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首页> 外文期刊>Reproductive toxicology >Zebrafish developmental toxicity assay: A fishy solution to reproductive toxicity screening, or just a red herring?
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Zebrafish developmental toxicity assay: A fishy solution to reproductive toxicity screening, or just a red herring?

机译：斑马鱼发育毒性试验：用于生殖毒性筛查的鱼腥溶液，还是只是红鲱鱼？

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The zebrafish embryotoxicity/teratogenicity assay is described as a useful alternative screening model to evaluate the effect of drugs on embryofoetal development. Fertilized eggs were exposed to different concentrations of 15 compounds with teratogenic (8) and non-teratogenic (7) potential until 96h post-fertilization when 28 morphological endpoints and the level of compound uptake was assessed. The majority of drugs testing positive in mammals was also positive in zebrafish (75% sensitivity), while a relative high number of false positives were noted (43% specificity). Compound uptake determination appears useful for clarifying classifications as teratogenic or potential overdose although assay sensitivity could be improved to 71% if the exposure threshold, previously suggested as approximately 50ng/larvae, is reconsidered. The zebrafish assay shows some potential, though limited in its current form, as a screening tool for developmental toxicity within Janssen drug development. Further assay refinement with respect to endpoints and body burden threshold is required.
机译：斑马鱼胚胎毒性/致畸性测定被描述为评估药物对胚胎足发育影响的有用的筛选模型。受精卵暴露于不同浓度的15种具有致畸（8）和非致畸（7）潜力的化合物，直到受精后96小时评估28个形态学终点和化合物摄取水平。在哺乳动物中检测出阳性的大多数药物在斑马鱼中也呈阳性（敏感性为75％），而注意到相对较高数量的假阳性（特异性为43％）。化合物摄入量的测定对于阐明致畸性或潜在的过量用药似乎是有用的，尽管如果重新考虑先前建议的接触阈值（约50ng /幼虫），则测定灵敏度可提高至71％。斑马鱼测定法显示出一些潜力，尽管目前形式有限，但可以作为Janssen药物开发中发育毒性的筛选工具。需要对终点和身体负荷阈值进行进一步的分析改进。

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