Novel Food Information - Improved Fatty Acid Profile Soybean MON 87705

Health Canada has notified Monsanto Canada Inc. that it has no objection to the food use of Improved Fatty Acid Profile Soybean MON 87705. 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 Improved Fatty Acid Profile Soybean MON 87705 using recombinant DNA techniques to selectively down regulate two enzymes, FATB and FAD2, involved in the soybean seed fatty acid biosynthetic pathway. The genetic modification results in RNA suppression of FATB1-A and FAD2-1A transcripts which leads to a change in the fatty acid profile in the soybean seed. MON 87705 has an improved fatty acid profile similar to that of canola oil and olive oil, consisting of increased monounsaturated and reduced polyunsaturated and saturated fatty acid levels relative to conventional soybean

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 87705 was developed; how the composition and nutritional quality of MON 87705 compared to non-modified varieties; and the potential for MON 87705 to be toxic or cause allergic reactions. Monsanto Canada Inc. has provided data that demonstrates that MON 87705 soybeans are as safe and of the same nutritional quality as traditional soybean 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 Improved Fatty Acid Profile Soybean MON 87705 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

• iii. one or more characteristics of the plant, animal or microorganism no longer fall within the anticipated range for that plant, animal or microorganism."

2. Development of the Modified Plant

The petitioner has provided information describing the methods used to develop Improved Fatty Acid Profile Soybean MON 87705 and the molecular biology data that characterize the genetic change, which results in soybean oil with an unsaturated fatty acid profile similar to olive oil and canola oil, while having less than half the levels of saturated fatty acids of conventional soybean oil. This phenotype was achieved by RNA suppression of the FATB1-A and FAD2-1A transcripts. This soybean line includes two expression cassettes containing segments of the endogenous FATB1-A and FAD2-1A genes as well as the cp4 epsps gene and all their associated regulatory elements.

Improved Fatty Acid Profile Soybean MON 87705 was genetically modified using Agrobacterium-mediated transformation of commercial soybean variety A3525 with the transformation vector PV-GMPQ/HT4404. The transformation vector PV-GMPQ/HT4404 carried two separate transfer DNA (T-DNA I and T-DNA II) sequences, comprised of an expression cassette containing FATB1-A and FAD2-1A sense segments, a cp4 epsps expression cassette and 7S-alpha seed promoter (T-DNA I) and containing FATB1-A and FAD2-1A antisense segments, FMV/TsF1 promoter and plastid targeting sequence (T-DNA II).

3. Characterization of the Modified Plant

Southern blot analysis and DNA sequencing of Improved Fatty Acid Profile Soybean MON 87705 demonstrated the presence of a single copy of both T-DNA's inserted at a single site and at a single locus of the soybean genome. Southern blot analysis confirmed the absence of any plasmid backbone DNA in Improved Fatty Acid Profile Soybean MON 87705.

Northern blot analysis confirmed the suppression of the production of the FAD2-1A and FATB1-A RNA with noticeable differences in hybridization signals between conventional soybean and MON87705 soybean.

The stability of the inserted T-DNA's was evaluated through four different generations. The results of Southern blot analysis and segregation data demonstrated the stability of Improved Fatty Acid Profile Soybean MON 87705 at the genomic level.

4. Product Information

Improved Fatty Acid Profile Soybean MON 87705 differs from its traditional counterpart by the suppression of two endogenous soybean enzymes, FATB and FAD2. The insertion of the FATB1-A and FAD2-1A gene segments assembled in a suppression cassette under the control of a seed promoter limits the change in fatty acid profile to the seed only.

The components of the FAD2-1A and FATB1-A genes found in T-DNA 1 and 2 are endogenous soybean sequences which were selectively chosen to produce a double stranded RNA complex that down regulates expression of the desired fatty acids using the naturally occurring cellular phenomena of RNA suppression. The cp4 epsps coding region was obtained from Agrobacterium sp strain CP4.

