Cohen Samuel M, Meek M E Bette, Klaunig James E, Patton Dorothy E, Fenner-Crisp Penelope A
University of Nebraska Medical Center, Omaha, NE, USA.
Crit Rev Toxicol. 2003;33(6):581-9. doi: 10.1080/713608371.
Risk assessment policies and practice place increasing reliance on mode of action (MOA) data to inform conclusions about the human relevance of animal tumors. In June 2001, the Risk Science Institute of the International Life Sciences Institute formed a workgroup to study this issue. The workgroup divided into two subgroups, one developing and testing a "framework" for MOA relevance analysis and the other conducting an in-depth analysis of peroxisome proliferation-activated receptor (PPAR)alpha activation as the MOA for some animal carcinogens. This special issue of Critical Reviews in Toxicology presents the scientific reports emerging from this activity. These reports serve several purposes. For risk assessors in and out of government, they offer a new human relevance framework (HRF) that complements and extends existing guidance from other organizations. Regarding the specific MOA for peroxisome proliferating chemicals, these reports offer a state-of-the-science review of this important MOA and its role in tumorigenesis in three different tissues (liver, testis, and pancreas). The case studies in these reports present models for using MOA information to evaluate the hazard potential for humans. The cases also illustrate the substantial impact of a complete human relevance analysis, as distinct from an animal MOA analysis alone, on the nature and scope of risk assessment.
风险评估政策与实践越来越依赖作用模式（MOA）数据，以便就动物肿瘤与人类的相关性得出结论。2001年6月，国际生命科学研究所风险科学研究所成立了一个工作组来研究这个问题。该工作组分为两个小组，一个小组制定并测试MOA相关性分析的“框架”，另一个小组对过氧化物酶体增殖激活受体（PPAR）α激活作为某些动物致癌物的作用模式进行深入分析。《毒理学评论》的这一特刊展示了这项活动产生的科学报告。这些报告有几个目的。对于政府内外的风险评估人员来说，它们提供了一个新的人类相关性框架（HRF），补充并扩展了其他组织现有的指南。关于过氧化物酶体增殖化学物质的具体作用模式，这些报告对这一重要作用模式及其在三种不同组织（肝脏、睾丸和胰腺）肿瘤发生中的作用进行了科学现状综述。这些报告中的案例研究提供了利用作用模式信息评估人类潜在危害的模型。这些案例还说明了完整的人类相关性分析，与仅进行动物作用模式分析不同，对风险评估的性质和范围产生的重大影响。
