foods derived from genetically modiﬁ ed crops: issues for ... · foods derived from genetically...

Foods Derived from Genetically Modifi ed Crops:

Issues for Consumers, Regulators and Scientists

For more information about the South Asia Biosafety Progam or about this publication, please contact:

AGBIOS Inc.106 St. John Street, P.O. Box 475

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Tel: +1 613 269 7966; Fax: +1 613 269 4367E-mail: [email protected]: www.agbios.com

Copyright © 2005 AGBIOS. All rights reserved.

Table of Contents ................................................................................3

Conference Agenda .............................................................................5

Abstracts & Biographies ....................................................................7

Background Note: The Regulation of Genetically Modifi ed

Organisms in India ...........................................................................57

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

GOVERNMENT RULES FOR GMOs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

FOOD CONTROL SYSTEM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

THE FOOD SAFETY AND STANDARDS BILL, 2005 . . . . . . . . . . . . . . . . . . . . 64

OVERVIEW OF MINISTRIES AND DEPARTMENTS INVOLVED IN REGULATION OF GM FOOD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

STATUS OF DEVELOPMENT OF GM FOOD CROPS IN INDIA . . . . . . . . . . . 67

LABELLING ISSUES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Codex Alimentarius Principles for the Risk Analysis of Foods

Derived from Modern Biotechnology ..............................................69

Codex Alimentarius Guideline for the Conduct of Food Safety

Assessment of Foods Derived from Recombinant DNA Plants ....73

Table of Contents

Conference Agenda

Day 1: September 26, 2005

Time Presentation Speaker

0900 Registration

0930 Inaugural/Opening Session Welcome: Dr. Vasantha Muthuswamy, Senior DDG, Indian Council of Medical Research Address: Dr. Morven A. McLean, President, AGBIOS Inc. Address: Dr. S.R. Nair, Managing Director, Biotech Consortium India Limited Address: Ms. Rita Teaotia, Joint Secretary, Ministry of Health and Family Welfare Address: Shri A.N.P. Sinha, Joint Secretary, Ministry of Food Processing Industries Inaugural Address: Dr. M.K. Bhan, Secretary, Department of Biotechnology Vote of Thanks: Dr. G.S. Toteja, Deputy Director General, Indian Council of Medical Research

1000 Tea

Technical Session I: The Regulation of GM Foods

Chairpersons:

Shri A.N.P. Sinha, Joint Secretary, Ministry of Food Processing Industries Ms. Rita Teaotia, Joint Secretary, Ministry of Health & Family Welfare

1030 Regulating GM Foods: A Global Snapshot Dr. M.A. McLean, AGBIOS, Canada

1100 Regulating GM Foods in India Dr. T.V. Ramanaiah, Director, DBT

Dr. S.R. Gupta, Joint DCGI, MoH

1200 Discussion and Q&A

1300 Lunch

Technical Session II: Key Elements in the Safety Assessment of GM Foods

Chairpersons:Dr. B. Sivakumar, Director, National Institute of Nutrition Dr. K.K. Tripathi, Advisor, Department of Biotechnology

1400 The Work of the Codex ad hoc Intergovernmental Task Force on Foods Derived from Biotechnology

Mr. Patrick Deboyser, Minister-Counsellor (Health & Food Safety), EC

Dr. D. Chattopadhya, Shadow Committee on GM Foods of National Codex Committee of India, MoH and ADG (PFA), DGHS, MoH

1500 Assessing the Potential Allergenicity of Foods Derived from GM Crop Plants

Dr. R. Goodman, University of Nebraska - Lincoln, USA

Dr. Naveen Arora, Institute of Genomics and Integrative Biology

1600 Tea

1615 Nutritional Assessment of Genetically Modified Foods

Dr. B. Sivakumar, Director, NIN

Dr. I. Munro, CANTOX Health Sciences International, Canada

1715 Assessing the Potential Toxicity of Genetically Modified Foods

Dr. W. Seinen, Institute of Risk Assessment Sciences, Netherlands


1830 Close of Day 1

Day 2: September 27, 2005

Time Presentation Speaker

Technical Session III: Public Participation and the Consumer

Chairpersons:Shri Chaman Kumar, Joint Secretary (CK), Department of Child and Women Development Dr. Kamla Krishnaswamy, Former Director, National Institute of Nutrition and President, National Nutrition Society of India

0930 GM Foods and Consumer Acceptance in Asia Mr. K. Keh Kok Leong, Asian Food Information Centre, Singapore

1000 Public Perception of GM Foods in India Dr. Suman Suhai, Gene Campaign

Dr. Sriram Khanna, Consumer Voice

1100 Tea

1115 Consumer Labelling and Traceability Regimes Dr. S.R. Rao, OSD to Minister of Science and Technology

Prof. C. Kameswara Rao, Executive Secretary, Foundation for Biotechnology Awareness And Education


1300 Lunch

Technical Session IV: Challenges and Opportunities

Chairpersons:Dr. P.S. Chauhan, Emeritus Scientist, Department of Biosciences, Bhabha Atomic Research StationDr. Vasantha Muthuswamy, Senior Deputy Director General, Indian Council of Medical Research

1400 Assessing the Safety of Nutritionally Enhanced Genetically Modified Foods

Dr. Vandana Shiva, Navdanya

Dr. I. Munro, CANTOX Health Sciences International, Canada

1500 Post-Commercial Monitoring of GM Foods Dr. C. Bruhn, University of California Davis, USA

1530 Tea

1545 Public Consultation in Decision Making in Australia & New Zealand

Mrs. L. Buchtmann, Food Standards Australia & New Zealand

1615 Challenges in Decision Making: the Indian Context Dr. G.S. Toteja, DDG, ICMR


1730 Close of Conference

7

Regulating GM Foods: A Global SnapshotDr. Morven A. McLean, AGBIOS Inc., Canada

Appropriately deployed, genetically engineered plants have the potential to contribute to sustainable gains in agricultural productivity. However, uncertainty about the potential for adverse human health conse-quences arising from the consumption of foods derived from genetically engineered plants in agriculture has lead to the development of regulatory regimes that are applied specifi cally to assess the safety of these products. To date, a total of 80 transgenic events have been approved for human food consumption in 17 countries. Th e food safety regulatory systems in these countries often diverge around key elements such as the legislative framework, regulatory triggers, transparency, public involvement, and approaches to risk assessment and risk management. Th is presentation will introduce how these elements are being addressed by various countries.

