Toxicity testing in the 21st century: implications for human health risk assessment.
Toxicity testing in the 21st century: implications for human health risk assessment.
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DOI：
10.1111/j.1539-6924.2008.01168.x
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Tice RR
中科院分区：
文献类型：
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作者：
Kavlock RJ;Austin CP;Tice RR
丹尼尔克鲁斯基及其同事的风险分析观点阐述了国家研究理事会委员会（1）制定的长期愿景和战略计划，该委员会由美国环境保护署（EPA）赞助，并得到美国国家毒理学计划（NTP）的支持，以“推进环境因子的毒性测试和人类健康评估实践”。这一愿景的组成部分包括：化学表征;使用基于人类细胞的高通量分析，涵盖毒性途径的多样性;使用动物进行有针对性的测试，以填补数据空白;剂量反应和外推建模;以及生成和使用基于人群和人类接触的数据，以解释毒性测试的结果。该战略计划认识到，实现这一愿景将需要在十年或更长时间内开展重大研究工作，以确定所有重要的毒性途径，并且必须明确区分哪些途径干扰是真正有害的（即可能导致人类健康不良后果），哪些不是。Krewski等人指出，在合理的时间范围内（即几十年）实现这一愿景将需要一个跨学科研究机构的参与，该研究机构将主要由美国联邦政府协调和资助，并将促进适当的校内和校外研究。预计这种方法将大大增加可供测试的化合物数量，同时提供与进行人类健康风险评估更直接相关的数据。NTP通过其路线图，1美国国立卫生研究院（NIH）化学基因组学中心（NCGC）通过分子图书馆倡议，2和EPA通过其ToxCast™计划3及其未来毒性测试战略计划草案，分别认识到需要将创新引入化学品毒理学活性评估，并且每个人都在这方面取得了进展。然而，Krewski等人提出的巨大挑战需要在毒理学和风险评估领域无与伦比的努力。出版商免责声明：免责声明：虽然本报告中描述的研究已经由一个或多个参与的联邦机构资助，但本报告并不一定反映相应组织的观点1 http：//ntp-server. niehs。nih。gov/？objectid= EE4AED80-F1F6-975E-7317D7CB17625A15 2 http：//www.国家地理信息中心。nih。政府/
The risk analysis perspective by Daniel Krewski and colleagues lays out the long-term vision and strategic plan developed by a National Research Council committee (1), sponsored by the US Environmental Protection Agency (EPA) with support from the US National Toxicology Program (NTP), to “advance the practices of toxicity testing and human health assessment of environmental agents.” Components of the vision include chemical characterization; the use of human cell-based, high-throughput assays that cover the diversity of toxicity pathways; targeted testing using animals to fill in data gaps; doseresponse and extrapolation modeling; and the generation and use of population-based and human exposure data for interpreting the results of toxicity tests. The strategic plan recognizes that meeting this vision will require a major research effort conducted over a period of a decade or more to identify all of the important toxicity pathways, and that a clear distinction must be made between which pathway perturbations are truly adverse (ie, would likely lead to adverse health outcomes in humans) and those that are not. Krewski et al. note that achieving this vision in a reasonable time frame (ie, decades) would require the involvement of an interdisciplinary research institute that would be coordinated and funded primarily by the US Federal government and which would foster appropriate intramural and extramural research. It is expected that this approach would greatly increase the number of compounds that can be tested, while providing data more directly relevant for conducting human health risk assessment. The NTP though its Roadmap, 1 the National Institutes of Health (NIH) Chemical Genomics Center (NCGC) through the Molecular Libraries Initiative, 2 and the EPA through its ToxCast™ program3 and its draft Strategic Plan for the Future of Toxicity Testing have individually recognized the need to bring innovation into the assessment of the toxicological activity of chemicals, and each has made progress in doing so. However, the grand challenge put forth by Krewski et al. requires an effort unparalleled in the field of toxicology and risk assessment.Publisher's Disclaimer: Disclaimer: Although the research described in this report has been funded by one or more of the participating federal agencies, the report does not necessarily reflect the views of the respective organizations 1 http://ntp-server. niehs. nih. gov/? objectid= EE4AED80-F1F6-975E-7317D7CB17625A15 2 http://www. ncgc. nih. gov/