期刊
REGULATORY TOXICOLOGY AND PHARMACOLOGY
卷 56, 期 1, 页码 82-92出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yrtph.2009.09.009
关键词
Decision analysis; QSAR; Teratogenicity; Integrated testing strategies; Test batteries; Uncertainty
资金
- National French Agency for Scientific Research (ANR) [ANR-07-CP2D-03]
The design of toxicological testing strategies aimed at identifying the toxic effects of chemicals without (or with a minimal) recourse to animal experimentation is an important issue for toxicological regulations and for industrial decision-making. This article describes an original approach which enables the design of substance-tailored testing strategies with a specified performance in terms of false-positive and false-negative rates. The outcome of toxicological testing is simulated in a different way than previously published articles on the topic. Indeed, toxicological outcomes are simulated not only as a function of the performance of toxicological tests but also as a function of the physico-chemical Properties of chemicals. The required inputs for Our approach are QSAR predictions for the LOAELs of the toxicological effect of interest and statistical distributions describing the relationship existing between in vivo LOAEL values and results from in vitro tests. Our methodology is able to correctly predict the performance of testing strategies designed to analyze the teratogenic effects of two chemicals: di(2-ethylhexyl)phthalate and Indomethacin. The proposed decision-support methodology can be adapted to any toxicological context as long as a Statistical Comparison between in vitro and in Vivo results is possible and QSAR models for the toxicological effect of interest can be developed. (C) 2009 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据