5. Dietary Exposure

Soybean is the main source of plant protein consumed by humans and is the second leading source of vegetable oil of all food crops produced in the world. Soybean can be processed into a wide variety of food products such as oil, soybean protein products, and whole soybean foods. Soybean oil can be used in the manufacture of cooking oils, shortening, margarine, mayonnaise, and salad dressings. The petitioner has indicated that MON 87705 soybean is intended primarily for use as a broad acre field soybean and not for vegetable or garden soybeans that are generally used to produce tofu, soybean sprouts, soymilk, edamame or other similar food items.

6. Nutrition

MON 87705 has an improved fatty acid profile similar to that of canola oil and olive oil, consisting of increased monounsaturated and reduced polyunsaturated and saturated fatty acid levels relative to conventional soybean.

In order to determine the nutritional similarity of MON 87705 to conventional soybean, three field trials were conducted at three locations: Chile 2007, US 2007, and US 2008. All analyses of test and control soybean lines were performed using approved scientific and appropriate statistical methods.

Nutrients and/or anti-nutrients were analyzed, in forage, including: proximates, fibre and, in seed, including: proximates, fibre, amino acids, fatty acids, vitamin E, lectin, trypsin inhibitor, phytic acid, raffinose, stachyose, isoflavones and, in meal, including: proximates, fibre, amino acids, trypsin inhibitor, phytic acid and, in soy protein isolate, including: moisture, amino acids and, in oil, including: fatty acids, vitamin E, lecithin (phospholipids).

In each of the three studies, statistical differences between the control and MON 87705 were noted in 11, 17, and 17 analytes, respectively; however, no trends were noted between the statistical differences and all values were within literature ranges for conventional soybean, with the exception of some fatty acids, as expected.

The fatty acid composition of MON 87705 soybean line consists of approximately 76% oleic acid (monounsaturated), an increase from 17-30% found in conventional soybean. This is comparable to oleic acid content of canola (51-70%) and olive oil (55-83%). There is a significant decrease in linoleic acid (polyunsaturated) levels from 48-59% to approximately 10% in MON 87705. Furthermore, MON 87705 contains only 6% of palmitic and stearic acids in comparison to 10-19% found in conventional soybean, 4-10% in canola, and 8-25% in olive oil.

The nutrient composition of MON 87705 is similar to conventional soybean, with the only difference being the intended changes in the fatty acid profile of MON 87705.

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. EPSPS protein is naturally found in plants and fungi, and humans have a history of safe exposure to EPSPS in our diets. Health Canada has previously stated no objection to the sale of CP4 EPSPS protein-containing corn, cotton, canola, sugarbeet, alfalfa and soybean transgenic lines for human food applications in Canada.

The exposure to CP4 EPSPS protein from this soybean line is negligible, since the amount of this protein in the soybean is very small (0.031% of the total protein content). 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 did not have sequence homology to any known toxins or antinutrients 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 antinutrient or behave as an allergen in the human system.

The RNAi gene segments introduced into MON 87705 soybean produce double-stranded RNA products which are targeted for degradation and do not generate any novel proteins. Furthermore, RNAi and its double-stranded RNA products are normal constituents of food and therefore have a history of safe exposure in the human diet. Thus, RNAi and its products in MON 87705 soybean will not impact on dietary or toxin or allergen exposure in consumers who ingest MON 87705 soybean.

The possibility of alterations to endogenous allergens was assessed by testing MON 87705 soybean with serum from soybean allergic individuals. The results showed that the genetic modifications in MON 87705 soybean did not increase the level of endogenous allergens when compared to conventional soybeans. In addition, compositional analysis of MON 87705 soybeans demonstrated that the antinutrient content was comparable to that of conventional soybeans.

Conclusion

Health Canada's review of the information presented in support of the food use of Improved Fatty Acid Profile Soybean MON 87705 does not raise concerns related to food safety. Health Canada is of the opinion that food derived from MON 87705 soybean is as safe and nutritious as food from current commercial soybean varieties.

Health Canada's opinion deals only with the food use of Improved Fatty Acid Profile Soybean MON 87705. 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 Improved Fatty Acid Profile Soybean MON 87705 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.

(Également disponible en français)

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