The zebrafish has been widely used as a predictive model in safety and toxicology. Low cost high-throughput screening can be achieved with this model, and the genome contains orthologues of the majority of human disease genes. However, previous studies indicate that the predictivity of the zebrafish model in toxicology varies between compound and compound class. We examined this issue by screening 24 compounds from two different compound classes, metals and biocides (pesticides/insecticides) for toxicity in the zebrafish model and looked at the effects on hatching, morphology and predictivity for mammalian toxicity. Wild-type zebrafish embryos were exposed to test compounds in 96-well plates for 96 hours starting at 24 hours post fertilization. Hatching was either delayed or accelerated depending on the compound. Three types of alteration in behavioural responses were noted: (i) hypoactivity; (ii) hyperactivity; and (iii) biphasic response (a dose-dependent shift between hypo- and hyperactivity). LC 50 of compounds was calculated and compared to published LD 50 values in rodents. The zebrafish-rodent values were poorly correlated for both metals and biocides. We conclude that, although the zebrafish is a good model for some aspects of toxicology, its predictivity for mammalian toxicity needs to be determined per compound class.

中文翻译：

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农药和金属对斑马鱼胚胎发育和幼虫运动能力的影响

斑马鱼已被广泛用作安全性和毒理学的预测模型。使用该模型可以实现低成本的高通量筛选，并且基因组包含大多数人类疾病基因的直向同源物。但是，先前的研究表明，斑马鱼模型在毒理学方面的可预测性在化合物和化合物类别之间有所不同。我们通过从两种不同的化合物类别（金属和杀生物剂（农药/杀虫剂）中筛选出24种化合物）对斑马鱼模型的毒性进行了研究，并研究了其对孵化，形态和哺乳动物毒性预测性的影响。从受精后24小时开始，将野生型斑马鱼胚胎暴露于96孔板的测试化合物中96小时。取决于化合物，孵化被延迟或加速。注意到行为反应的三种类型的改变：（i）机能减退；（ii）多动症；（iii）两相反应（过度活跃和过度活跃之间的剂量依赖性转变）。计算化合物的LC 50并与在啮齿动物中发表的LD 50值进行比较。金属和杀生物剂的斑马鱼-啮齿动物值相关性很低。我们得出的结论是，尽管斑马鱼是毒理学某些方面的好模型，但仍需按化合物类别确定其对哺乳动物毒性的可预测性。