National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Toxicol Appl Pharmacol. 2013 Sep 15;271(3):299-308. doi: 10.1016/j.taap.2011.01.017. Epub 2011 Feb 2.
The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment.
迄今为止，毒理基因组学数据在风险评估中的主要作用是补充更传统的体外和体内毒理学数据。本文重点介绍了毒理基因组学数据在人类健康风险评估中（例如乙草胺和砷化合物）的现有评估实例，这些实例仅限于将毒理基因组学数据应用于作用机制的信息。本文回顾了监管政策背景，并强调了最终实现监管部门认可的重要努力。为风险评估目的而设计的一些特定化学物质的研究工作采用了机制或作用模式假设检验和生成策略。还讨论了利用毒理基因组学数据进行筛选、测试和风险评估的大规模努力所取得的进展。这些努力包括改进进行毒理基因组学研究的方法和分析由此产生的数据集。当前限制毒理基因组学在风险评估中定义作用模式或作用机制的应用的问题与相关的研究需求一起进行了讨论。总之，随着化学风险评估从单一作用机制方法向基于毒性途径的范例转变，我们设想可以将来自多种技术（例如蛋白质组学、代谢组学、转录组学、支持性 RT-PCR 研究）的毒理基因组学数据结合在一起，以了解受化学品影响的多个、可能相互作用的途径的复杂性，这将影响人类健康风险评估。
