Acknowledgements: A special thanks to the US National Toxicology Program (NTP) for convening a group of pathologists at NIEHS in order to provide a second opinion for a set of lesions of malignancies and their precursors related to the APM treatment, and for the help in statistical analysis. A special thanks also to all the staff who were involved in the project. This research was entirely supported by European Ramazzini Foundation of Oncology and Environmental Sciences, Bologna, Italy. Authors do not havecompeting financial interests in relation to the submitted article.
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. Histopathological evaluation of all pathological 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: 1) an increased incidence of malignant tumor-bearing animals with a positive significant trend in males (p0.05) and in females (p0.01), in particular those females treated at 50,000 ppm (p0.01); 2) an increase in lymphomas and leukemias with a positive significant trend in both males (p0.05) and females (p0.01), in particular in females treated at doses of 100,000 (p0.01), 50,000 (p0.01), 10,000 (p0.05), 2,000 (p0.05), 400 (p0.01) ppm; 3) a statistically significant increased incidence, with a positive significant trend (p0.01) of transitional cell carcinomas of the renal pelvis and ureter and their precursors (dysplasias) in females treated at 100,000 (p0.01), 50,000 (p0.01), 10,000(p0.01), 2,000 (p0.05) and 400 ppm (p0.05); and 4) an increased incidence of malignant schwannomas of peripheral nerves with a positive trend (p 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 b.w., much less than the current acceptable daily intake (ADI). On the basis of these results, a re-evaluation of the present guidelines on the use and consumption of APM is urgent and cannot be delayed.