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

• Published in: Food and chemical toxicology Vol. 141; p. 111375
• Main Authors: Chappell, G.A., Wikoff, D.S., Doepker, C.L., Borghoff, S.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2020
• Subjects: Ace K; Acesulfame potassium; Animals; Carcinogenicity; Carcinogenicity Tests; High-Throughput Screening Assays; Humans; Key characteristic of carcinogens; Mechanisms; Sweetener; Sweetening Agents - toxicity; Thiazines - toxicity; Mechanisms; Sweetener; Ace K; Carcinogenicity; Acesulfame potassium; Key characteristic of carcinogens
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111375

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. •Identified, appraised, and integrated mechanistic data to assess potential carcinogenicity of acesulfame potassium (Ace K).•Includes over 800 endpoints collected from literature and high-throughput screening data.•Mechanistic data were evaluated for potential activity related to one or more key characteristics of carcinogens (KCC).•Overall, there was a lack of activity for Ace K per KCC, supporting the lack of Ace K carcinogenicity in animal studies.