Cohen Samuel M, Klaunig James, Meek M Elizabeth, Hill Richard N, Pastoor Timothy, Lehman-McKeeman Lois, Bucher John, Longfellow David G, Seed Jennifer, Dellarco Vicki, Fenner-Crisp Penelope, Patton Dorothy
ILSI RSI Steering Committee, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA.
Toxicol Sci. 2004 Apr;78(2):181-6. doi: 10.1093/toxsci/kfh073. Epub 2004 Jan 21.
Defining the mode(s) of action by which chemicals induce tumors in laboratory animals has become a key to judgments about the relevance of such tumor data for human risk assessment. Frameworks for analyzing mode of action information appear in recent U.S. EPA and IPCS publications relating to cancer risk assessment. This FORUM paper emphasizes that mode of action analytical frameworks depend on both qualitative and quantitative evaluations of relevant data and information: (1) presenting key events in the animal mode of action, (2) developing a "concordance" table for side-by-side comparison of key events as defined in animal studies with comparable information from human systems, and (3) using data and information from mode of action analyses, as well as information on relative sensitivity and exposure, to make weight-of-evidence judgments about the relevance of animal tumors for human cancer assessments. The paper features a systematic analysis for using mode of action information from animal and human studies, based in part on case examples involving environmental chemicals and pharmaceuticals.
确定化学物质在实验动物体内诱发肿瘤的作用方式，已成为判断此类肿瘤数据与人类风险评估相关性的关键。近期美国环境保护局（EPA）和国际化学品安全规划署（IPCS）发布的有关癌症风险评估的出版物中出现了分析作用方式信息的框架。本论坛论文强调，作用方式分析框架依赖于对相关数据和信息的定性和定量评估：（1）呈现动物作用方式中的关键事件；（2）编制一个“一致性”表格，用于将动物研究中定义的关键事件与人类系统中的可比信息进行并列比较；（3）利用作用方式分析的数据和信息，以及相对敏感性和暴露信息，对动物肿瘤与人类癌症评估的相关性进行证据权重判断。本文以动物和人类研究中的作用方式信息的系统分析为特色，部分基于涉及环境化学品和药物的案例。
