First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats

Abstract

The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation has conducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener. APM was administered with feed to 8-week-old Sprague-Dawley rats (100-150/sex/group), at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. The treatment lasted until natural death, at which time all deceased animals underwent complete necropsy. Histopathologic evaluation of all pathologic lesions and of all organs and tissues collected was routinely performed on each animal of all experimental groups. The results of the study show for the first time that APM, in our experimental conditions, causes a) an increased incidence of malignant-tumor-bearing animals with a positive significant trend in males (p < or = 0.05) and in females (p < or = 0.01), in particular those females treated at 50,000 ppm (p < or = 0.01); b) an increase in lymphomas and leukemias with a positive significant trend in both males (p < or = 0.05) and females (p < or = 0.01), in particular in females treated at doses of 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000 (p < or = 0.05), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.01); c) a statistically significant increased incidence, with a positive significant trend (p < or = 0.01), of transitional cell carcinomas of the renal pelvis and ureter and their precursors (dysplasias) in females treated at 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000 (p < or = 0.01), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.05); and d) an increased incidence of malignant schwannomas of peripheral nerves with a positive trend (p < or = 0.05) in males. The results of this mega-experiment indicate that APM is a multipotential carcinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the current acceptable daily intake. On the basis of these results, a reevaluation of the present guidelines on the use and consumption of APM is urgent and cannot be delayed.

Figure 1

. Comparison of untreated and treated male and female rats. (A) Mean daily feed consumption in males. (B) Mean daily feed consumption in females. (C) Mean body weights in males (M) and females (F). (D) Survival in males. (E) Survival in females. The arrow indicates the start of the experiment at 8 weeks of age.

Figure 2

(A) Carcinoma of the renal pelvis in a female rat administered 100,000 ppm APM in feed; H&E; magnification, 25×; bar = 500 μm. (B) Detail of the carcinoma shown in (A); H&E; magnification, 400×; bar = 20 μm. (C) Malignant schwannoma of cranial nerves resembling Antoni B type pattern in a male rat administered 100,000 ppm APM in feed; H&E; magnification, 200×; bar = 50 μm. (D) Immunohistochemical characterization with S100 protein of the schwannoma shown in (C); magnification, 1,000×; bar = 10 μm.