Genetically Modified Foods An Overview of the Safety and Labeling Requirements in Canada

Introduction

The topic of genetically modified (GM) organisms has been a hot topic of discussion for the past few decades as the general population had become more aware of them. There is also an ever growing concern with the safety of the foods that we consume. This concern is exacerbated further with the introduction of GM foods. Technology in molecular biology, with genetic manipulation has progressed extensively within the last 50 years and is applied to the foods that we consume. Government agencies around the world have set standards to protect their citizen from any potential hazards that may arise from GM foods. Before delving into the regulatory standards that are set in place to ensure the safety of a GM food, it is important to understand the technology of how these GM foods are engineered. This paper will not discuss the intricate details of specific genetic engineering techniques that are available, but rather a generalized understanding from a gene of interest to a final product (plant/crop). Every living cell has a set of instructions inside them to control factors such as growth and development, these are known as genes. These genes are found in the chemical structure known as deoxyribonucleic acid (DNA). Genes are the instructions that make it possible for cells to functions by making proteins and enzymes. Certain proteins and enzyme has specialized functions in specific organisms such as the Bt gene found in Baillus thuringiensis, which produces a toxin that is deadly to larvae of pest insects. The process of genetic engineering can start with this specific gene as an example, and then inserting that gene into a plant to confer the same resistance against those pest insects. The process starts with a gene of

interest, which needs to be isolated and then transferred to the plant host. The transfer can be performed with various methods of transfection (transformation) which can include electroporation, liposomes, and bacterial vectors (Agrobacterium), to name a few. The plant cells that took up the gene of interest would then be selected for and grown into a complete plant. The plants would then be breed to determine whether the gene had transferred to the subsequent generations.

Benefits and Risks The prevalence of the GM foods has increased in the last 20 years and is ever growing. The first GM food that was introduced to the market place was the Flavr Savr tomato. In Canada alone there are over 80 GM crops/foods that have been approved for sale. These foods can be further processed into other food products, which in most cases would be considered genetically modified. In 2011, 29 countries have adopted GM crops and the total global area that is covered by GM crops was 160 million hectares. Soybean is the world most cultivated transgenic plant (occupying 75.4 million hectares or 47% of global biotech area), followed by corn (51.00 million hectares at 32%), cotton (24.7 million hectares at 15%), and then canola (8.2 million hectares at 5%).(1) Canada was ranked 5th in the world, with a growing area of 10.4 million hectares and the main cultivated transgenic plant are canola, maize, soybean, and sugarbeets. (1) With such a prevalence of GM foods, the benefits and risks of these foods have been discussed at great lengths. Advantages of developing GM foods can have almost infinite possibilities. As the functions for novel and existing genes are elucidated their application to GM food will further increase. With the substantial knowledge already existing in the functions of genes, it is not

surprising that there is already a large list of benefits that are already applied to GM foods. As already mentioned the first GM food to the market was the Flavr Savr tomato. This product had the advantage of being tastier, firmer and fresher compared to its comparator.(2) There has been a need for crops to mature quicker with higher yields. This has been addressed with products that range from fruits, vegetables, grains, and nuts. One major advantage with genetically manipulating crops is to confer resistance to pests (insects and weeds) and disease. Throughout history this has been a major problem that has led to large famines and great emigration. One particular example is the great potato famine in Ireland at the end of the 19th century. This was caused by potato blight, a fungal infection (Phytophthorainfestans), which caused mass starvation, with the deaths of approximately one million people and causing another million people to emigrate.(3) Roundup was developed by Monsanto as an herbicide but the chemical also had problems with the crop themselves. They were able to get around this by developing crops that would be resistant to the herbicide, and Monsanto has developed several products out on the market that are specifically tailored to confer resistance to Roundup.(4) Monsantos MON810 GMO maize is an example of a crop that has been created to work as an insecticide. More specifically MON810 using the Bt gene to confer this resistance.(5) Lastly genetic modifications can alter and help improve the nutritional profile of a food. Scientists are able to design foods to meet specific nutritional goals through genetic engineering and a particular example of this is Golden Rice. Golden Rice was designed to help children who suffer from vitamin A deficiency in poor countries. The psy gene from daffodil and crtI gene from the soil bacterium, Erwinia uredovora were transformed into rice grain as two beta-carotene biosynthesis genes to biosynthesize beta-carotene (pro-vitamin A) in the edible parts of rice.(6) With this quick overview of some of the advantages and benefits that already exist, it is easy to observe the large

