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.