Dr. Morven McLean is the president of AGBIOS, a consulting fi rm dedicated to providing public policy, regu-latory and risk assessment expertise to agricultural biotechnology stakeholders in the public and private sectors. Before joining AGBIOS, she was Chief of Canada’s Plant Biosafety Offi ce, the national regulatory authority for the assessment and release of genetically modifi ed plants, where she was responsible for the development, implementation and review of regulatory programs. Dr. McLean was also the Canadian Food Inspection Agency’s (CFIA) technical expert on biotechnology and advisor to senior CFIA management and the offi ce of the Minister of Agriculture and Agri-Food Canada. Prior to this, she had a productive research career with Agriculture and Agri-Food Canada where she worked on developing virus-resistant transgenic small fruits, and in the private sector leading a program to develop diagnostic tests for the detection of commercially important plant pathogens.

Abstracts & Biographies

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Regulating GM Foods in IndiaDr. T.V. Ramanaiah, Director, Department of Biotechnology, Government of India

Dr. T.V. Ramanaiah is Scientist – (Director) in the Department of Biotechnology (DBT), Ministry of Science & Technology, Government of India. He joined DBT in 1990 after a research career at National Institute of Communicable Diseases and Malaria Research Centre, Delhi. Dr. Ramanaiah is associated with the regulation of recombinant DNA technology in India as Member-Secretary of Review Committee on Genetic Manipulation (RCGM) and Monitoring-com-Evaluation Committee (MEC). Dr. Ramanaiah is actively involved in biosafety assessment of transgenic crops, GMOs and products thereof. He played a signifi cant role in release of Bt Cotton hybrids in India and also took part in the negotiations of Cartagena Protocol on Biosafety and contributed in shaping up of AIA procedure and annexure for risk assessment.

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Regulating GM Foods in IndiaDr. S.R. Gupta, Joint DCGI, Ministry of Health, Government of India

Dr. S.R. Gupta, M.Sc. Ph.D. from Patel Chest Institute, New Delhi is Joint Drug Controller General of India in the Ministry of Health and Family Welfare, Government of India. He has been involved in the implementa-tion of the Prevention of Food Adulteration (PFA) Act in the country for several years.

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The Work of the Codex ad hoc Intergovernmental Task Force on Foods Derived from BiotechnologyMr. Patrick Deboyser, Minister-Counsellor (Health & Food Safety), Delegation of the European Commission to Th ailand

Mr. Patrick Deboyser received his law degree from the University of Louvain, and was called to the Brussels Bar in 1979. From 1980 to 1983, he was Legal Adviser to BEUC – the European Bureau of Consumers Unions. Having joined the European Commission in 1984, he became Head of ‘Pharmaceuticals’ in 1995, Head of ‘Pharmaceuticals and Cosmetics’ in 1997, and Head of ‘Food Law and Biotechnology’ in 1999. In this last capac-ity, he was responsible for the development of EU legislation on general food law, food labelling and genetically modifi ed food and feed. Since October 2004, Mr Deboyser is Minister-Counsellor in charge of Public Health and Food Safety in the Delegation of the European Commission to Th ailand. He is still a member of the EC delegation to the Codex Alimentarius Ad-Hoc Task-Force on Foods derived from Biotechnology and to the Codex Committee on Food Labelling. Th e author of several books and articles, Mr Deboyser has taught European Law at the University of Brussels (ULB) and the University of Louvain (UCL). He is currently Professor of Food Safety at the European College of Parma.

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The Work of the Codex ad hoc Intergovernmental Task Force on Foods Derived from Biotechnology: the Indian PerspectiveDr. D. Chattopadhya, Shadow Committee on GM Foods of National Codex Committee of India, MoH and ADG (PFA), DGHS, Ministry of Health and Family Welfare, Government of India

Dr. D. Chattopadhya is an MBBS, MD and a microbiologist and has been in service of the Government of India for more than 20 years. Prior to joining the Ministry of Health, he was the Joint Director at the National Institute of Communicable Disease, New Delhi, looking after the HIV AIDS Project. He is currently the ADG(PFA) in the Ministry of Health and Family Welfare and the Member Secretary, Shadow Committee on GM Foods of National Codex Committee of India.

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Assessing the Potential Allergenicity of Foods Derived from GM Crop PlantsDr. Richard E. Goodman, University of Nebraska - Lincoln, USA

Food allergy is an area of increasing public and scientifi c awareness. Public perception in the US and EU is that 20 to 30% of individuals are food-allergic. Yet current estimates of prevalence from clinical, scientifi c studies in the US and EU are that 1-2% of adults, and 6-8% of infants and young children are allergic to one or more foods. Young children usually become tolerized over time, but some individuals either fail to acquire immune tolerance or became sensitized because of genetic or environmental factors. Protein specifi c IgE-mediated allergen cross-linking on mucosal mast cells is the primary event initiating the allergic reaction that varies from mild hives, or edema to asthma or anaphylaxis in those severely aff ected.

By 1992, US regulators recognized that biotechnology might lead to the unintentional transfer of genes encoding strong allergens from one organism, into another crop. An assessment strategy has been de-veloped to evaluate, and when appropriate test any introduced protein based on comparisons to known allergens, thus reducing the potential risk. Th e greatest risks (in order): transfer of an allergen, transfer of a cross-reactive protein and to a lesser extent, transfer of a protein similar in physical-chemical parameters to common food allergens. Characteristics common to many allergenic food proteins include abundance, stability to heat and digestion by pepsin, and repeating multimeric or highly cross-linked (S-S) structures. Lists of known and putative allergenic proteins are available at www.allergenonline.com and www.aller-gome.com. Highly labile fruit and airway allergens may cause cross-reactions due to IgE specifi c binding to conformational epitopes conserved in structures of homologous proteins.