potential of GM foods in the near future. With the flood of GM foods and crops appearing on the market, there is a growing concern from the public and regulatory organizations about the associated risk from the consumption of these types of products. There have been many studies conducted by the scientific community with the risks associated with GM foods. Some of these worries stem from the development of allergies relating to GM foods. One study identified protein expression in certain transgenic food crops had short spans of amino acid sequences that were identical to IgEbinding linear epitopes that are responsible to induce an allegoric responses.(7) Another concern from these studies is the introduction of new toxins from GM foods. This can be seen in various animal studies, where lab animals would be fed GM foods and toxicity levels in the bodies can be detected after consumption. One study observed hepatorenal toxicity when fed GM food MON863, although the study may not be conclusive enough to determine whether MON863 is a safe product, there still is the potential risk.(8) Lastly is the effect these GM foods have to the general population indirectly by unforeseen environmental hazards. These environment hazards can include the unintentional harm to other organisms. This can be seen in the study by Losey et al., where it has been reported that there was a steep decline in monarch butterflies populations in the areas where a specific GM crop was planted. This GM food had detrimental consequences for the larvae that ingested it.(9) Another environmental hazard is the unintentional spread of genetic material to other crops and plants. This could be a serious problems especially for crops at would be certified organic. For these crop growers there would be almost no way of insuring that their crops have been genetically altered. This could also have unforeseen effects where insecticide resistance genes could be spread into areas where an insect eco-system could be at risk. Studies on the GM foods/crops are constantly on-going and assessed with the advancement

of new technology relating to the industry. Regulatory groups must also stay current with studies conducted by institutions along with their own standards to determine whether new products in the market are safe for the public.

Safety Assessment of Genetically Modified Foods

In Canada the review process for safety is determined by two regulatory bodies, Health Canada and the Canadian Food Inspection Agency (CFIA). Health Canada is responsible for establishing the regulatory standards and policies that ensure the safety and nutritional quality of all food and novel foods, sold for the Canadian marketplace. A novel food is defined by Health Canada in two parts, the first part being as a substance, including microorganisms, that does not have a history of safe use a food. The definition also includes that if the preparation, preservation or packaging changes and if these changes have not been that has previously been applied to that food or if the food undergoes a major change, it would be considered a novel food. The second part of the definition of novel foods includes, genetically modified foods that are derived from plants, animals or microorganisms such that: the plant, animal or microorganism exhibits characteristics that were not previously or no longer exhibits characteristics that were previously observed in that plant, animal or microorganism.(10) The CFIA on the other hand is the branch that handles the inspections and enforces these standards and policies set forth by Health Canada. The other areas the CFIA is involved in are developing standards that relate to the packaging, labeling and the advertisement of foods. The CFIA also handles a wide variety of other duties not discussed in this paper, which includes responsibilities in areas of: regulation of seeds, veterinary biologics, fertilizers and livestock feeds.(11)

