title: Variability of control data and relevance of observed group differences in five oral toxicity studies with genetically modified maize MON810 in rats.
abstract: 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.
authors.affiliation: BioMath GmbH, Schnickmannstr. 4, 18055, Rostock, Germany. kerstin.schmidt@biomath.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: BioMath GmbH, Schnickmannstr. 4, 18055, Rostock, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
authors.affiliation: BioMath GmbH, Schnickmannstr. 4, 18055, Rostock, Germany.|University of Hohenheim, Biostatistics (340c), Fruwirthstr. 23, 70599, Stuttgart, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Schmidt
authors.affiliation: Institute for Biosafety in Plant Biotechnology, Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Erwin-Baur-Str. 27, 06484, Quedlinburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kohl
authors.affiliation: Institute for Biosafety in Plant Biotechnology, Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Erwin-Baur-Str. 27, 06484, Quedlinburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Wilhelm
authors.affiliation: Institute for Biosafety in Plant Biotechnology, Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Erwin-Baur-Str. 27, 06484, Quedlinburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Schiemann
authors.affiliation: Wageningen UR Biometris, Postbus 16, 6700 AA, Wageningen, The Netherlands.
authors.forename: Hilko
authors.initials: H
authors.lastname: van der Voet
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173, Hannover, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
mesh_terms: D000821:Animal Feed; D000818:Animals; D001835:Body Weight; D005260:Female; D030841:Food, Genetically Modified / Q000633:toxicity*; D016014:Linear Models; D008297:Male; D009929:Organ Size; D030821:Plants, Genetically Modified / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods; D003313:Zea mays / Q000235:genetics*
keywords: 90-day toxicity study; Consistency; Genetically modified plants; Historical control data; Linear mixed models; Maize; Risk assessment; Standardized effect sizes; Statistical power