toxicity testing in the 21st century: a vision and a strategy
来源： 浏览量：1364 更新日期：2010年8月29日
点击下载此文件:/uploads/edit/pdf/2010-8/201008291857176032622.pdf
With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a
Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the
way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and
decreased animal usage by transitioning from current expensive and lengthy in vivo testing
with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines
using robotic high-throughput screening with mechanistic quantitative parameters. Risk
assessment in the exposed human population would focus on avoiding significant perturbations
in these toxicity pathways. Computational systems biology models would be implemented
to determine the dose-response models of perturbations of pathway function.
Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be
based on pharmacokinetic models for the given exposure condition. This practice would
enhance human relevance of test results, and would cover several test agents, compared to
traditional toxicological testing strategies. As all the tools that are necessary to implement
the vision are currently available or in an advanced stage of development, the key prerequisites
to achieving this paradigm shift are a commitment to change in the scientific community,
which could be facilitated by a broad discussion of the vision, and obtaining
necessary resources to enhance current knowledge of pathway perturbations and pathway
assays in humans and to implement computational systems biology models. Implementation
of these strategies would result in a new toxicity testing paradigm firmly based on
human biology.