Within Health Canada, the Health Products and Food Branch (HPFB) is the branch that is responsible for the regulations of novel foods. This branch encompasses a wide range of directorates; more specifically, it is the Food Directorate (FD) that is ultimately responsible for laying down the regulatory standards and policies to ensure safety.(12) Health Canada started regulating the sales of novel in 1999. This process involves a mandatory pre-market notification process as the safety assessment. The pre-market notification process involves the submission of information by the manufacturer or importer of a novel and the determination can be deemed acceptable or not prior to the sale of the food product. (10) This safety assessment by Health Canada was modeled after international expert organizations include: the World Health Organization (WHO), the Food and Agriculture Organization (FAO), the Codex Alimentarius Commission, and the Organization for Economic Co-operation and Development (OECD).(11) In general the safety assessment by Health Canada involves how the novel food was developed. This modified food is then compared to a non-modified counterpart. This counterpart food is used as a comparator because of its history of safety for consumption. The nutritional information of the modified food must also be compared to its comparator. As mentioned earlier with the growing concern about GM foods, the potential introduction of new toxins, allergic reactants must be assessed as well. This stringent evaluation process is outlines in the Food and Drug Regulations (under part B, division 28) and the guidelines for the safety assessment of novel foods (2006). To summarize the Food and Drug Regulations (B.28.002), the manufacturer or importer must notify the director before the intention to sell or advertise the novel food. To notify the director, the manufacturer or importer must submit the mandatory pre-market notification. Once the pre-market information package is received, a review process will start to assess the safety of the novel food. During the evaluation the reviewers will thoroughly review

all data and protocols outlined by the manufacturer or importer on the novel food. If there is anything that is unclear to the reviewers, the directory will notify the manufacturer or importer for clarification and make a request for additional information. Once the data package is deemed satisfactory then a letter of no objection from the director will be sent out which permits the manufacturer or importer to sell and/or advertise the novel food product. The results of this decision process will be published on Health Canadas website. A systematic of the review and decision process is outline on Figure 1 in the appendix. The pre-market notification package is outlined in the guidance document, guidelines for the safety assessment of novel foods (2006). This document specifies the type of data is required from Health Canada to assess the safety of a novel food. The document tries to encompass the wide range of various types of foods and because of this there are sections of the document that may not apply to all types of foods that are being submitted for the review process. As mentioned in the document, with any type of experiments that are required to generate data to show safety should be done in a scientific manner with sound concepts, principles and good laboratory practices (GLP). The type of data that is required in the pre-market notification package is divided into 3 sections which include: foods derived from plants, foods derived from microorganisms and foods derived from animals (this section is still under development). Within each section there are 3 subsections: substance with no history of safe use, novel process, and genetic modification. The subsection of substance with no history of safe use is where the manufacturer or importer must describe the history of use, any information on dietary exposure (if any), and nutritional, toxicology, allergenicity, chemical considerations. Under the Novel process subsection details must be provided about the novel process of the food, again information on dietary exposure (if any), history of organism, and nutritional, toxicology,

allergencity, chemical considerations. Lastly the subsection that describes the genetic modifications requires data in the topics of characterization of the derived line, genetic modification considerations, history of organism (host and donor(s)), dietary exposure, and nutritional, toxicology, allergencity, chemical considerations. The process of the pre-market notification is an arduous task which ensures the safety of GM foods that are introduced in the Canadian market place for consumption.(13-15)

Labeling Genetically Modified Foods

Labeling is intended to provide consumers with consistent information and give consumers the freedom to make informed food choices. Health Canada and the CFIA take joint responsibility for federal food labeling policies under the Food and Drugs Act.(16) The CFIA standards maintains that the food labels are truthful and not misleading to the consumers. The labeling standard for GM food, Voluntary Labeling and Advertising of Foods that are and are not Products of Genetic Engineering , as a National Standard of Canada was published in 2004. This standard provides criteria for making voluntary labeling and advertising claims of GM foods.(17) According to this standard, both voluntary positive (does contain GM) and voluntary negative (does not contain GM) labeling are permitted and it applies to all kinds of foods, including pre-packaged, bulk, and food prepared at the point of sale. (17) The specific examples of acceptable and non-acceptable labeling statements in the standard make it a comprehensive guidance for food companies, manufacturers and importers. The labeling of genetically modified foods is a big and controversial topic. There is a lack of harmonization of the regulations on GM food labeling around the world. Some countries

