AstraZeneca, Sodertalje, Sweden.
Reprod Toxicol. 2012 Apr;33(2):155-64. doi: 10.1016/j.reprotox.2011.12.004. Epub 2011 Dec 21.
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.
本报告提供了一个联盟努力开发协调一致的斑马鱼发育毒性测定的进展更新。20 种非专利化合物（10 种动物致畸物和 10 种动物非致畸物）在 4 个实验室中进行了盲法评估。来自池塘来源和养殖型野生型的斑马鱼胚胎暴露于测试化合物 5 天，随后评估其致死率和形态变化。每个测试实验室都与动物数据（60-70%）达到了相似的整体一致性。为了提高整体一致性，随后的优化程序侧重于化合物配方和测试浓度调整、卵壳渗透和重复次数。这些优化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来自池塘来源的斑马鱼胚胎进行了重新测试，总一致性达到 85%。为了进一步评估测定性能，目前正在两个实验室使用来自池塘来源和养殖型野生型斑马鱼的胚胎进行其他化合物的研究。
