Research Notes: Food Safety

Environ Health Perspect. 2007 Jun.
Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal Life Increases Cancer Effects in Rats.
Morando Soffritti, Fiorella Belpoggi, Eva Tibaldi, Davide Degli Esposti, Michela Lauriola.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Bologna, Italy.
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Background. In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM), administered with feed at various doses to 8 week-old Sprague Dawley rats for the lifespan, is a multipotent carcinogenic agent. Objective. The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods. The study was conducted on groups of 70-95 male and female Sprague Dawley rats, administered APM with feed at concentrations of 2000, 400, or 0 ppm from the 12th day of fetal life until natural death. Results. The results of the study show: a) a significant dose-related increase of malignant tumor-bearing animals in males (p<0.01), in particular in the group treated at 2000 ppm (p<0.01); b) a significant increase of the incidence in lymphomas/leukemias in males treated at 2000 ppm (p<0.05) and a significant dose-related increase of the incidence of lymphomas/leukemias in females (p<0.01), in particular in the group treated at 2000 ppm (p<0.01); c) a significant dose-related increase of the incidence of mammary cancer in females (p<0.05), in particular in the group treated at 2000 ppm (p<0.05). Conclusions. The results of this carcinogenicity bioassay not only confirm, but also reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake (ADI) for humans. Furthermore, the study demonstrates that when lifespan exposure to APM begins during fetal life, its carcinogenic effects are increased.

Ann N Y Acad Sci. 2006 Sep.
Results of long-term carcinogenicity bioassay on Sprague-Dawley rats exposed to aspartame administered in feed.
Belpoggi F, Soffritti M, Padovani M, Degli Esposti D, Lauriola M, Minardi F.
Cesare Maltoni Cancer Research Center, European Foundation of Oncology and Environmental Sciences B. Ramazzini, 40010 Bentivoglio, Bologna, Italy.

Aspartame (APM) is one of the most widely used artificial sweeteners in the world. Its ever-growing use in more than 6000 products, such as soft drinks, chewing gum, candy, desserts, etc., has been accompanied by rising consumer concerns regarding its safety, in particular its potential long-term carcinogenic effects. In light of the inadequacy of the carcinogenicity bioassays performed in the 1970s and 1980s, a long-term mega-experiment on APM was undertaken at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation on groups of male and female Sprague-Dawley rats (100-150/sex/group), 8 weeks old at the start of the experiment. APM was administered in feed at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. Treatment lasted until spontaneous death of the animals. The results of the study demonstrate that APM causes: (a) an increased incidence of malignant tumor-bearing animals, with a positive significant trend in both sexes, and in particular in females treated at 50,000 ppm (P < or = 0.01) when compared to controls; (b) an increase in lymphomas-leukemias, with a positive significant trend in both sexes, and 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), 2000 (P < or = 0.05), and 400 ppm (P < or = 0.01); (c) a statistically significant increased incidence, with a positive significant trend, of transitional cell carcinomas of the renal pelvis and ureter in females and particularly in those treated at 100,000 ppm (P < or = 0.05); and (d) an increased incidence of malignant schwannomas of the peripheral nerves, with a positive trend in males (P < or = 0.05). The results of this mega-experiment indicate that APM, in the tested experimental conditions, is a multipotential carcinogenic agent.

Environ Health Perspect. 2006 Mar.
First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats.
Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Bologna, Italy.
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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.