adopt a mandatory labeling policy, like the European Union, Australia and Japan, while others are just planning to introduce the GM labeling regulations, such as countries like Singapore and Egypt.(18) In Regards to the extensive North America market of GM foods, U.S and Canada both agree that voluntary labeling is the best option at the current stage. We can see a growing number of countries adopted labeling policies for GM food in the international community. (18) However, the intense debate surrounding the mandatory labeling of GM food is still ongoing. Any discussion about labeling of GM foods would inevitably involve the proposal of a right to know list of GM ingredients in their food. Staunch supporters of mandatory labeling would insist that the consumers know the ingredients of their food, especially for those consumers who are in high doubt about the safety of GM food products. Religious and ethical perspectives should also be taken into consideration. In many societies, people want to avoid consuming animal products.(19) That means these people might refuse to consume foods with genes that are from an animal source. For those people who have different attitudes towards mandatory labeling, they think mandatory labeling will increase the cost of the products, and it would be unfair to impose the extra expense on the consumers who are indifferent about the situation. This would especially affect individuals and families with low income. Additionally, they believe that consumers can purchase certified organic foods to avoid GM foods as an alternative option and mandatory labeling would be pointless because there are no guarantee conventional crops are free of their GM counterparts.(20)

Discussion

From a regulatory perspective, there are stringent guidelines that companies have to follow in order to market GM foods. This can be seen with the pre-market notification process set forth by the Food Directorate (FD) of Health Canada and the CFIA. The pre-market notification process determines the safety of GM products by investigating the various aspects of the GM food in question. While the guidance documents address the majority of safety aspects of novel foods, they do not include some important topics that should be under review as well. Firstly, the impact of GM products on the environment is not properly discussed. This aspect of GM products is a big concern and should be address immediately, as future implications to the environment are not fully understood and some safety measures should be place to prevent any complications. While this section of the guidance is still under development by Health Canada, by the time it takes to publish a draft document on the matter, potential problems may already arise. The second problem with the safety assessment of GM foods is that Health Canada does not address the novel foods that are derived from animals. Health Canada does understand that this is a concern but has not yet implemented clear guidelines to address products that are genetically modified from animal origins. In terms of the safety assessment submissions to Health Canada, these are some of the major deficiency Health Canada needs to concentrate on to ensure the safety of novel foods. We believe the voluntary labeling of GM food is more efficient for the Canadian food market, especially since all the GM foods are stringently evaluated and safety is approved by Health Canada. According to Health Canadas database, there are no GM foods that contain animal DNA on the Canadian market place, and in this case, the uncertainties of religious and ethical concerns are eliminated. On the other hand, food companies will keep the price premium between labeling and non-labeling products as low as possible to maintain better market share if

the labeling policy is only voluntary which would be beneficial to all the consumers. With the advancement of technology, the adaptation into food products was inevitable. Whether people are against the use of genetically modified foods, it has become a large aspect of peoples lives. While there could be negative impacts on the population as well as the environment, there are considerable advantages and future implications for GM foods. The advantages at this stage in the development of GM foods certainly outweigh the negatives. This can be seen in crops that confer resistance to drought and disease for countries that would not be able to grow crops otherwise. With further refinement of the technology behind GM foods, the disadvantages we face today can be overcome. The negative impacts should be taken into serious consideration but should not deter us from perusing further innovations in the field. If the same unconstructive approach was seen by the medically community a hundred years ago, we would not have the same advancements that treat and prolong the lives of billions of people today. The population of the world is ever growing and sustainability will become an issue in the near future. It is important to note that advancements in technology throughout civilizations have led us to increasing the capacity of the world population with the finite resources that surrounds us.

