Novel food information - Herbicide Tolerant Sunflower Hybrid H4

Health Canada has notified BASF Canada Inc. that it has no objection to the sale of food derived fromHerbicide Tolerant Sunflower Hybrid H4. The Department conducted a comprehensive assessment of this sunflower hybrid 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 BASF Canada and the evaluation by Heath Canada and contains no confidential business information.

1. Introduction

BASF Canada developed Herbicide Tolerant Sunflower Hybrid H4 through chemical mutagenesis of seed and traditional breeding. Exposure to the chemical mutagen resulted in two single point mutations in the Als1 gene. This results in an alteration to the acetohydroxyacid synthase (AHAS) protein produced by Als1. The alteration in the AHAS protein permits this sunflower variety to grow in the presence of imidazolinone herbicides.

Health Canada has previously indicated no objection to the sale of imidazolinone tolerant corn (XI-12), canola (NS738, NS1471, and NS1473), rice (CL121, CL141, CFX51, and PWC16),

lentils (RH44), sunflower (X81359) and wheat (AP602CL, AP205CL, Teal11A, BW 255-2 and BW238-3) in the Canadian marketplace.

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 reflects international guidance documents in this area (e.g., Codex Alimentarius). The assessment considered: how Herbicide tolerant Sunflower Hybrid H4 was developed; how the composition and nutritional quality compares to traditional sunflower varieties; and the potential for the presence of any toxicants, anti-nutrients, or allergens. BASF has provided data which demonstrates that Herbicide tolerant Sunflower Hybrid H4 is as safe and nutritious as the conventional sunflower varieties sold in Canada.

The Food Directorate has a legislated responsibility for pre-market assessment of novel foods and novel food ingredients as detailed in Division 28 of Part B of the Food and Drug Regulations (Novel Foods). Foods derived from Herbicide Tolerant Sunflower Hybrid H4 are considered novel foods 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

Imidazolinone tolerant sunflower H4 was developed through conventional breeding of two separately mutagenized varieties of sunflower (CLHA-PLUS and IMISUN X81359).

IMISUN X81359 sunflower was derived through traditional plant breeding. This variety previously underwent assessment as a novel food, feed and plant with novel trait (NF-108). Approval from Health Canada was given in 2005 for the use of this variety in food products and for the further breeding of the variety. In X81359 herbicide tolerance is also conferred by the presence of a mutation in the Als1 gene.

CLHA-PLUS was developed using seed mutagenesis using the mutagen ethyl methansulfonate from the sunflower variety BTK47. These seeds were grown as the M1 generation to produce M2 generation seeds. The M2 generation and each subsequent generation until M5 were screened using imazapyr for herbicide tolerance. This process has been described by the petitioner and is similar to those used in previously approved Clearfield products. In CLHA-PLUS, the mutation that causes herbicide tolerance is contained in the Als1 gene. This mutation is similar to those mutations seen in previously approved Als 1 bread wheat variety (BW7) and rice varieties IMINTA 1 and 4.

Subsequently, BASF used traditional breeding to develop the H4 variety from both CLHA-PLUS and X81359. The resultant Clearfield Sunflower H4 from the breeding of these two lines contains both mutations. These mutations have successfully been bred into the H4 variety, currently at the M10 generation.

3. Characterization of the Modified Plant

The results of sequencing studies performed on cloned Als sequences from mutant plants, confirmed the presence of both the point mutations in Als1, and confirmed that no other point mutations were present in the Als1 gene. Additionally, this study confirmed that the sequences for Als2 and Als3 in H4 sunflower were identical to the wildtype. This indicates that herbicide tolerance is conferred simply by the presence of the mutations in the Als1 gene.

The petitioner has provided segregation data from three generations of crossing the H4 line with an herbicide susceptible line. Seeds from this cross were grown and subjected to herbicide treatment to test for susceptibility. From this study, the petitioner provided data which demonstrates that the trait segregates in the expected Mendelian ratio based on phenotypic results. This data indicates that this trait is inherited in a Mendelian fashion and has been stably integrated into the plant genome.

4. Product Information

The target of the imidazolinone class of herbicides is the enzyme AHAS which is responsible for the first step in the biosynthesis of essential branched chain amino acids. The mutations in both CLHA-PLUS and X81359 result in the tolerance to imidazolinone herbicides, by altering the binding site for the herbicide on the AHAS enzyme expressed by the Als1 gene, while having no effect on the normal functioning of the enzyme.