Th e allergy assessment of GM crops begins with the evaluation of the allergenicity of the source organism of the gene. If commonly allergenic, serum from donors allergic to the source are tested for IgE binding to the transferred protein. Th e sequence of all transferred proteins is compared to known allergens using FASTA (or BLAST) to identify matches of greater than 35% identity over 80 or more amino acids. Th is is one of the most predictive tools for identifying potentially cross-reactive proteins. Other comparisons, such as matches of 8 amino acids, or structural motif prediction have not yet proven predictive (Goodman et al., Int. Arch. Allergy Immunol. 2005). Proteins greater than 35% identity are screened for IgE binding with sera from individuals with proven allergies to the matched allergen. Careful selection of allergic and control donors is essential and assays must be designed and validated to reduce the rate of false positive and false negative reactions. Sometimes in vivo challenges are required to verify results. Pepsin digestibility is performed along with an assessment of protein abundance. Th e evidence is evaluated together to assess the overall potential of risk (Codex, ALINORM 03/34, 2003). Other tests such as digestibility in pancreatin, thermal stability, immunogenicity and animal model tests have not yet proven suffi ciently predictive to improve the assessment. It should be recognized that while the risks of food allergy for proteins assessed in this way is small, it will never be zero.

Dr. Goodman is a Research Professor in the Food Allergy Research and Resource Program, Dept. of Food Science and Technology, University of Nebraska-Lincoln. He received his Ph.D. in Dairy Science from Ohio State University (1990), postdoctoral training in immunology and parasitology at Cornell University (1990-1993), and worked as a Research Scientist at the University of Michigan (1993-1997). At Monsanto Company (1997-2004) he directed experiments to evaluate potential animal models of allergenicity, refi ne the pepsin digestion assay, test bioinformatics methods to assess potential cross-reactivity and develop methods for serum IgE testing of novel (GM) proteins. Dr. Goodman participated in the Codex Working Group Task Force on the Allergenicity Assessment of GM plants and in animal model and pepsin resistance studies sponsored by the International Life Science Institute. He currently directs the AllergenOnline database at the University of Nebraska. Th e focus of his experimental work is on the identifi cation of allergenic proteins and relative allergenicity of crops and food

18

fractions. He is a member of the European Academy of Allergy and Clinical Immunology and the American Academy of Asthma, Allergy and Immunology. Dr. Goodman has co-authored 25 peer reviewed scientifi c papers and book chapters and presented invited seminars on food allergy and the allergenicity assessment of genetically modifi ed crops in Korea, Taiwan, India, Egypt and the U.S.

21

Assessing the Potential Allergenicity of Foods Derived from GM Crop PlantsDr. Naveen Arora, Institute of Genomics and Integrative Biology

Food allergies are an abnormal response of the body’s immune system to specifi c protein(s) in foods and are mediated by allergen-specifi c immunoglobulin E (IgE) antibodies. About 25% of the population is aff ected by allergic disorders and this is increasing at a very high rate. Exposure to new allergens may increase the sensitivity of individuals. Foods derived from GM crops will be introduced soon in the market therefore, safety and allergenicity assessment of these GM crops is essential to protect the population. Th ere are very few studies that provide information about allergenic potential of GM crops. FAO/WHO/OECD has proposed certain guidelines for safety and allergenicity evaluation of GM crops. Potential allergenicity of the introduced proteins can be compared with the native crop by focusing on the source of the transferred genetic material, sequence homology of the introduced protein with known allergen databases, heat and processing stability, eff ect of pH and/or gastric juices (digestive stability) and also animal studies. Specifi c and targeting screening with the human sera is essential to know the allergenic potential of the protein expressed in the GM crop. Skin test of native and GM crop on food allergy patients is required to look for systemic/ untoward reaction. Th e testing with the above criteria provides reasonable assurance about allergenic potential of the GM food in question.

Naveen Arora, Ph.D. Biochemistry is a senior scientist working with IGIB, New Delhi. He has been awarded a distinguished letter for performing excellent work in the fi eld of Allergy by NIAID, NIH, MD USA. He is the recipient of Alexander von Humboldt Fellowship and was visiting associate in Bethesda. He is a fellow of Indian College of Allergy and Applied Immunology and a member of several societies.

23

Assessing Potential Toxicity of Genetically Modifi ed FoodsDr. Willem Seinen, Institute for Risk Assessment Sciences, Utrecht University, Netherlands

Th e development of genetically modifi ed (GM) crops has prompted widespread debate regarding both human safety and environmental issues. International consensus has been reached on the principles regarding evaluation of the food safety of GM plants. Th e concept of compositional equivalence has been developed as part of the evaluation framework, based on the assumption that existing foods with a history of safe use can serve as a basis for comparison of the GM food with the appropriate counterpart. Application of this concept is the cornerstone to identify similarities and diff erences between the existing food and the new product and the starting point in the toxicological safety evaluation. Th e diffi culties of traditional toxicity testing of whole foods and the risk assessment procedures are discussed along with the evaluation strategy for the new GM products to ensure the safety of these products for consumers. It is concluded that the strategy based on the concept of substantial equivalence has proven adequate in the safety assessment of GM derived food and feed.

After his DVM-graduation Willem Seinen started in experimental animal pathology at the Nutrition and Food Research Institute, a division of the Netherlands Organization for Applied Scientifi c Research (TNO), and returned to the University of Utrecht to initiate a research group on immunotoxicology. After his PhD thesis he got a chair in Biological Toxicology, started together with Wageningen University a postdocteral and vocational training program in toxicology and founded the research institute of toxicology (now the Institute of Risk Assessment Sciences) at Utrecht University and initiated close research cooperation with the National Institute for Health and Environment and TNO-Food and Nutrition. At present he is member of many scientifi c advisory boards, such as the Health Council of the Netherlands. He is also member of the GMO Panel of the European Food Safety Authority.

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Nutritional Assessment of GM FoodsDr. Ian Munro, CANTOX Health Sciences International, Canada

Available information indicates that in certain regions of the world nutrient defi ciencies in the population can be signifi cant. Crops derived from biotechnology have the potential to increase food availability and help prevent nutrient defi ciencies. From 1995 to the present there has been a very large increase in areas planted to biotechnology derived cultivars. Th e main purpose of these GM traits has been to improve agronomic traits such as herbicide-tolerance and protection against certain insect pests and reduce input costs.

Th e nutritional safety of biotechnology derived foods requires a careful evaluation of: (a) the safety of the genetic construct; (b) how the composition of the new variety compares with a suitable comparator with a history of safe use; and (c) whether unintended compositional changes have occurred that may be determined to aff ect the safety of the crop. Th e principal focus of the nutritional safety evaluation is on comparative analyses to ensure that compositional changes have not occurred that would decrease the nutritional value of the crops. As a check on nutrient value, studies may be performed in laboratory animals or livestock to substantiate nutritional safety.

