Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay - Progress report on phase I

Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay - Progress report on phase I
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DOI:
10.1016/j.reprotox.2011.12.004
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发表时间:
2012-04-01
影响因子:
3.3
通讯作者:
Augustine-Rauch, K. A.
Augustine-Rauch, K. A.
中科院分区:
医学4区
文献类型:
--
作者:
Gustafson, A. -L.;Stedman, D. B.;Augustine-Rauch, K. A.

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本报告提供了一个联盟努力开发统一的斑马鱼发育毒性测试的最新进展。20个非专利化合物(10个动物致畸物质和10个动物非致畸物质)在4个实验室进行了盲法评价。来自池塘和养殖品系野生类型的斑马鱼胚胎暴露在测试化合物中5天,随后评估其致死性和形态变化。每个测试实验室与动物数据的总体一致性相似(60%-70%)。随后的优化程序以提高总体一致性为重点,重点是化合物配方和测试浓度调整、绒毛膜渗透和重复次数。这些优化的程序被整合到一个修订的方案中,所有化合物都在一个实验室中使用池塘斑马鱼的胚胎进行了重新测试,获得了85%的总一致性。为了进一步评估化验性能,目前两个实验室正在进行一项额外化合物的研究,使用池塘衍生和培育的野生类型斑马鱼的胚胎。(C)2011 Elsevier Inc.保留所有权利。
This report provides a progress update of a consortium effort to develop a harmonized zebrafish developmental toxicity assay. Twenty non-proprietary compounds (10 animal teratogens and 10 animal non-teratogens) were evaluated blinded in 4 laboratories. Zebrafish embryos from pond-derived and cultivated strain wild types were exposed to the test compounds for 5 days and subsequently evaluated for lethality and morphological changes. Each of the testing laboratories achieved similar overall concordance to the animal data (60-70%). Subsequent optimization procedures to improve the overall concordance focused on compound formulation and test concentration adjustments, chorion permeation and number of replicates. These optimized procedures were integrated into a revised protocol and all compounds were retested in one lab using embryos from pond-derived zebrafish and achieved 85% total concordance. To further assess assay performance, a study of additional compounds is currently in progress at two laboratories using embryos from pond-derived and cultivated-strain wild type zebrafish. (C) 2011 Elsevier Inc. All rights reserved.