Subchronic feeding toxicity studies of drought-tolerant transgenic wheat MGX11-10 in Wistar Han RCC rats

Highlights

• Evaluate the subchronic oral toxicity of genetically modified MGX11-10 wheat.

• MGX11-10 wheat diets did not produce any adverse effects in rats during the study.

• MGX11-10 wheat are considered as safe and nutritious as the non-transgenic wheat.

Abstract

A subchronic toxicity study were conducted in Wistar Han RCC rats to evaluate the potential health effects of genetically modified (GM), drought-tolerant wheat MGX11-10. Rats were fed a rodent diet formulated with MGX11-10 and were compared with rats fed a diet formulated with its corresponding non-transgenic control Jimai22 and rats fed a basal diet. MGX11-10 and Jimai22 were ground into flour and formulated into diets at concentrations of 16.25, 32.5, or 65%, w/w% and fed to rats (10/sex/group) for 13 weeks. Compared with rats fed Jimai22 and the basal-diet group, no biologically relevant differences were observed in rats fed the GM diet with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, clinical chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, the MGX11-10 diets did not cause any treatment-related effects in rats following at least 90 days of dietary administration as compared with rats fed diets with the corresponding non-transgenic control diet and the basal-diet group. The MGX11-10 diets are considered equivalent to the diets prepared from conventional comparators. The results demonstrated that MGX11-10 wheat is as safe and wholesome as the corresponding non-transgenic control wheat.

Introduction

Bread wheat (Triticum aestivum L.) is one of the most important food crops, cultivated on about 220 million ha, providing food to one-third of the global population and providing 20% of the global caloric requirements (Gill BS et al., 2004; Shiferaw B et al., 2013; Rasheed A et al., 2018). The yield of wheat is significantly affected by climatic change and scarcity of water resources in the environment. Drought is one of the environmental stresses that seriously limit crop production in the majority of agriculture fields in the world (Al-Maskri et al., 2016; Lesk, C. et al., 2016; Kulkarni M et al., 2017; Matiu et al., 2017). As a result of climate change, the global frequency and severity of drought events is likely to increase (Shahinnia F et al., 2016). It is estimated that a cereal (maize, rice and wheat) loss of 1820 million Mg has been caused by droughts during the past four decades globally (Leng G, 2019). Drought stress caused a reversible decline in leaf water relations, membrane stability, and photosynthetic activity, leading to increased reactive oxygen species (ROS) generation, lipid peroxidation and membrane injury (Abid M et al., 2018). This phenomenon inhibits further nutrient absorption and affects crop growth, gene expression, distribution, yield and quality (Stendle and Peterson, 1998; Guo R et al., 2018). A way to improve the drought tolerance of crops is to discover new genes and alleles that allow plants to continue to grow and maintain or increase grain yield under water-limited growing conditions.

With the continuous development of transgenic technology, the generalization and application of transgenic crops is progressing rapidly. The methods of modern agricultural biotechnology have been utilized to transfer genes from one organism to another without sexual reproduction and across species. This process allows targeted alterations to be introduced into plant genomes in a more specific and controlled manner and more rapidly than can be achieved through conventional breeding and selection of crops. Wheat event MGX11-10 was genetically modified to improve drought tolerance. The WK gene was cloned from wheat, and the wheat Jimai 22 was used as the transformation receptor. WK gene is a protein kinase gene, WK protein kinase catalyzes phosphorylation of protein, and protein phosphorylation is involved in the transmission of stress signals and plays an important role in improving plant drought tolerance (Zhao, 2015). Genetically modified plants expressing drought-tolerance traits offer a new strategy for crop protection, but at the same time, present a challenge in terms of food safety assessment. Because the methods used to produce crops with biotechnology differ from those used in conventional breeding, numerous scientific organizations have published guidelines for assessing their safety (WHO, 1991 and 1995; FAO, 1996; and OECD, 1993 and 1997). The primary goal established in these guidelines is comparison analysis between the particular genetically modified (GM) crop and the corresponding non-transgenic control crop with an established history of safe use. In most cases, the data necessary to demonstrate that a GM crop is “as safe as” the corresponding non-transgenic control comparator can be determined based on compositional analysis, however, a number of 13 week (i.e., subchronic) rodent toxicology studies have also been conducted with food and feed fractions from GM crops that support their safety (Bai H et al., 2015; Sabitha et al. 2017; Zou S et al., 2018; Sabitha et al. 2018; Qian et al., 2018a; Qian et al., 2018b).

In the present study, we report the results of a 13 week rodent toxicology study conducted with MGX11-10 wheat. This study was conducted in compliance with Chinese guideline on the performance of safety assessment of genetically modified plant and derived products 90-day feeding test in rats（NY/T 1102–2006）at the Experimental Animal Center of the Tianjin Centers for Disease Control and Prevention (Tianjin, China).