Dr. Munro is an internationally recognized authority on toxicology and has more than 30 years experience dealing with complex regulatory issues related to product safety and risk assessment. He has in excess of 150 scientifi c publications in the fi elds of toxicology and risk assessment to his credit. Dr. Munro formerly held senior positions at Health Canada as Director of the Bureau of Chemical Safety and Director General of the Food Directorate, Health Protection Branch. While with the Health Protection Branch, Dr. Munro was responsible for research and standard setting activities of the Branch related to microbial and chemical hazards in food and the nutritional quality of the Canadian food supply. He contributed signifi cantly to the development of risk assessment procedures in the fi eld of public health, both nationally and internationally, through membership on various committees. A member of the Board of Directors of the Toxicology Forum, Dr. Munro also holds memberships in the Society of Toxicology and the American College of Toxicology. He has served on numerous national and international committees, including those of the World Health Organization, the International Agency for Research on Cancer, and the U.S. National Academy of Sciences. Dr. Munro is a graduate of McGill University in biochemistry and nutrition. He also holds a Ph.D. from Queen’s University in pharmacology and toxicology. Dr. Munro is a fellow of the Royal College of Pathologists, London. He was also Director of the Canadian Centre for Toxicology from 1983 to 1992 and is a professor in the Department of Nutritional Sciences Faculty of Medicine, University of Toronto.

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Nutritional Assessment of Foods Derived from GM CropsDr. B. Sivakumar, Director, National Institute of Nutrition, Hyderabad

Gene technology has been directed for production of economically more valuable products with nutritional quality than other conventional methods. Converting soybean to produce more essential amino acids and reducing the content of trypsin inhibitors, to transform sunfl ower or rapeseed to produce higher oleic acid or lauric acid, reducing the content of antinutritional factors in tomato and potato, and development of carotene-rich (golden rice) or carotene and iron-rich rice, are examples in value addition of foods through transgenic mechanisms.

For the biotechnologist and molecular biologist, the immediate concern at the time of development of technology is the success of the principle of value addition and not the extent of its likely benefi ts and the resultant health impacts on people. Th e next aspect for consideration is the safety of the food. Th erefore, concerns for wholesomeness of the food or nutritional and health evaluation is not generally built in as a part in the process of development of a GMO. However, at the end, all the eff ort to improve the nutritional quality and content may become futile and insignifi cant at the operational level, if the intended benefi ts for the consumer do not materialize. Th erefore, it is prudent to evaluate nutritional benefi ts along with, if not before, testing of safety aspects.

GM foods intended to improve nutritional qualtiy are currently undergoing trials. However, none of them have come to a stage that they are to be released for human consumption. While being strong in principle, the fruits of GM foods have to undergo testing for their safety and nutritional eff ectiveness. A case is made in the present review for treating the assessment of nutritional impact as an integral part of s̀afety evaluation’ to hasten the process. Th ough golden rice exhibited strong potential, nutritional evaluation exposed some limitations. At the earlier level of carotene enrichment achieved, golden rice falls too short in fi lling the gap of vitamin A intake in the benefi ciaries than GM oil, though in principle rice has more r̀each out’ than oil. In the background of the massive magnitude of the nutritional problems and constraints of time and resources operating, realistic dietary approaches should not be obscured by the promotion of only new technologies. In any case, the technology of GM foods is at the threshold of a new era, yet a long distance away from becoming a reality.

Dr. B. Sivakumar is currently holding the position of Director, National Institute of Nutrition (NIN), Indian Council of Medical Research (ICMR) Hyderabad, India and Head of the Biophysics Division at NIN. After completing his doctoral work at the Department of Biochemistry, Nagpur University, Nagpur (India) on “Role of reducing compounds in general metabolism” as a CSIR/JRF during 1966-69, he started his career at NIN in 1969 and his fi eld of specialization has been `Nutritional Biochemistry’.

Th e main area of interest has been vitamin A nutrition, covering aspects like methods of assessing vitamin A status, etiology of vitamin A defi ciency, carotenoid conversion and vitamin A absorption, turnover of vitamin A and its binding proteins and vitamin A requirements in pregnancy.

Other areas of his work include micronutrients and food fortifi cation.

He had visited London School of Hygiene & Tropical Medicine, UK (1990) and Children’s Nutrition Research Centre, Baylor College of Medicine, Houston, Texas, USA (1992 94) as Visiting Scientist.

He is recognized as a Ph.D. guide in Biochemistry by Osmania University, Mysore University, Bombay University and Nagpur University and guided 9 postgraduate students so far to their Ph.D. in Biochemistry. Member of

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the Board of Studies in Nutrition, Osmania University, Hyderabad. He has more than 100 research publica-tions to his credit. He is a Fellow of the Andhra Pradesh Academy of Sciences.

Important Contributions

Dr. Sivakumar’s Lab had used a nice blend of clinical and experimental fi ndings to provide strong functional and mechanistic insights into nutritional problems like vitamin A defi ciency and certain bone diseases, for developing appropriate interventions. Apart from showing recurring infections as major etiological factors of vitamin A defi ciency, interactions between vitamin A and protein metabolism were investigated. Using func-tional assessment, vitamin A requirements were worked out to be 750RE during pregnancy. New methodologies were developed for measuring intestinal conversion of dietary carotenoids to vitamin A and the signifi cance of horticultural development as a strategy to improve vitamin A defi ciency and anaemia in the community has been demonstrated.

Dr. Sivakumar has been awarded with Vepachedu Gopalakrishna Rao Endowment Award for the year 2005 by the Dept. of Biochemistry, Osmania University, Hyderabad. He is nominated for Shri Ramendra Sundar Sinha Memorial Oration, 2005 by the Physiological Society of India to be delivered during the 93rd Indian Science Congress in January 2006 at ANGRAU, Hyderabad.

31

GM Foods and Consumer Acceptance in AsiaMr. K.Keh Kok Leong, Asian Food Information Centre, Singapore

Background

Th e Asian Food Information Centre conducted quantitative survey in 2002 and qualitative focus group survey work in 2003 on consumer perceptions relating to food biotechnology.

Th ese surveys used relatively small sample sizes. However, it is noteworthy, that results from other surveys (conducted for BIOTEC, Th ailand 2004, ISAAA 2003) in the region have found remarkably similar results, and therefore AFIC recommends that the fi ndings and conclusions provide useful insight into the mindset knowledge base, and information needs of consumers in Asia.