References (1) James C. (2011). Global Status of Commercialized Biotech/GM Crops: ISAAA Briefs, Brief 43-2011. Retrieved from http://www.isaaa.org/resources/publications/briefs/43/executivesummary/default.asp. (2) Martineau, B. (2001). First Fruit: The creation of the Flavr Savr tomato and the birth of biotech food. McGraw-Hill. (3) Donnelly, J. (2011). The Irish famine, BBC History. Retrieved from http://www.bbc.co.uk/history/british/victorians/famine_01.shtml. (4) Monsanto. Crop specific recommendations. Retrieved from http://www.monsanto.com/weedmanagement/Pages/crop-specific-recommendations.aspx. (5) Spiroux de Vendomois, J., Roullier, F., Cellier, D., Seralini, G. (2009). A comparison of the effects of three GM corn varieties on mammalian health. Int J Biol Sci. 5(7): 706-726. (6) Ye, X; Al-Babili, S; Klti, A; Zhang, J; Lucca, P; Beyer, P; Potrykus, I. (2000). Engineering the provitamin A (beta-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm. Science. 287(5451): 303305. (7) Kleter, G.A. and Peijnenburg, A.A.C.M. (2002). Screening of transgenic proteins expressed in transgenic food crops for the presence of short amino acid sequences identical to potential, IgE-binding linear epitopes of allergens. BMC Struct. Biol. 2, 819. (8) Seralini, G., Cellier, D., and Spiroux de Vendomois, J. (2007) New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity. J. archives of Env. Contam. and Toxicology. 2, 596-602. (9) Losey, J.E., Rayor, L.S. and Carter, M.E. (1999). Transgenic pollen harms monarch larvae. Nature.399, 214. (10) Canadian Food Inspection Agency. What is considered a novel food product in Canada? Retrieved from http://www.inspection.gc.ca/english/fssa/fispoi/product/novbroche.shtml. (11) Health Canada. Food and Nutrition Factsheets & Frequently Asked Questions: Biotechnology and Genetically Modified Foods. Retrieved from http://www.hc-sc.gc.ca/fnan/gmf-agm/fs-if/index-eng.php. (12) Health Canada. About Health Canada - Branches and Agencies. Retrieved from http://www.hc-sc.gc.ca/ahc-asc/branch-dirgen/index-eng.php. (13) Department of Justice Canada. (2012). Food and Drugs Act. Retrieved from http://lawslois.justice.gc.ca/.

(14) Department of Justice Canada. (2012). Food and Drug Regulations. Retrieved from http://laws-lois.justice.gc.ca/. (15) Health Canada. (2006). Guidelines for the Safety Assessment of Novel Foods. Retrieved from http://www.hc-sc.gc.ca/fn-an/legislation/guide-ld/nf-an/guidelines-lignesdirectriceseng.php. (16) Canadian Food Inspection Agency. Labeling of Genetically Engineered Foods in Canada Retrieved from http://www.inspection.gc.ca/food/labelling/other-requirements/method-ofproduction/ge-factsheet/eng/1333373177199/1333373638071. (17) Public Works and Government Services Canada. Voluntary Labeling and Advertising of Foods that are and are not Products of Genetic Engineering. Retrieved from http://www.tpsgcpwgsc.gc.ca/ongc-cgsb/programme-program/normes-standards/internet/032-0315/indexeng.html. (18) Gruere, G.P., and Rao, S.R. (2007). A review of international labeling policies of genetically modified food to evaluate Indias propose rule. AgBioForum, vol. 10, no. 1, Retreieved from www.agbioforum.org. (19) Pat Byrne. Labeling of Genetically Engineered Foods. Retrieved from http://www.etseq.urv.es/doctorat/index/running/2003_2005/courses_w/web_nanobiotech/handou ts/Handout%2010%20GM%20Food%20Labelling.pdf. (20) Canadian Broadcasting Channel. Genetically Modified Food: A Growing Debate. Retrieved from http://rc-archives.cbc.ca/lifestyle/food/topics/1597/.

Appendix

Figure 1. Process of assessing safety of a GM food through the FD of Health Canada. (15)