Lack of potential carcinogenicity for sucralose – Systematic evaluation and integration of mechanistic data into the totality of the evidence

Author(s): Chappell, G.A., Borghoff, S.J., Pham L, Doepker, C.L., Wikoff, D.S
Publication name: Food and Chemical Toxicology 2020; 135 : 110898. 10.1016/j.fct.2019.110898
Publication year: 2019


Sucralose is widely used as a sugar substitute. Many studies and authoritative reviews have concluded that sucralose is non-carcinogenic, based primarily on animal cancer bioassays and genotoxicity data. To add to the body of knowledge on the potential carcinogenicity of sucralose, a systematic assessment of mechanistic data was conducted. This entailed using a framework developed for the quantitative integration of data related to the proposed key characteristics of carcinogens (KCCs). Data from peer-reviewed literature and the ToxCast/Tox21 database were evaluated using an algorithm that weights data for quality and relevance. The resulting integration demonstrated an overall lack of activity for sucralose across the KCCs, with no “strong” activity observed for any KCC. Almost all data collected demonstrated inactivity, including those conducted in human models. The overall lack of activity in mechanistic data is consistent with findings from animal cancer bioassays. The few instances of activity across the KCC were generally accompanied by limitations in study design in the context of either quality and/or dose and model relevance, highlighted upon integration of the totality of the evidence. The findings from this comprehensive and integrative evaluation of mechanistic data support prior conclusions that sucralose is unlikely to be carcinogenic in humans.


The outcomes of this comprehensive and integrative evaluation of mechanistic data support prior conclusions from food safety agencies worldwide that sucralose is not carcinogenic.

The results of this systematic and structured assessment of mechanistic data, using categorization and evaluation according to key characteristics of carcinogens (KCCs), complement other assessments from authoritative bodies in concluding that sucralose is safe for its intended use and without concern for mutagenicity and carcinogenicity. These findings are also in agreement with recent comprehensive reviews, which have similarly reported that sucralose is not carcinogenic (Berry et al., 2016Magnuson et al., 2017).

The current review adds further evidence with inclusion and evaluation of mechanistic data, i.e., data that could indicate a mechanism by which a substance might cause or promote cancer incidence. Further, the incorporation of mechanistic data can be particularly helpful in the absence of human epidemiological studies, and can serve as a component in a weight-of-evidence assessment regarding the potential for carcinogenicity. A key strength of this assessment is the incorporation of mechanistic data from various sources (i.e., databases that include HTS data, peer-reviewed literature), different study designs, and a wide array of endpoints ranging from molecular events to apical tissue-level responses.

The overall lack of activity for sucralose as tested in various models and across mechanistic endpoints organized by KCCs, coupled with the lack of carcinogenicity in standard two-year cancer bioassays in rodents, reinforces regulatory conclusions that sucralose does not present carcinogenic hazard to humans.

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