Results of Consumer Perception Surveys

Th e 2002 survey conducted in China, Indonesia and Philippines, found knowledge levels about genetics and the general issue of biotechnology low. Increasing knowledge levels were associated with more posi-tive attitudes, but few of those interviewed had strong opinions either way. Indeed, the majority of those interviewed were found to have a very open-minded attitude to biotechnology with signifi cant interest in the opportunities and benefi ts the technology might off er: Over 80% of respondents indicated they would be willing to buy GM foods with improved nutrition, taste, freshness qualities, or to protect the environ-ment, and 88% responded that they would probably or defi nitely be willing to try a biotechnology-derived snack food at the time of interview.

In 2003, AFIC commissioned research using focus group discussions methods in the Philippines, China and India to gain greater understanding of consumer perceptions of biotechnology-derived foods, and identify appropriate language and communication channels for the issue.

Th e application of biotechnology to potentially produce foods with enhanced nutritional value or requiring less pesticide for cultivation, elicited very positive responses. Consumers found this information highly credible, and expressed desire for further information on such potential benefi ts.

Conversely, consumers were very unaware of prevailing concerns being debated within the inner circle of stakeholders, such as horizontal gene transfer, and were therefore not seeking information on safety and risk assessment. AFIC tested multiple risk messages, but found that unsolicited provision of information on safety assessment standards, rationale and process did not appear to improve knowledge levels or stimulate interest, but instead raised anxiety no matter how the information was presented.

Consumers identifi ed the mass media e.g. television, radio, newspapers, magazines and advertisements, etc, as preferred communication channel.

Scientists and academics, as well as inter-governmental organisations such as FAO and WHO were perceived to be the most neutral and credible parties to disseminate information on food biotechnology through these channels. Government information providers were also regarded positively, although less than academic institutions or the UN agencies.

Recommendations for Action

Based on AFIC’s own surveys and also those of other organisations based in the region, AFIC off ers the following recommendations:

Potential consumer benefi ts of biotechnology foods are used as the cornerstone message or as the introduction to the topic.

•

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Information should be presented in context and balanced, providing very basic information about the technology, agriculture, plant breeding and genetics, and avoiding extreme, or value-based statements and commentary.

Information about risk assessment must be available but best presented/positioned as background information for those who wish to extend knowledge and understanding.

A broad collection of stakeholders have a role to play: including mass media, intergovernmental or-ganisations, academia, governments departments, and communication specialists. More systematic co-operation and collaboration could provide synergy and progress the considerable and to date largely unfulfi lled challenge of improving public understanding.

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•

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35

Public Perception of GM Foods in IndiaDr. Suman Sahai, Gene Campaign

Suman Sahai, who has had a distinguished scientifi c career in the fi eld of genetics, was honored with the 2004 Borlaug Award for her outstanding contribution to agriculture and the environment. Dr. Sahai received her Ph.D. degree in genetics from the Indian Agricultural Research Institute in New Delhi. From 1981 to 1989, she served as a faculty member at the University of Alberta in Canada, University of Chicago in the U.S., and the University of Heidelberg in Germany. Dr. Sahai returned to India in 1989 and organized Gene Campaign, a non-governmental organization dedicated to protecting farmers’ rights and food and livelihood security. Gene Campaign which has played a key role in formulating Farmers’ Rights and fostering genetic and trade literacy among farmers and the general public, has been at the forefront of generating awareness on issues relating to trade, intellectual property rights, and genetic resources conservation and sustainable use.

Dr. Sahai, who has published extensively in science and policy issues related to food security, has been working both at the grassroots and policy levels, with great dedication and considerable impact. She is a member of sev-eral national policy forums on international trade, biodiversity and environment, biotechnology and bioethics, intellectual property rights and research and education. She is a member of the National Biodiversity Board and serves on the Research Advisory Committees of national scientifi c institutions, the high-powered National Commission on International Trade and the Ethics Committee of the Indian Council of Medical Research.

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Public Perception of GM Foods in IndiaDr. Sri Ram Khanna, Consumer Voice

Biotechnology undoubtedly has a big potential to bring about immense benefi ts in the near future. Yet, there are concerns about certain aspects of biotechnology and one such aspect is genetic modifi cation (GM). Consumers have a considerable amount of suspicion and confusion regarding GM foods especially in the absence of GM labelling. To make matters worse, even scientists are skeptical about GM foods. Th e case for biotechnology states that it off ers an advantage in developing countries because it can increase agricultural production and help meet the global food demand; it can improve the environment and reduce the use of chemicals and pesticides and perhaps use less water, making agriculture less input intensive. Appropriate farm technologies may increase farm incomes as well as employment opportunities for landless rural households and they have the potential to help resolve the problem of health and undernourishment. So, biotechnology can be an engine for future growth.

Although much concern is being expressed about biotechnology, part of the fear is adverse health impacts particularly over long-term; potentially adverse environmental impacts especially in the biodiversity-rich tropics; and other socio-economic impacts.

Adding to the confusion, there is a strong need to develop a National Biosafety Framework which is a combination of legal, administrative and technical instruments which will be eff ective to address issues of safety for the environment and human health. To safeguard consumers’ rights and interests, labelling of GMOs and GM foods should be mandatory.

If the future of biotechnology is to be really relevant to Indian conditions, there is a need to develop networking and collaborated work in public sector labs and concerned institutions to get outcomes that favour development in developing countries.

Prof. Khanna has been a part of consumer movement since 1983, when VOICE was set up. He is a member of the National Codex Committee, Central Consumer Protection Council, Government of India and a Council Member of consumers International (CI), UK. He served as the Vice Chairman of Consumer Coordination Council, a national level apex body of 55 leading consumer organizations in the country, for more than three years. He has represented the consumer viewpoint in several bodies over the past decade. In recent past he had been an active member of LIC, Consumer Policy Committee (COPOLCO), BIS.

He participated in various Codex Committee meetings to represent India and Asia’s views. Participated and chaired several workshops relating to Consumer Interest, Food Safety and Environment.

Presently he is actively engaged in issues like Food Safety and Standards Bill and GM Foods to safeguard con-sumer interest.

