Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to a new long‐term carcinogenicity study on aspartame

Abstract

Aspartame has undergone extensive testing in animals and studies in humans, including four animal carcinogenicity studies conducted during the 1970s and early 1980s. These studies, together with studies on genotoxicity, were evaluated by regulatory bodies worldwide and it was concluded that they did not show evidence of genotoxic or carcinogenic potential for aspartame. Since its approval, however, the safety of aspartame has been repeatedly questioned, with discussions focusing not only on the safety of aspartame itself, but also on the safety of its breakdown products, aspartic acid, phenylalanine and methanol. All these substances occur naturally in the body. In response to such questions, the SCF undertook a further review of all the data on aspartame in 2002 and concluded that there was no need to revise the outcome of their earlier risk assessment or the previously established Acceptable Daily Intake (ADI) for aspartame, of 40 mg/kg body weight (bw).The AFC Panel has assessed the new carcinogenicity study, using not only the ERF publications but also a more extensive report provided to EFSA by the ERF at the end of 2005 and further data from the same study provided by ERF in April 2006. The Panel noted that this lifetime study, using more dose groups and more animals per group than conventional carcinogenicity studies, represented a substantial effort and had the potential to be more sensitive to low incidence effects. After its evaluation the Panel considers that the study has flaws which bring into question the validity of the findings, as interpreted by the ERF. In particular, the high background incidence of chronic inflammatory changes in the lungs and other vital organs and tissues and the uncertainty about the correctness of the diagnoses of some tumour types were major confounding factors in the interpretation of the findings of the study.The Panel's conclusions on the findings of the ERF study include the following:• The increased incidence of lymphomas/leukaemias reported in treated rats was unrelated to aspartame, given the high background incidence of chronic inflammatory changes in the lungs and the lack of a positive dose-response relationship. It is wellknown that such tumours can arise as a result of abundant lymphoid hyperplasia in the lungs of rats suffering from chronic respiratory disease. The most plausible explanation of the findings in this study with respect to lymphomas/leukaemias is that they have developed in a colony suffering from chronic respiratory disease. The slight increase in incidence of these tumours in rats fed aspartame is considered to be an incidental finding of the ERF study and can therefore be dismissed.• The preneoplastic and neoplastic lesions of the renal pelvis, ureter and bladder occurring primarily in female rats along with renal calcification were most probably treatment-related, at least at the higher doses. It is widely accepted that the effect is a high dose effect of irritant chemicals or chemicals producing renal pelvic calcification as a result of im...

Clinical presentation and treatment of lymphoma in companion rats (Rattus norvegicus; 2008–2020)

“…This raises the possibility of an environmental component to the development of lymphoma in these animals. 26 In addition, an interesting consideration would be whether the inflammation associated with chronic respiratory disease could be involved in the development of neoplasia. 27 Two of the rats in the present study were positive for M pulmonis.…”

Zebrafish Behavioral Phenomics Links Artificial Sweetener Aspartame to Behavioral Toxicity and Neurotransmitter Homeostasis

“…This conclusion was confirmed by the US FDA, which issued an opinion on April 20, 2007, that APM is not long-term carcinogenic and that it is safe for people to consume APM for a long time. The JECFA under the World Health Organization and the EFSA have evaluated its safety, and the experiments conducted on animals have projected that the daily intake of 2.4 g of APM for a normal healthy population weighing about 60 kg would not cause cancer. − However, recent research studies demonstrated new evidence to indicate that APM is a chemical carcinogen in rodents. Whether or not APM is safe needs further experimental determination in detail.…”

“…The existing animal experiments have indicated the potential health effect of APM. Recent studies have revealed that APMfed (25,50, and 100 mM) zebrafish hyperlipidemia model exhibited weight gain, hyperglycemia, and acute swimming defects. 20 APM (0.25 g/L) may affect glucose homeostasis and spatial cognition in male mice, 21 while other researchers reported that the no obvious adverse effect concentration (NOAEC) in rats and dogs is up to 4000 mg/kg body weight/ day.…”

Aspartame and cancer – new evidence for causation

“…At the heart of this debate were doubts raised about the accuracy of the RI's histopathological diagnoses -in particular the RI's diagnoses of pulmonary lymphomas and leukemiasin animals exposed to aspartame [14,16]. The European Food Safety Agency (EFSA) made the unsubstantiated claim that the RI's animal colony was poorly managed and that the experimental animals were subject to uncontrolled infections [8,9,17]. Schoeb et al speculated further that pulmonary lesions diagnosed as lymphomas and leukemias by RI might have been inflammatory lesions caused by Mycoplasma pulmonis infections [18].…”

“…National and international public health agencies need to take careful notice of these revalidated findings. Previous facile dismissals of the carcinogenicity of aspartame can no longer be sustained [8,9,17,18]. Long experience documents that delay in acting on welldocumented evidence of chemical carcinogenesis results in unnecessary disease and preventable death [26][27][28].…”