Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era
Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era
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DOI：
10.1016/j.taap.2010.03.019
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发表时间：
2013-09-15
影响因子：
3.8
通讯作者：
Subramaniam, Ravi P.
中科院分区：
文献类型：
--
作者：
Chiu, Weihsueh A.;Euling, Susan Y.;Subramaniam, Ravi P.
基因组学和相关技术对环境化学品的人类健康风险评估的贡献主要集中在阐明毒性机制上，这一点在本期的其他文章中有所讨论。然而，人们有兴趣超越危险特性，对定量风险评估（QRA）产生更直接的影响，即，确定毒性值，以制定接触标准和清除值。我们建议，在后基因组时代的环境化学品的QRA的演变将涉及三个，有点重叠的阶段，不同类型的方法开始成熟。最初的重点（在第一阶段）一直是并将继续是“增强”的证据权重，使用基因组和相关技术定性，以增加信心和QRA的结果的科学基础。旨在将这些数据与传统的基于动物的方法（特别是定量预测因子或替代因子）“整合”，以用于其所锚定的体内毒性数据的努力现在才刚刚开始探索（在第II阶段）。与此同时，人们认识到需要“扩大”使用已建立的人类疾病和病症的易感性或风险的生物标志物用于QRA，特别是用于解决累积评估和群体风险的问题。最终（在第三阶段），可以通过开发新的分子和基于途径的生物标志物以及统计和二氧化硅模型来实现实质性的进一步进展，这些模型建立在对人类疾病和障碍途径的理解的预期进展基础上。这些努力将有助于质量和风险评估逐步“调整方向”，使其采取更直接地将环境暴露与人类后果联系起来的办法。爱思唯尔公司出版。
The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA) - i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on "augmentation" of weight of evidence using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards "integration" of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for "expansion" of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silica models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual "reorientation" of QRA towards approaches that more directly link environmental exposures to human outcomes. Published by Elsevier Inc.