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

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Author(s): Chappell GA, Wikoff DS, Doepker CL, Borghoff SJ
Publication name: Food Chem Toxicol. 2020 Apr 28:111375. doi: 10.1016/j.fct.2020.111375. [Epub ahead of print]
Publication year: 2020


The safety of low- and no-calorie sweeteners remains a topic of general interest. Substantial evidence exists demonstrating a lack of carcinogenicity of the no-calorie sweetener acesulfame potassium (Ace K). The objective of this evaluation was to conduct a systematic assessment of available mechanistic data using a framework that quantitatively integrates proposed key characteristics of carcinogens (KCCs) into the totality of the evidence. Over 800 KCC-relevant endpoints from a variety of in vitro and in vivo assays were assessed for quality, relevance, and activity, and integrated to determine the overall strength of the evidence for plausibility that Ace K acts through the KCC. Overall, there was a lack of activity across the KCCs (overall integrated score <0 and no “strong” categorization for evidence of activity) in which data were identified. Together with the absence of treatment-related tumor effects in rodent bioassays, these results support the conclusion that Ace K is unlikely to induce a carcinogenic response. This assessment employed a weight of the evidence analysis that includes the consideration of factors such as reliability, strength of the model system, activity, and dose in a complex and heterogeneous dataset, and the ultimate integration of multiple data streams in the cancer hazard evaluation.


The present structured and integrative assessment of mechanistic data supports the lack of carcinogenic potential from exposure to acesulfame potassium (Ace K). The outcomes of this study are consistent with conclusions from regulatory food safety authorities worldwide supporting that Ace K is safe and non-carcinogenic. The current work adds further evidence with inclusion and evaluation of all available evidence streams (human, animal), and mechanistic data, i.e., data that could indicate a mechanism by which a substance might cause or promote cancer incidence.

This study by Chappell et al aimed to identify, evaluate and integrate mechanistic data to assess potential carcinogenicity of Ace K using a structured, quantitative framework. These mechanistic data were evaluated for potential activity related to one or more key characteristics of carcinogens (KCC). 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. Over 800 endpoints collected from literature and high-throughput screening data from a variety of in vitro and in vivo assays were included in this study.

The findings of this assessment of KCC-relevant mechanistic data demonstrated that Ace K exposures are unlikely to pose a carcinogenic risk to humans, which is in agreement with previously published evaluations of this sweetener by regulatory bodies around the world.

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