Following a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the results of a long-term carcinogenicity study with prenatal exposure to the artificial sweetener aspartame, performed by The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (ERF) and published in June 2007 by Soffritti et al.. The authors concluded that the results of their study not only confirm, but also reinforce their first experimental demonstration (published in 2005 and 2006) of aspartame’s multipotential carcinogenicity at a dose level close to the human Acceptable Daily Intake (ADI). Based on the results of this study, the authors further postulated that when lifespan exposure to aspartame begins during fetal life, its carcinogenic effects are increased.
During the 1980s, aspartame has been authorised for use in foods and as a table-top sweetener by several Member States, and European legislation harmonising its use in foodstuffs was introduced in 1994 following thorough safety evaluations by the Scientific Committee on Food (SCF) in 1984 and 1988. Further reviews of aspartame data were carried out by the SCF in 1997 and 2002. In 2006, the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) assessed a long-term carcinogenicity study on aspartame performed by the ERF and published by Soffritti et al. in 2005 and 2006. Based on all the evidence available from the ERF study and other recent studies and previous evaluations, the AFC Panel concluded that there was no reason to revise the previously established ADI for aspartame of 40 mg/kg bw (EFSA, 2006).
In the second ERF study on aspartame in rats, published in 2007, dietary concentrations of 400 and 2000 mg aspartame/kg diet equivalent to doses of 20 and 100 mg aspartame/kg bw/day were used. The rats were exposed to aspartame from the 12th day of gestation until natural death. The group size was 95/sex in the control and 70/sex in the low- and high-dose groups. The authors reported a significant dose-related increase of malignant tumour-bearing males, particularly in the high-dose group (p<0.01, Cox regression model), a significant increase in incidence of lymphomas/leukaemias in males from the high-dose group (p<0.05), a significant dose-related increase in incidence of lymphomas/leukaemias in females (p<0.01), particularly in the high-dose group (p<0.01), and a significant dose-related increase in incidence of mammary carcinomas in females (p<0.05), particularly in the high-dose group (p<0.05).
The Panel’s assessment of the ERF carcinogenicity study with prenatal exposure on aspartame as reported by Soffritti et al. was directed towards establishing the relevance of the reported findings to human health. In carrying out its assessment the main information available to the Panel was the published paper, in which the presentation of pathological findings was restricted to the incidence of malignant tumours, total number of malignant tumours per group, incidence of lymphomas/leukaemias, and incidence of mammary carcinomas. Further data from this study were requested by EFSA in April 2007, January 2008 and July 2008 in order to aid the interpretation of the study. On 19 February 2009, the Ramazzini Institute submitted to EFSA some of the requested data.
The Panel concluded that:
- Evaluation of aggregated malignant tumour incidences as evidence of carcinogenic potential of the test compound can only be performed based on a thorough consideration of all tumour data including onset, and data on non-neoplastic, hyperplastic and preneoplastic lesions but these data were not provided by the authors. Limited information on the presence of inflammatory changes in the lungs of animals with lymphomas and leukemias were provided by the ERF in the additional submission.
- The majority of the lymphomas and leukemias observed appeared to have developed in rats suffering from inflammatory changes in the lungs, which is characteristic for chronic respiratory disease. In accordance with the previous view of the AFC Panel, these changes were not considered to be related to the treatment with aspartame.
- The increase in incidence of mammary carcinoma is not considered indicative of a carcinogenic potential of aspartame since the incidence of mammary tumours in female rats is rather high and varies considerably between carcinogenicity studies. The Panel also noted that an increased incidence of mammary carcinomas was not reported in the previous ERF study with aspartame which used much higher doses of the compound
Overall, the Panel concluded, on the basis of all the evidence currently available including the last published ERF study that there is no indication of any genotoxic or carcinogenic potential of aspartame and that there is no reason to revise the previously established ADI for aspartame of 40 mg/kg bw/day.