Novel Food Information - Cotton Event T304-40

Health Canada has notified Bayer CropScience that it has no objection to the food use of herbicide tolerant and lepidopteran pest resistant cotton event T304-40. 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 Bayer CropScience and the evaluation by Heath Canada and contains no confidential business information.

1. Introduction

Bayer CropScience has developed cotton event T304-40 to be tolerant to glufosinate ammonium herbicides and resistant to lepidopteran pests. Recombinant DNA techniques were used to confer tolerance to the herbicide and impart pest resistance.

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 T304-40 was developed; how the composition and nutritional quality of T304-40 compared to non-modified varieties; and the potential for T304-40 to be toxic or cause allergic reactions. Bayer CropScience has provided data that demonstrates that T304-40 cotton is as safe and of the same nutritional quality as traditional cotton 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 herbicide tolerant and pest resistant T304-40 cotton 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

• (i) 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 cotton event T304-40 and the molecular biology data that characterize the genetic change which confers resistance to lepidopteran pests and provides herbicide tolerance.

Cotton event T304-40 was genetically modified using Agrobacterium-mediated transformation of a cotton variety Coker 315 with the vector pTDL008. The transforming plasmid contains the coding sequence for the Cry1Ab protein and the PAT protein. The cry1Ab sequence is derived from the Berliner 1715 serotype of the common soil bacterium Bacillus thuringiensis (Bt). The bar gene sequence, which codes for the PAT protein, is derived from a naturally occurring soil bacterium Streptomyces hygroscopicus.

3. Characterization of the Modified Plant

Southern blot analysis and DNA sequencing of cotton event T304-40 demonstrated the presence of a single copy of the T-DNA flanked by an inverted incomplete copy of the cry1Ab gene cassette and one additional 3'me1 terminator. Further analysis showed that the translation of the rearranged sequences is highly unlikely to occur. The T-DNA inserted at a single site and at a single locus of the cotton genome. Southern blot analysis confirmed the absence of any plasmid backbone DNA in cotton event T304-40. 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 four different generations. The results of Southern blot analysis and segregation data demonstrated the stability of cotton event T304-40 at the genomic level as well as the segregation of the trait according to Mendelian inheritance principles.

4. Product Information

Cotton event T304-40 differs from conventional cotton by the insertion of two genes; cry1Ab and bar and their associated regulatory elements. The lepidopteran pest resistance in cotton event T304-40 results from the expression of the recombinant protein Cry1Ab and the glufosinate ammonium herbicide tolerance results from the expression of the PAT protein.

5. Dietary Exposure

The genetic modification of cotton event T304-40 is not intended to alter any of its nutritional aspects. It is expected that cottonseed oil from cotton event T304-40 will be used in products which are already made with cottonseed oil and thus will not result in an increase in cottonseed oil consumption. Cottonseed oil is used in cooking oil, shortening, salad dressing, and as an ingredient in crackers, cookies, and chips.

6. Nutrition

The nutrient data was obtained from test (T304-40) and control (Coker 315) cotton varieties grown at eight USA locations in a randomized complete block design with a total of nine samples of fuzzy seeds from each trial were analyzed.

Nutrients, anti-nutrients and secondary metabolites were analyzed as follows: 7 proximates (moisture, fat, protein, ash, total carbohydrate, acid detergent fibre (ADF), neutral detergent fibre (NDF)), 6 minerals (calcium, phosphorous, potassium, magnesium, iron, and zinc), one vitamin (vitamin E/alpha tocopherol), 18 amino acids (alanine, arginine, aspartic acid, cysteine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine, tyrosine), 10 fatty acids (myristic, palmitic, stearic, arachidic, behenic, lignoceric, palmitoleic, oleic, linoleic, alpha linolenic), and 6 anti-nutritional factors (free gossypol, total gossypol, phytic acid, malvalic acid, sterculic acid, dihydrosterculic acid).

There were a few statistically significant differences between event T304-40 and the control noted, but these differences were very small and analyte levels were within the published literature range for the respective analyte.

All field trial experiments used to test cotton event T304-40 were acceptable. All analyses of test, control and reference varieties were done using approved scientific and appropriate statistical methods.

The nutrient composition of cotton event T304-40 has been shown to be similar to conventional, commercial cotton.

7. Chemistry/Toxicology

The source of the cry1Ab gene is the common soil bacterium Bacillus thuringiensis (Bt) which is widely distributed in the natural environment and therefore humans have a long history of exposure to this bacterium. Also, Bt-based pesticides containing Cry1Ab have been used for decades. In addition, genetically modified corn crops containing this protein have been produced for 10 years with no adverse effects associated with consumption. Therefore, the Cry1Ab protein and its source organism can be considered to have a history of safe use. Furthermore, no Bt strain has been associated with human pathogenicity.

Acute oral toxicity studies for the Cry1Ab protein showed no adverse effects. Also, the protein is rapidly and completely degraded by simulated gastric fluid and partially degraded by simulated intestinal fluid, indicating that it would be highly unlikely to survive passage through the human gastrointestinal tract. Also, Cry1Ab does not have sequence homology to any known toxins. Therefore, exposure to the Cry1Ab proteins through the consumption of T304-40 cotton is not of toxicological concern.

The source organism for the bar gene encoding the PAT protein, Streptomyces hygroscopicus, is widely distributed in the environment. Glufosinate tolerant plants expressing the PAT protein have been grown widely in the US and Canada for over a decade with no reports of adverse effects on human food or animal feed. The PAT protein has been approved for human and animal consumption by numerous countries, and a consensus document on the genes and their respective enzymes has been publisehed by OECD (1999). Therefore, exposure to the PAT protein through the consumption of cotton event T304-40 is not of toxicological concern.

There were no signigicant differences in the levels of total and free gossypol or any other anti-nutritents (such as phytic acid, malvanic acid, sterculic acid) between T304-40 and non-transgenic varieties of cotton.

The Cry1Ab protein was shown to be unlikely to survive passage through the gastrointestinal tract and partially degraded by heat treatment, with no amino acid sequence similarity to known allergens. Also, the protein is not glycosylated in planta. It is improbable that the Cry1Ab protein would behave as as allergen in the human system. Endogenous allergens are generally not considered a concern in cotton and no allergens are included among the parameters to be analysed in cottonseed matrices for human food (OECD, 2004)

The PAT protein was shown to be readily digested in both simulated gastric and intestinal fluids. It is not degraded by heat, but all enzymatic activity is lost after incubation for 10 minutes at 50oC or higher, and has no amino acid sequence homology with known allergens.

Food products derived from cotton event T304-40 would not be associated with any greater toxicological or allergenic risk to consumer health than food products derived from conventional cotton currently available in the Canadian market.

Conclusion:

Health Canada's review of the information presented in support of the food use of herbicide tolerant and pest resistant cotton event T304-40 does not raise concerns related to food safety. Health Canada is of the opinion that food derived from cotton event T304-40 is as safe and nutritious as food from current commercial cotton varieties.

Health Canada's opinion deals only with the food use of cotton event T304-40. 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 cotton event T304-40 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.

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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