys.

Original languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalToxicological Sciences
Volume53
Issue number1
StatePublished - Jan 24 2000

Fingerprint

Cyclamates
Primates
Toxicity
Haplorhini
Tumors
Spermatogenesis
Germ Cells
Atrophy
Neoplasms
Cyclohexylamines
Cells
Macaca fascicularis
Poisons
Leiomyoma
Nutrition
Macaca mulatta
Adenoma
Uterus
Testis
Rats

Keywords

  • Carcinogen
  • Cyclamate
  • Malignancies
  • Primates
  • Spermatogenesis
  • Testicular abnormalities
  • Toxicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Takayama, S., Renwick, A. G., Johansson, S. L., Thorgeirsson, U. P., Tsutsumi, M., Dalgard, D. W., & Sieber, S. M. (2000). Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates. Toxicological Sciences, 53(1), 33-39.

Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates. / Takayama, S.; Renwick, A. G.; Johansson, S. L.; Thorgeirsson, U. P.; Tsutsumi, M.; Dalgard, D. W.; Sieber, S. M.

In: Toxicological Sciences, Vol. 53, No. 1, 24.01.2000, p. 33-39.

Research output: Contribution to journalArticle

Takayama, S, Renwick, AG, Johansson, SL, Thorgeirsson, UP, Tsutsumi, M, Dalgard, DW & Sieber, SM 2000, 'Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates', Toxicological Sciences, vol. 53, no. 1, pp. 33-39.
Takayama S, Renwick AG, Johansson SL, Thorgeirsson UP, Tsutsumi M, Dalgard DW et al. Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates. Toxicological Sciences. 2000 Jan 24;53(1):33-39.
Takayama, S. ; Renwick, A. G. ; Johansson, S. L. ; Thorgeirsson, U. P. ; Tsutsumi, M. ; Dalgard, D. W. ; Sieber, S. M. / Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates. In: Toxicological Sciences. 2000 ; Vol. 53, No. 1. pp. 33-39.
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