The petitioner has provided data to indicate that the AHAS enzyme produced in sunflower H4 is no different than that produced in conventional varieties, other than its tolerance of imidazolinone herbicides. The enzyme was shown to have similar activity in the presence of the branch chain amino acids valine and leucine, which have a negative feedback effect on AHAS.

5. Dietary Exposure

Herbicide tolerant Sunflower Hybrid H4 is expected to be used in similar application as traditional sunflower varieties by the food industry, namely for sunflower oil and confectionary purposes. The food use of confectionary or non-oil sunflower seed is primarily for baking, raw shelled seed consumption and direct whole seed snack consumption.

6. Nutrition

A randomized complete block design trial was conducted using CL sunflower H4, parental conventional control hybrid H7 and two conventional sunflower comparators, grown at three field sites in the United States in 2007. The petitioner indicated that the field sites and cultivation practices used in the trials are representative of environmental condition and agronomic practices used in the sunflower producing regions of Canada. Analysis of variance was used for statistical analysis of the data and a comparison of means was conducted using the LSD-test at a 95% confidence interval.

Comparisons of various nutrients and anti-nutrients were made between CL sunflower hybrid H4 and the conventional parental hybrid H7, as well as two other conventional sunflower hybrids. Compositional data from CL sunflower hybrid H4 was also compared to grain composition data from 12 other conventional sunflower hybrids.

Grain samples were analysed for proximates (moisture, protein, crude fat, crude fibre and ash), fibre composition (total dietary fibre, acid detergent fibre and neutral detergent fibre), amino acids (amino acid content, branched chain amino acids and additional essential amino acids), 33 fatty acids, 9 minerals, 8 vitamins and the anti-nutrients, phytic acid and trypsin inhibitor.

No statistically significant differences in nutrient levels were found between H4 and the parental variety, except in levels of stearic acid, and vitamin E. In all cases, components were within their respective range of values for grain from conventional sunflower cultivars.

The results of the compositional analyses collectively demonstrate that grain from CL sunflower hybrid H4 is equivalent in composition to, and as nutritious as, grain from the parental sunflower hybrid H7, as well as other conventional sunflower varieties.

7. Toxicology

The weight of evidence suggests that the mutant AHAS from Herbicide tolerant Sunflower Hybrid H4 is unlikely to demonstrate toxic or allergenic properties under usual conditions of consumption. This conclusion is based on the observations that the protein is expressed in extremely low amounts in the edible part of the sunflower, its activity is heat-labile and would be denatured during normal food preparation processes, and the protein is as sensitive to degradation in a simulated human gastrointestinal tract by trypsin as the native protein. Consequently, systemic exposure to the active AHAS protein was considered negligible. In addition, it does not share characteristics of a food allergen to a greater extent than the native protein.

In addition, the petitioner conducted an analysis of the sequence homology between a 15 amino acid sequence containing 6 amino acids before, and 8 amino acids after, each of the mutations in Als1 from two protein databases (GeneBank and Allergenonline). No homologous sequences were identified with any known allergen.

It was also noted that both the mutations have previously been introduced into other food sources for the purpose of imidazolinone tolerance. One mutation was previously introduced into Clearfield Bread Wheat BW7 and Clearfield Rice varieties IMINTA 1 and IMINTA 4. The second mutation was previously introduced in Clearfield Sunflower X81359 and in Clearfield Lentils. All these food sources have been assessed by Health Canada and been issued letters of no objection.

Conclusion

Health Canada's review of the information presented in support of the food use of Herbicide Tolerant Sunflower Hybrid H4 concluded that derived food products do not raise concerns related to safety. Health Canada is of the opinion that Herbicide Tolerant Sunflower Hybrid H4 is similar to regular conventional sunflower hybrids in terms of being an acceptable food source.

Health Canada's opinion deals only with the human food use of Herbicide Tolerant Sunflower Hybrid H4. Issues related to the environmental safety of Herbicide Tolerant Sunflower Hybrid H4 in Canada and its use as livestock feed have been addressed separately through existing regulatory processes in the Canadian Food Inspection Agency.

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