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Environmental Health Perspectives (EHP) is a monthly journal of peer-reviewed research and news on the impact of the environment on human health. EHP is published by the National Institute of Environmental Health Sciences and its content is free online. Print issues are available by paid subscription.DISCLAIMER
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Environmental Health Perspectives Volume 114, Number 3, March 2006 Open Access
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First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Luca Lambertini, Eva Tibaldi, and Anna Rigano

Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Bologna, Italy

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 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. Key words: , , , , , , . Environ Health Perspect 114:379-385 (2006) . doi:10.1289/ehp.8711 available via http://dx.doi.org/ [Online 17 November 2005]


Address correspondence to M. Soffritti, Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Castello di Bentivoglio, Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. Telephone: 39-051-6640460. Fax: 39-051-6640223. E-mail: crcfr@ramazzini.it

We thank the U.S. National Toxicology Program for convening a group of pathologists at the National Institute of Environmental Health Sciences to provide a second opinion for a set of malignant lesions and their precursors related to aspartame treatment, and for their help in statistical analysis. We also thank all of the staff involved in the project.

This research was supported by the European Ramazzini Foundation of Oncology and Environmental Sciences.

The authors declare they have no competing financial interests.

Received 3 October 2005 ; accepted 16 November 2005.

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