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1513500 
Journal Article 
First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats 
Soffritti, M; Belpoggi, F; Esposti, DD; Lambertini, L; Tibaldi, E; Rigano, A 
2005 
Yes 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
114 
379-385 
English 
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 A 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 <=
0.05) and in females (p <= 0.01), in particular those females treated at 50,000 ppm (p <= 0.01);
b) an increase in lymphomas and leukemias with a positive significant trend in both males (p <=
0.05) and females (p <= 0.01), in particular in females treated at doses of 100,000 (p <= 0.01),
50,000 (p <= 0.01), 10,000 (p <= 0.05), 2,000 (p <= 0.05), or 400 ppm (p <= 0.01); c) a
statistically significant increased incidence, with a positive significant trend (p <= 0.01), of
transitional cell carcinomas of the renal pelvis and ureter and their precursors (dysplasias) in
females treated at 100,000 (p <= 0.01), 50,000 (p <= 0.01), 10,000 (p <= 0.01), 2,000 (p <=
0.05), or 400 ppm (p <= 0.05); and d) 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 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. 
artificial sweetener; aspartame; carcinogenicity; lymphomas; malignant schwannomas; rats; renal pelvis carcinomas 
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