From alternative methods to a new toxicology
From alternative methods to a new toxicology
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DOI：
10.1016/j.ejpb.2010.12.027
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发表时间：
2011-04-01
影响因子：
4.9
通讯作者：
Hartung, Thomas
中科院分区：
文献类型：
--
作者：
Hartung, Thomas
机制毒理学的发展在很大程度上依赖于替代或补充传统动物试验的方法。过去几十年的生物技术和信息学革命已经使这些技术广泛可用和有用，但监管毒理学一直缓慢接受这些新方法。然而，主要的验证工作已经提供了证据，证明新方法不会降低安全标准，并且可以整合到监管安全评估中。特别是在欧盟，政治压力，如REACH立法和化妆品立法第7修正案，促使了新方法的需求。在美国，NRC的远景报告呼吁建立一个世纪毒理学（以及EPA最近对其毒性测试策略的适应）已经引发了关于如何创建基于人类细胞培养物、较低物种、高通量测试和建模的新方法的辩论。和接受替代方法支持创建一个新的方法的基础上确定的毒性途径。需要通过循证毒理学（EBT）对当前实践进行概念指导和客观评估。EBT是以循证医学为模型的，它已经证明，对当前实践的严格系统评价和研究的荟萃分析提供了强大的工具，为医疗保健专业人员和患者提供了当前最好的科学证据。同样，一个门户网站的毒理学方法和工具的定量荟萃分析的数据承诺，作为一个新的监管毒理学的大门。(C)2011 Elsevier B.V.保留所有权利。
Mechanistic toxicology has evolved by relying, to a large extent, on methodologies that substitute or complement traditional animal tests. The biotechnology and informatics revolutions of the last decades have made such technologies broadly available and useful, but regulatory toxicology has been slow to embrace these new approaches. Major validation efforts, however, have delivered the evidence that new approaches do not lower safety standards and can be integrated into regulatory safety assessments.Particularly in the EU, political pressures, such as the REACH legislation and the 7th Amendment to the cosmetic legislation, have prompted the need of new approaches. In the US, the NRC vision report calling for a toxicology for the 21st century (and its most recent adaptation by EPA for their toxicity testing strategy) have initiated a debate about how to create a novel approach based on human cell cultures, lower species, high-throughput testing, and modeling.Lessons learned from the development, validation, and acceptance of alternative methods support the creation of a new approach based on identified toxicity pathways. Conceptual steering and an objective assessment of current practices by evidence-based toxicology (EBT) are required. EBT is modeled on evidence-based medicine, which has demonstrated that rigorous systematic reviews of current practices and meta-analyses of studies provide powerful tools to provide health care professionals and patients with the current best scientific evidence. Similarly, a portal for high-quality reviews of toxicological approaches and tools for the quantitative meta-analyses of data promise to serve as door opener for a new regulatory toxicology. (C) 2011 Elsevier B.V. All rights reserved.