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Consumer Labelling and Traceability RegimesDr. S.R. Rao, OSD to Minister of Science and Technology, Government of India

Th e subject of GM food is continuously debated in terms of technology inherent and technology tran-scending issues of biosafety, commercialization and public acceptance. Besides the Cartagena Protocol on Biosafety and FAO-WHO Codex discussions on labelling, the concepts of co-existence, identity preserva-tion and traceability are emerging as international policies. Th e international trade rules set by the WTO, particularly the agreements on Technical Barrier to Trade (TBT), Sanitary and Phytosanitary Measures (SPS), and Pre-shipment Inspection (PSI) have further complicated the food trade. In view of the above developments, an attempt is made to appraise the current experiences on labelling and traceability issues in India and abroad. Relevant policy issues, institutional framework, trade economics, research needs, requirement of infrastructure and technical expertise and public perception are discussed, keeping in view developing economies.

Dr. S.R. Rao, Director, Department of Biotechnology is currently an Offi cer on Special Duty to the Minister of Science & Technology and Ocean Development, Government of India. He is a graduate in Agriculture with a Ph.D. in Mycology and Plant Pathology from Indian Agricultural Research Institute, New Delhi. He was a post Doctoral Fellow at Tottori University, Japan and visiting Scientist at Waite Agricultural Experimental Station, Adelaide, Australia and specializes in molecular pathology. He has served in various positions in the Department of Biotechnology, Government of India since 1989 and was actively involved in establishment of oil palm cultivation in India, several sophisticated biotech infrastructure facilities, forging bilateral collabora-tion with Asian and European countries, the introduction of Golden rice for research in India and biotech policy, planning and budgetary matters. He is a member of several technical committees, academic councils of universities, Asia in UNEP-GEF Steering Advisory Committee on Capacity Building of Cartagena Protocol Secretariat, Montreal; Liaison Group on Capacity Building of Protocol. He specializes in core and cross-sectoral policy issues of biotechnology and has published 25 research papers in national/international journals and has made 50 presentations at various national and international conferences.

41

Consumer Labelling and Traceability RegimesDr. C. Kameswara Rao, Executive Secretary, Foundation for Biotechnology Awareness and Education

Labelling commercialized products dates back to the times of the Roman Empire. Over the centuries the product label has become a means of product identifi cation, establishing Intellectual Property Rights and market position, by the manufacturer. For the authorities labelling is a tool of protecting consumer interests and of tracing the antecedents of the product, to check any regulatory violations by the manufacturer and the marketing outlets. Over the years, labelling, a simple means of providing information to the consumer to make educated choices, became a very complex and contentious issue, in almost every sphere.

Plants and animals that are source of food and feed, are genetically engineered (GE) to enhance fl avour, quality and yield, to increase nutrients, and to improve resistance to pests and diseases. GE plants and animals have turned out to be one of the most controversial issues today, as the opponents of technology have raised questions of safety and the ethics behind such technology.

Labelling and traceability regulations for non-GE food products have existed for decades in almost every country. All countries that are involved in the development, cultivation and marketing of GE crops, have now a regulatory frame work for consumer safety of food derived from GE plants and animals. A uniform international policy is essential to smooth international trade in such products. Procedures and regulations of testing GE foods for diff erent safety parameters and mandatory labelling practices, to facilitate traceability of a food product to its genetic and production source, have unfortunately become international controversies.

Th e Food and Drug Administration of the United States is satisfi ed with the establishment of substantial equivalence between a GE product and its isogenic line, and does not have mandatory labelling regulations. However, labels and symbols for GE foods, are used voluntarily in the US, to indicate if a product is ‘GM free’. Th e tag ‘Identity Preserved’ is used to refer to the record of a product’s specifi c traits through the entire process from the crop to the product.

Th e European Union has detailed regulatory procedures, to ensure the safety of GE food products to the consumers and labelling to provide product information to both the user and the authorities. Th e EU’s regulations are so stringent that they sparked protests from the product developers and raised doubts whether any GE product will at all qualify to be considered safe under these regulations.

Codex Alimentarius Commission (CAC) is the international organization established in 1963, jointly by the FAO and WHO, under the Food Standards Programme. CAC is an inter-governmental body whose membership is open to all Member Nations and Associate Members of FAO/WHO, and currently com-prises of over 165 countries. International non-governmental organisations, such as consumer, academic or industry bodies, may attend Codex meetings as observers.

Th e objectives of CAC are, protecting health of the consumers, ensuring fair trade practices in the food trade, and promoting co-ordination of all food standards work undertaken by international governmen-tal and non-governmental organizations. Th e Codex has framed detailed policy guidelines to establish safety of products of modern biotechnology and foods derived through GE plants and micro-organisms. However, a number of gray and confl icting areas dog consensus.

Th e Cartagena Protocol is not relevant to food safety and labelling issues as it is primarily concerned with international trans-boundary movement of GE plants and animals and neither with foods nor their label-ling.

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Some of the much debated questions are:

what kind of label would serve the objective of consumer and regulatory needs?

should it be linguistic or symbolic or a combination of the two?

what a label should include?

should it be mandatory or voluntary?

what is the threshold of GE content in a food product?

should refi ned products derived from GE plants and animals, but do not contain any GE component be regulated?

what kind of scientifi c procedures should be adopted in the qualitative and quantitative analysis of GE component in foods?

In multilingual countries, the choice of languages in providing label information is also a serious emotionally charged question. At the end of all this time consuming and expensive exercise, the question that remains is, ‘how many consumers actually read the label information and are guided by it in their choice?’.

Many countries that introduced labelling have already been threatened under WTO trade agreements, for example, the EU by the US.

In India, the ‘Prevention of Food and Adulteration Act’ of 1954 was aimed to prevent the adulteration and misbranding of food. Th e label was required to indicate the name or description of the food, the name and business address of the manufacturer or importer, the net weight of the food, ingredients, batch/code number in Hindi or English (or regional languages), the month and year of manufacture, packing and expiry and if preservatives, coloring agents, antioxidants, or vitamins have been added to the food.

India should now consider framing internationally compatible regulations on labelling and traceability of GE food products. Th e issues have to be addressed case-by-case basis.

Th e only GE crop now grown in India is Bt cotton and it has no serious implications for use as food. Th ough there are several GE crops in development, no GE food product is likely to emerge in India in this decade. Framing rules for labelling and traceability of GE foods at this point of time would be without a focus. However, it would immensely benefi t, if a working group reviews the provisions of international instruments and the regulations adopted in diff erent countries and draft a basic policy, with a provision to suitably modify as and when a GE product would reach the market. Th is process will be a little easier if the working group has authentic information on the probable datelines of release of diff erent GE products, both in the public and private sectors. Th e product developers and stakeholders should be involved in the process in order to arrive at consensus.

