Tice Raymond R, Bassan Arianna, Amberg Alexander, Anger Lennart T, Beal Marc A, Bellion Phillip, Benigni Romualdo, Birmingham Jeffrey, Brigo Alessandro, Bringezu Frank, Ceriani Lidia, Crooks Ian, Cross Kevin, Elespuru Rosalie, Faulkner David M, Fortin Marie C, Fowler Paul, Frericks Markus, Gerets Helga H J, Jahnke Gloria D, Jones David R, Kruhlak Naomi L, Lo Piparo Elena, Lopez-Belmonte Juan, Luniwal Amarjit, Luu Alice, Madia Federica, Manganelli Serena, Manickam Balasubramanian, Mestres Jordi, Mihalchik-Burhans Amy L, Neilson Louise, Pandiri Arun, Pavan Manuela, Rider Cynthia V, Rooney John P, Trejo-Martin Alejandra, Watanabe-Sailor Karen H, White Angela T, Woolley David, Myatt Glenn J
RTice Consulting, Hillsborough, North Carolina, 27278, USA.
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Comput Toxicol. 2021 Nov;20. doi: 10.1016/j.comtox.2021.100191. Epub 2021 Sep 23.
Historically, identifying carcinogens has relied primarily on tumor studies in rodents, which require enormous resources in both money and time. models have been developed for predicting rodent carcinogens but have not yet found general regulatory acceptance, in part due to the lack of a generally accepted protocol for performing such an assessment as well as limitations in predictive performance and scope. There remains a need for additional, improved carcinogenicity models, especially ones that are more human-relevant, for use in research and regulatory decision-making. As part of an international effort to develop toxicological protocols, a consortium of toxicologists, computational scientists, and regulatory scientists across several industries and governmental agencies evaluated the extent to which models exist for each of the recently defined 10 key characteristics (KCs) of carcinogens. This position paper summarizes the current status of tools for the assessment of each KC and identifies the data gaps that need to be addressed before a comprehensive carcinogenicity protocol can be developed for regulatory use.
从历史上看，识别致癌物主要依赖于啮齿动物的肿瘤研究，这在资金和时间方面都需要巨大的资源。已经开发了用于预测啮齿动物致癌物的模型，但尚未得到监管机构的普遍认可，部分原因是缺乏进行此类评估的普遍接受的方案，以及预测性能和范围的局限性。仍然需要额外的、改进的致癌性模型，特别是那些与人类更相关的模型，用于研究和监管决策。作为制定毒理学方案的国际努力的一部分，来自多个行业和政府机构的毒理学家、计算科学家和监管科学家组成的联盟评估了针对最近定义的致癌物的10个关键特征（KC）中每个特征的模型存在程度。本立场文件总结了评估每个KC的工具的现状，并确定了在开发用于监管用途的全面致癌性方案之前需要解决的数据差距。
