Novel Food Information - Maize event MON 87427

Health Canada has notified Monsanto Canada Inc. that it has no objection to the food use of glyphosate tolerant maize event MON 87427. The Department conducted a comprehensive assessment of this variety according to its Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based upon internationally accepted principles for establishing the safety of foods with novel traits.

Background

The following provides a summary of the notification from Monsanto Canada Inc. and the evaluation by Heath Canada and contains no confidential business information.

1. Introduction

Monsanto has developed glyphosate tolerant maize event MON 87427 to have tissue-selective glyphosate tolerance in order to facilitate the production of viable hybrid maize seed. Recombinant DNA techniques were used to confer tolerance to the herbicide glyphosate in the leaves, stalk, root tissues, and tissues that develop into seed or grain and silks, through the expression of the CP4 EPSPS protein. This allows for the production of male-sterile phenotypes, which will reduce or eliminate the need for detasseling in the production of hybrid maize seed.

The safety assessment performed by Food Directorate evaluators was conducted according to Health Canada's Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based on harmonization efforts with other regulatory authorities and reflect international guidance documents in this area (e.g., Codex Alimentarius). The assessment considered: how MON 87427 was developed; how the composition and nutritional quality of MON 87427 compared to non-modified varieties; and the potential for MON 87427 to be toxic or cause allergic reactions. Monsanto Canada Inc. has provided data that demonstrates that MON 87427 maize is as safe and of the same nutritional quality as traditional maize varieties used as food in Canada.

The Food Directorate has a legislated responsibility for pre-market assessment of novel foods and novel food ingredients as detailed in the Food and Drug Regulations (Division 28). Food use of glyphosate tolerant MON 87427 is considered a novel food under the following part of the definition of novel foods: "c) a food that is derived from a plant, animal or microorganism that has been genetically modified such that

1. the plant, animal or microorganism exhibits characteristics that were not previously observed in that plant, animal or microorganism."

2. Development of the Modified Plant

The petitioner has provided information describing the methods used to develop glyphosate tolerant maize MON 87427 and the molecular biology data that characterize the genetic change, which results in tissue-selective glyphosate tolerance that facilitates the production of hybrid maize seed. The tissue-selective glyphosate tolerance in MON 87427 maize was achieved using a specific promoter and intron combination.

Glyphosate tolerant maize MON 87427 was genetically modified using Agrobacterium-mediated transformation of a proprietary conventional maize line, LH198 x HiII, with vector PV-ZMAP1043. The transforming plasmid contains one transfer DNA (T-DNA) consisting of the cp4 epsps coding sequence from Agrobacterium sp. strain CP4 which is under the regulation of the e35S promoter from the cauliflower mosaic virus, the hsp70 intron from the maize heat shock protein 70 gene, the CTP2 targeting sequence from Arabidopsis thaliana, and the nos 3' nontranslated region from Agrobacterium tumefaciens.

3. Characterization of the Modified Plant

Southern blot analysis and DNA sequencing of glyphosate tolerant maize MON 87427 demonstrated the presence of a single copy of the T-DNA inserted at a single site and at a single locus of the maize genome. Southern blot analysis confirmed the absence of any plasmid backbone DNA in glyphosate tolerant maize MON 87427. DNA sequencing analysis of the insert and the flanking genomic DNA confirmed the arrangement and linkage of the various elements within the insert.

The stability of the inserted T-DNA was evaluated through five different generations. The results of Southern blot analysis and segregation data demonstrated the stability of glyphosate tolerant maize MON 87427 at the genomic level as well as the segregation of the trait according to Mendelian inheritance principles.

4. Product Information

The tissue-selective glyphosate tolerance in MON 87427 maize was achieved using a specific promoter and intron combination to drive CP4 EPSPS protein expression in vegetative and female reproductive tissues, which conferred tolerance to glyphosate in the leaves, stalk, and root tissues and tissues that develop into seed or grain and silks. This specific promoter and intron combination also results in limited or no production of CP4 EPSPS protein in two key male reproductive tissues: pollen microspores, which develop into pollen grains, and tapetum cells that supply nutrients to the pollen. The detasseling of maize varieties, which is a very labour intensive task in the production of hybrid maize, is greatly reduced, or no longer necessary as the application of glyphosate herbicide will effectively prevent the self-pollination of maize. Increased expression of CP4 EPSPS in select vegetative and female reproductive tissues will produce a female parent, following application of a glyphosate herbicide, for the production of hybrid maize seed.

5. Dietary Exposure

The genetic modification of MON 87427 maize is not intended to alter any of its nutritional aspects. Therefore, the use of MON 87427 maize and products derived from it will be similar to traditional maize varieties. The introduction of MON 87427 in hybrid maize seed production fields is not anticipated to result in a change in the dietary intake of maize and maize-derived products.

