Disclaimer

Monsanto Company has generously consented to the use of the information provided in various of their regulatory submissions for event MON 810 as a training tool. It must be noted, however, that in order to enhance the utility of the case study as a training tool, liberties were taken with the information provided in the original applications. Certain information has been reduced to summaries and the data as presented in the case study are only a subset of that which was actually submitted. The case study in no way constitutes a complete application nor is it to be considered a complete safety assessment. To that end, the use of this information in the form of a training tool does not constitute an endorsement of the information or product nor should it be considered as a reflection of any of the original submissions.

Preface

This teaching module has been developed as a tool for providing regulators with practical training in the safety assessment of transgenic plants. The concepts of risk assessment as discussed in this text do not reflect any one country's regulatory approach, but rather have been modelled after international consensus documents such as those produced by the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations.

In order to provide some indication of the type of data usually presented in support of a safety evaluation, a case study using genetically engineered maize (Zea mays) event MON 810 and its progeny has been developed. The content of the study includes excerpts from applications submitted to regulatory authorities in the European Union, the United Kingdom (UK), Japan, and the United States (US).

Maize line MON 810 (trade name YieldGard®) was developed through a specific genetic modification to be resistant to attack by European corn borer (ECB; Ostrinia nubilalis), a major insect pest of maize in agriculture. The novel variety produces a truncated version of the insecticidal protein, Cry1Ab, derived from Bacillus thuringiensis. Delta-endotoxins, such as the Cry1Ab protein expressed in MON 810, act by selectively binding to specific sites localized on the brush border midgut epithelium of susceptible insect species. Following binding, cation-specific pores are formed that disrupt midgut ion flow and thereby cause paralysis and death. Cry1Ab is insecticidal only to lepidopteran insects, and its specificity of action is directly attributable to the presence of specific binding sites in the target insects. There are no binding sites for delta-endotoxins of B. thuringiensis on the surface of mammalian intestinal cells, therefore, livestock animals and humans are not susceptible to these proteins.

Event MON 810 received its first regulatory approval in the US in 1995 (US Department of Agriculture), and has since been approved for environmental release and use in livestock feed and/or human food from a number of countries including Argentina, Canada, Japan, South Africa, and the European Union (Table 1).

A Note on Quality Standards for Documentation

The evaluation of an application for environmental release is comparable to the peer review of a manuscript for publication in a scientific journal. Accordingly, the quality of the text and data presented must be commensurate with this.

Experimental procedures should be described in sufficient detail (or referenced accordingly) so that the methodology can be repeated. Spelling and usage should be standard and laboratory jargon avoided. It is recommended that international standards for nomenclature be adopted, such as those described in the International Union of Biochemistry and Molecular Biology’s Biochemical Nomenclature and Related Documents (1992) 2nd Ed. Portland Press, Inc., Chapel Hill, NC which contains the International Union of Biochemistry rules of nomenclature for amino acids, peptides, nucleic acids, polynucleotides, vitamins, coenzymes, quinones, folic acid and related compounds, corrinoids, lipids, enzymes, proteins, cyclitols, steroids, carbohydrates, carotenoids, peptide hormones, and human immunoglobulins. Correct chemical names should be given and strains of organisms should be specified. Trade names should be identified. Système International (SI) units and symbols should be used whenever possible.

Illustrations, tables and figures must be clear and legible. Original drawings, high-quality photographs or laser prints are acceptable; poor-quality reproductions that often result from photocopying prints are not. In particular, reproductions of gels or blots must be of sufficient quality to clearly show the described results.