Schmidt Kerstin, Schmidtke Jörg, Schmidt Paul, Kohl Christian, Wilhelm Ralf, Schiemann Joachim, van der Voet Hilko, Steinberg Pablo
BioMath GmbH, Schnickmannstr. 4, 18055, Rostock, Germany.
University of Hohenheim, Biostatistics (340c), Fruwirthstr. 23, 70599, Stuttgart, Germany.
Arch Toxicol. 2017 Apr;91(4):1977-2006. doi: 10.1007/s00204-016-1857-x. Epub 2016 Oct 11.
The data of four 90-day feeding trials and a 1-year feeding trial with the genetically modified (GM) maize MON810 in Wistar Han RCC rats performed in the frame of EU-funded project GRACE were analysed. Firstly, the data obtained from the groups having been fed the non-GM maize diets were combined to establish a historical control data set for Wistar Han RCC rats at the animal housing facility (Slovak Medical University, Bratislava, Slovakia). The variability of all parameters is described, and the reference values and ranges have been derived. Secondly, the consistency of statistically significant differences found in the five studies was analysed. In order to do so, the body weight development, organ weight, haematology and clinical biochemistry data were compared between the studies. Based on the historical control data, equivalence ranges for these parameters were defined, and the values measured in the GM maize-fed groups were compared with these equivalence ranges. Thirdly, the (statistical) power of these feeding studies with whole food/feed was assessed and detectable toxicologically relevant group differences were derived. Linear mixed models (LMM) were applied, and standardized effect sizes (SES) were calculated in order to compare different parameters as well as to provide an overall picture of group and study differences at a glance. The comparison of the five feeding trials showed a clear study effect in the control data. It also showed inconsistency both in the frequency of statistically significant differences and in the difference values between control and test groups.
对欧盟资助项目GRACE框架下用转基因玉米MON810对Wistar Han RCC大鼠进行的四项90天喂养试验和一项1年喂养试验的数据进行了分析。首先，将喂食非转基因玉米日粮组获得的数据合并，以建立动物饲养设施（斯洛伐克布拉迪斯拉发斯洛伐克医科大学）中Wistar Han RCC大鼠的历史对照数据集。描述了所有参数的变异性，并得出了参考值和范围。其次，分析了五项研究中发现的统计学显著差异的一致性。为此，比较了各研究之间的体重发育、器官重量、血液学和临床生物化学数据。根据历史对照数据，定义了这些参数的等效范围，并将转基因玉米喂养组测得的值与这些等效范围进行比较。第三，评估了这些全食物/饲料喂养研究的（统计）功效，并得出了可检测到的毒理学相关组间差异。应用线性混合模型（LMM），并计算标准化效应大小（SES），以便比较不同参数，并一眼看出组间和研究间差异的总体情况。五项喂养试验结果表明，对照数据存在明显的研究效应。同时也表明，对照组和试验组之间在统计学显著差异的频率和差异值方面均存在不一致。
