Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria

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Autor(es): Haighton L, Roberts A, Walters B and Lynch B
Nome da Publicação : Regulatory Toxicology and Pharmacology, 2018 Jan 12; doi:
Ano de publicação : 2018


The current review assessed cancer studies of aspartame based on a quality appraisal using the Klimisch grading system. Nine studies having complete histopathology were included: three 2-year studies by Searle; three transgenic mice studies by the NTP; three lifetime studies by the Ramazzini Institute. A tenth study limited to brain tumors was not rated. None were determined as Klimisch Code 1 (reliable without restrictions). The Searle studies predated GLP standards but their methodology was comparable; transgenic mouse models are not validated, but are accepted as supporting data. These studies were rated Klimisch Code 2 (reliable with restrictions). The Ramazzini Institute used a lifetime model of their own design that has been questioned due to high rates of spontaneous tumors, issues with tumor type diagnosis and concerns about the impact of chronic infections. As many of these problems could be attributed to using animals that died or were terminated near end of life, along with the other problems noted, these studies were rated Klimisch Code 3 (not reliable). As the Klimisch Code 2 studies demonstrated a lack of carcinogenic potential, and as aspartame is hydrolyzed to common components and lacks genotoxic activity, a conclusion that aspartame is not carcinogenic is supported.


This systematic review by Haighton et al evaluated aspartame cancer bioassay methods using quality criteria (evaluation against the Klimisch grading system) and concluded that studies with highest rating support that aspartame is not carcinogenic in rodents.

The evaluation of the nine identified studies that were included in this systematic review demonstrates a lack of carcinogenic potential. This outcome, together with a lack of genotoxic activity and the fact that aspartame is hydrolysed in the gut to aspartic acid, phenylalanine and small amount of methanol, which are metabolized via normal well-characterized endogenous metabolic pathways, leads to the conclusion that aspartame is not carcinogenic.

The safety of aspartame has been confirmed by regulatory authorities globally. In Europe, the European Food Safety Authority (EFSA) scientific opinion on the re-evaluation of aspartame (E 951) as a food additive, one of the most comprehensive risk assessments of aspartame ever undertaken which was published in December 2013, concluded that aspartame is not a safety concern (EFSA, 2013). For more information about EFSA scientific opinion on the re-evaluation of aspartame (E 951) as a food additive, please click here.

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