Prof. Chavali Kameswara Rao is the Executive Secretary, Foundation for Biotechnology Awareness and Education (FBAE), Bangalore. Prof. Rao has a Ph.D. in Botany from the Andhra University. He started his career in teaching as a Lecturer in Botany (1965) at Andhra University; and served the Bangalore University from June 1967 to April 1998. He was awarded an honorary D.Sc. by the Open International University for Alternative Medicine, Colombo and a Certifi cate of Merit from the Lama Gangchen World Peace Foundation, Beijing. Prof. Rao was Commonwealth Academic Staff Fellow (1980-81), Royal Society and Nuffi eld Foundation Bursar (1983-84). He also worked at the Natural History Museum, London, Royal Botanic Gardens, Kew, and Royal Botanic Gardens, Edinburgh, UK, and National Museum of Natural History, Paris (France), on computer ap-

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plications in Plant Systematics, and produced online packages for the identifi cation of South Indian Dicot Families and the World Monocot Families. Over 17 years Prof. Rao studied lectins and saponins in medicinal plants and compiled a database of medicinal plants. Prof. Rao is member in various important committees including the committee on ‘Advances in Technology and the Prevention of their Application to Next Generation Biowarfare’, US National Academies, Washington, D.C. He is also member, Working Group on Public Understanding and Trust, Task Force for National Policy on Biotechnology, Department of Biotechnology, Government of India.

45

Assessing the Safety of Nutritionally Enhanced GM FoodsDr. Vandana Shiva, Navdanya

Dr. Vandana Shiva, is Director, Research Foundation for Science, Technology and Ecology, and Vice-President, Th ird World Network. She received her Ph.D. degree from University of Western Ontario in Physics. Dr. Shiva has been a visiting professor and lectured at several Universities, Organizations and Institutions worldwide on ecology, feminism and globalization. Dr. Shiva has received many awards for her contributions to deepening the ecological paradigm and for linking research to action. She is chair of the International Commission on the Future of Food. She is on the Advisory Board of Green Institute, Washington D.C. USA and the Center for Food Safety, Washington DC. In 1991, she founded Navdanya, a national movement to protect the diversity and integrity of living resources, especially native seeds, the promotion of organic farming and fair trade.

47

Assessing the Safety of Nutritionally Enhanced GM FoodsDr. Ian Munro, CANTOX Health Sciences International, Canada

Th ere is increasing interest in enhancing the nutritional quality of foods. New nutritionally enhanced foods derived through modern biotechnology have the potential to alleviate nutritional defi ciencies, improve the overall nutritional quality of the diet and provide a reliable source of nutrients for addition to traditional foods. Th e safety standard applied to these nutritionally improved varieties is similar to that applied to fi rst generation GM crops with enhanced agronomic traits. Th e key focus of the safety evaluation is comparative compositional analyses, which is intended to ensure the new variety is as safe as its traditional counterpart. Since new nutritional improved varieties are intended to replace existing varieties it is important that the intended use of the new variety in the food supply be known and evaluated. To accomplish this an intake analysis is required to determine how much of the new variety would be consumed by various segments of the population. Th is is to ensure that the nutritionally enhanced variety is reaching the intended popula-tion and providing the additional source of nutrients.

Dr. Munro is an internationally recognized authority on toxicology and has more than 30 years experience dealing with complex regulatory issues related to product safety and risk assessment. He has in excess of 150 scientifi c publications in the fi elds of toxicology and risk assessment to his credit. Dr. Munro formerly held senior positions at Health Canada as Director of the Bureau of Chemical Safety and Director General of the Food Directorate, Health Protection Branch. While with the Health Protection Branch, Dr. Munro was responsible for research and standard setting activities of the Branch related to microbial and chemical hazards in food and the nutritional quality of the Canadian food supply. He contributed signifi cantly to the development of risk assessment procedures in the fi eld of public health, both nationally and internationally, through membership on various committees. A member of the Board of Directors of the Toxicology Forum, Dr. Munro also holds memberships in the Society of Toxicology and the American College of Toxicology. He has served on numerous national and international committees, including those of the World Health Organization, the International Agency for Research on Cancer, and the U.S. National Academy of Sciences. Dr. Munro is a graduate of McGill University in biochemistry and nutrition. He also holds a Ph.D. from Queen’s University in pharmacology and toxicology. Dr. Munro is a fellow of the Royal College of Pathologists, London. He was also Director of the Canadian Centre for Toxicology from 1983 to 1992 and is a professor in the Department of Nutritional Sciences Faculty of Medicine, University of Toronto.

49

Postharvest Monitoring of Foods Modifi ed by New Genetic Modifi cation TechniquesDr. Christine M. Bruhn, University of California-Davis, USA

Enhanced public health and welfare should be the guiding principles for production and sale of any food, whether modifi ed by genetic rngineering or conventional processes. Genetically modifi ed (GM) food in-troduced in to the marketplace should undergo a thorough safety assessment so the likelihood of ill eff ect upon introduction is very small.

Th e fi rst step in safety monitoring should be appropriate risk assessment. “Substantial Equivalence” an important element in GM food safety assessment, compares a genetically modifi ed product with one having an acceptable standard of safety. Th is principle states that GM foods can be considered as safe as conventional foods when key toxicological and nutritional components of the GM food are comparable to the conventional food. Th is principle recognizes that conventional foods may have low levels of natural toxins and accepts the GM food as comparably safe if the natural toxins do not exceed that level found in commercial products.

Codex Alimentarious Commission July 2003, Principles for the risk analysis of foods derived from modern biotechnology outlines basic principles of pre-market assessment. Th e Codex safety assessment requires evaluation of direct health eff ects, tendency to provoke allergic reaction, level of specifi c components with nutritional or toxic properties, stability of the inserted gene, nutritional eff ects associated with the specifi c genetic modifi cation, and any unintended eff ects which could result from gene insertion. Pre-market studies may include in vitro and in vivo evaluations of toxicological eff ects, potential allergenicity and nutrition following recommended standard methods. Testing includes establishing natural baselines variations and the eff ect of growing conditions and environmental infl uences. Signifi cant evidence on the potential toxicity of chemical components is in the literature based on animal experiments.

