Lack of potential carcinogenicity for acesulfame potassium - Systematic evaluation and integration of mechanistic data into the totality of the evidence
Lack of potential carcinogenicity for acesulfame potassium - Systematic evaluation and integration of mechanistic data into the totality of the evidence
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DOI：
10.1016/j.fct.2020.111375
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发表时间：
2020-07-01
影响因子：
4.3
通讯作者：
Borghoff, S. J.
中科院分区：
文献类型：
--
作者：
Chappell, G. A.;Wikoff, D. S.;Borghoff, S. J.
低热量和无热量甜味剂的安全性仍然是普遍关注的话题。大量证据表明无热量甜味剂安赛蜜钾 (Ace K) 不具有致癌性。本次评估的目的是使用一个框架对现有的机制数据进行系统评估，该框架将拟议的致癌物（KCC）关键特征定量整合到证据的整体中。对来自各种体外和体内测定的 800 多个 KCC 相关终点进行了质量、相关性和活性评估，并将其整合以确定 Ace K 通过 KCC 发挥作用的证据的整体强度。总体而言，识别数据的 KCC 缺乏活动（总体综合评分 < 0，并且没有活动证据的“强”分类）。再加上啮齿动物生物测定中不存在与治疗相关的肿瘤效应，这些结果支持了 Ace K 不太可能诱导致癌反应的结论。该评估采用了证据权重分析，包括考虑复杂异构数据集中的可靠性、模型系统的强度、活性和剂量等因素，以及癌症危害评估中多个数据流的最终整合。
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.