6. Nutrition

The nutrient data was obtained from test (MON 87427), control (LH198 x LH287) and commercial corn varieties (reference varieties) grown in 2008 at three USA locations in a randomized complete block design with three plots for each test, control and reference varieties. MON 87427 plots received glyphosate herbicide, as per protocol. Analytical data from the reference varieties were combined across all sites and used to establish a 99% tolerance interval for each composition component for commercial maize.

Nutrients, anti-nutrients and secondary metabolites were analyzed in grain, as follows: Proximate(s): moisture, crude protein, crude fat, crude fibre, ash, carbohydrates (calculated); plus acid detergent fibre (ADF), neutral detergent fibre (NDF); Fatty Acid(s): C8-C22; Amino Acid(s): asparagine, threonine, serine, glutamic acid, proline, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, lysine, arginine, tryptophan; Mineral(s): calcium, copper, iron, magnesium, manganese, phosphorous, potassium, sodium, zinc; Vitamin(s): folic acid, niacin, vitamin A (beta carotene), vitamin B1, vitamin B2, vitamin B6, vitamin E; Anti-nutrient(s): phytic acid, raffinose; Secondary Metabolites: furfural, ferulic acid, p-coumaric acid and, in forage, as follows: Proximates: moisture, crude protein, crude fat, crude fibre, ash, carbohydrates (calculated); plus acid detergent fibre (ADF), neutral detergent fibre (NDF); Minerals: calcium and phosphorous.

For the combined locations, statistical differences in test (MON 87427) vs. control (LH198 x LH827) were noted in 7 analytes. For nutrients, anti-nutrients and/or secondary metabolites where a statistical difference was determined, all mean values were within the 99% tolerance interval and/or literature ranges.

All field trial experiments used to test MON 87427 tissue-selective glyphosate herbicide tolerant maize were acceptable. All analyses of test, control and reference varieties were done using approved scientific and appropriate statistical methods.

The nutrient composition of tissue-selective glyphosate herbicide tolerant maize (MON 87427) has been shown to be similar to conventional, commercial maize.

7. Chemistry/Toxicology

The source of the cp4 epsps gene is a microorganism (Agrobacterium sp strain CP4) which is not known to cause human toxicity or allergy. It was noted that EPSPS protein is naturally found in plants and fungi, and humans have a history of exposure to EPSPS through their normal diets, with no associated toxicities. Previously, Health Canada has stated no objection to the use of CP4 EPSPS in corn, cotton, canola, and soybean transgenic lines for human food applications in Canada.

The daily exposure to CP4 EPSPS protein from this maize line combined with the results of an acute oral toxicity assay in mice indicate a relatively large margin of exposure and a very low potential for toxicity for CP4 EPSPS. Further, the results of a simulated gastric fluid study indicate any ingested CP4 EPSPS protein is likely readily digested in the acidic environment of the stomach. CP4 EPSPS does not have sequence homology to any known toxins or allergens. Overall, because CP4 EPSPS is present in low concentration, readily digested, and lacks sequence homology with known toxins or antinutrients or allergens, it is improbable that CP4 EPSPS would behave as a toxin or an allergen in the human system.

Since corn does not contain endogenous toxins or a priority allergen, the modification in MON 87427 maize would not be expected to create additional toxic or allergenic risks.

Food products derived from MON 87427 maize would not be associated with any greater toxicological or allergenic risk to consumer health than food products derived from conventional maize currently available in the Canadian market.

Conclusion

Health Canada's review of the information presented in support of the food use of glyphosate tolerant maize line MON 87427 does not raise concerns related to food safety. Health Canada is of the opinion that food derived from MON 87427 maize is as safe and nutritious as food from current commercial maize varieties.

Health Canada's opinion deals only with the food use of glyphosate tolerant maize MON 87427. Issues related to its use as animal feed have been addressed separately through existing regulatory processes in the Canadian Food Inspection Agency (CFIA). From their assessment, the CFIA concluded that there are no concerns from an environmental and feed safety perspective. This perspective is applicable to the food and feed products derived from glyphosate tolerant maize MON 87427 destined for commercial sale.

This Novel Food Information document has been prepared to summarize the opinion regarding the subject product provided by the Food Directorate, Health Products and Food Branch, Health Canada. This opinion is based upon the comprehensive review of information submitted by the petitioner according to the Guidelines for the Safety Assessment of Novel Foods.

For further information, please contact:

Novel Foods Section
Food Directorate
Health Products and Food Branch
Health Canada, PL2204A1
251 Frederick Banting Driveway
Ottawa, Ontario K1A 0K9
novelfoods-alimentsnouveaux@hc-sc.gc.ca