Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Systemic Physiological and Ecotoxicological Research (SPHERE), Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen, Belgium.
Int J Mol Sci. 2019 Mar 23;20(6):1472. doi: 10.3390/ijms20061472.
In Europe, the toxicological safety of genetically modified (GM) crops is routinely evaluated using rodent feeding trials, originally designed for testing oral toxicity of chemical compounds. We aimed to develop and optimize methods for advancing the use of zebrafish feeding trials for the safety evaluation of GM crops, using maize as a case study. In a first step, we evaluated the effect of different maize substitution levels. Our results demonstrate the need for preliminary testing to assess potential feed component-related effects on the overall nutritional balance. Next, since a potential effect of a GM crop should ideally be interpreted relative to the natural response variation (i.e., the range of biological values that is considered normal for a particular endpoint) in order to assess the toxicological relevance, we established natural response variation datasets for various zebrafish endpoints. We applied equivalence testing to calculate threshold equivalence limits (ELs) based on the natural response variation as a method for quantifying the range within which a GM crop and its control are considered equivalent. Finally, our results illustrate that the use of commercial control diets (CCDs) and null segregant (NS) controls (helpful for assessing potential effects of the transformation process) would be valuable additions to GM safety assessment strategies.
在欧洲，转基因（GM）作物的毒理学安全性通常使用啮齿动物喂养试验进行评估，这些试验最初是为了测试化学化合物的口服毒性而设计的。我们旨在开发和优化使用斑马鱼喂养试验来评估 GM 作物安全性的方法，以玉米作为案例研究。在第一步中，我们评估了不同玉米替代水平的影响。我们的结果表明，需要进行初步测试，以评估潜在的饲料成分对整体营养平衡的影响。接下来，由于 GM 作物的潜在影响理想情况下应相对于自然反应变异（即，对于特定终点被认为是正常的生物值范围）进行解释，以评估毒理学相关性，因此我们为各种斑马鱼终点建立了自然反应变异数据集。我们应用等效性测试来计算基于自然反应变异的阈值等效极限（EL），作为量化 GM 作物及其对照被认为等效的范围的方法。最后，我们的结果表明，使用商业对照饲料（CCD）和空分（NS）对照（有助于评估转化过程的潜在影响）将是 GM 安全评估策略的有价值的补充。