Public information is critical for introduction and monitoring of GM foods. Food has important societal and cultural roles. Appropriate channels should be used to involve the public early in identifying problems that newer techniques of GM can remedy, and establishing a framework that addresses the safety and appropriateness of any modifi cation. Th erefore, clear communication of the benefi t provided by the new product placed in the appropriate cultural or historic perspective is critical to market acceptance.

Since reasonable assurance of safety is established in pre-market review, post-market monitoring may be used to correlate dietary intake of nutritionally improved food with expected health benefi ts. Accurate food consumption data and health assessment are necessary to document dietary benefi ts. Identifying positive or negative eff ects on health must be based on hypotheses with identifi ed biomarkers for measure-ment. Current exposure assessment principles can be used in post-market monitoring of GM foods to obtain consumption estimates and confi rm any pre-market predictions. Th is information may require traceability from fi eld to consumer. Post-market monitoring may also confi rm pre-market consumption projection and refi ne data on consumption by specifi c population groups. Labelling of GM crops may assist in traceability, however mandatory labels, unless carefully tested to address potential misconceptions, could lead to product avoidance.

Potential benefi ts of genetic modifi cation are extensive. Guidelines to assess and insure safety and to monitor dietary impact should not be so onerous that the benefi ts are never realized.

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Dr. Bruhn has expertise in consumer behavior, food science, and consumer economics. She taught food science and consumer courses at the University of California and California State University before joining Cooperative Extension in 1986. As a Consumer Food Marketing Specialist, Dr. Bruhn studies consumer attitudes toward food safety and quality and conducts educational programs that inform consumers about new products and new technologies. She is past chair of the Food Science Communicators and the Nutrition Division of the Institute of Food Technologists, and served as a Scientifi c Lecturer for the Institute, from 1992-97 and 2002-2003. Research conducted by the Center for Consumer Research generates knowledge that lays the basis for eff ective decision making by consumers at a personal level and for eff ective policy and actions by public and private organizations. Dr. Bruhn has authored over one hundred professional papers on consumer attitudes toward food. She receives numerous national and international requests to address consumer issues.

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Public Consultation in Decision Making in Australia and New Zealand.Mrs. Lydia Buchtmann, Food Standards Australia New Zealand, Australia

Food regulation cannot take place eff ectively in isolation without public consultation. Consumers, especially in western societies, are becoming more and more focussed on health issues and the food they eat. Food Standards Australia New Zealand (FSANZ)has an open process for setting food standards, including rounds of public comment. Th e standard for carrying out pre-market safety assessments of genetically modifi ed food came into force in Australia and New Zealand in 1998. However, Australian and New Zealand consumers wanted more than just the reassurance that a safety assessment had been carried out. Th ey wanted the control to make informed choices about whether they consume GM food or not. In 2000, labelling requirements were adopted for GM food requiring food to be labelled as being genetically modifi ed if it has altered DNA or protein in the fi nal product or altered characteristics diff erent to the conventional food.

Th e challenge for FSANZ (and other food regulators) is to close the information gap between the perceived risk held by the public and the actual scientifi c risk. In some cases, such as GM food, the public’s perceived risk is far higher than scientifi c assessed risk, provided a safety assessment has been carried out. In other cases, such as food poisoning, the public’s perceived risk is much lower than the scientifi cally assessed risk. For example, even in a westernised country like Australia there is still a one in four chance of getting food poisoning each year. FSANZ has a standard development process that separates the scientifi c risk assessment from the risk management process and includes risk communication from the beginning of each project. Much of the role of the risk communicators at FSANZ is to assist risk managers to consult with the public and other stakeholders and to work on closing the gap between real and perceived risk.

Lydia Buchtmann is the Communication Manager for Food Standards Australia New Zealand, the food stand-ards setting agency for Australia and New Zealand. She has been in that role for 8 years and is responsible for driving risk communication within the organisation, with a particular interest in communicating to consumers the diff erence between perceived risk and the actual scientifi c risk. She has had more than 20 years experience as a professional communicator both as a journalist and in the public sector as Director of Public Aff airs for the Australian Taxation Offi ce and the Federal Attorney-General’s Department. She has a Masters in Communication by Research specialising in indigenous communication.

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Challenges in Decision Making: Th e Indian Context Dr. G.S. Toteja, Deputy Director General, Indian Council of Medical Research, New Delhi

Decision-making in the fi eld of genetically modifi ed Foods is a challenging task. It involves policy makers, administrators, legislators, judiciary, industry, farmers and media. Technology for producing genetically modifi ed foods for benefi ts of farmers and consumers is useful; however, safety of consumers is an important issue. Inadequate long-term safety data and uncertainties regarding possible impact of genetically modifi ed foods on the environment pose a real challenge to take policy decision. Th e formulation of guidelines for research in genetically modifi ed plants, their experimental fi eld trials, regulatory framework and stand-ards for risk assessment are in the process. Co-ordination among various agencies such as Department of Biotechnology, Ministry of Environment, Ministry of Health & Family Welfare, Ministry of Agriculture is a bottle neck.

Mechanism for feedback from farmers and consumers and periodical review needs to be developed to ease decision-making process.

Dr. G. S. Toteja has been working in Indian Council of Medical Research Headquarters, New Delhi, India for more than two decades. Currently, he is Deputy Director General and looking after research programmes related to Nutrition and Food Safety. He has been actively working in the fi eld of Micronutrients, Genetically Modifi ed Foods, and food Contaminants/Adulterants. He has also been making sincere eff orts to promote research in North-East Region of India and also facilitating health delivery by community participation among un-reached tribal populations. His interest has also been to work for slum dwellers and develop capacity of young scientists to carry research in the fi eld of Nutrition.

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Dr. Vibha Ahuja1 and Dr. Geeta Jotwani2

1 Deputy General Manager, Biotech Consortium India Limited, 5th Floor, Anuvrat Bhawan, 210, Deen Dayal Upadhyaya Marg, New Delhi-110 002, Email: [email protected]; [email protected] Senior Research Offi cer, Division of Basic Medical Sciences, Indian Council of Medical Research, Ansari Nagar, P.B.No. 4911, New Delhi-110 029, Email: [email protected]

INTRODUCTION

Th e global demand for food is increasing because of the growing world population and decreasing arable land. At the same time food and agricultural systems have to respond to several changes such as increasing international competition, globalization and rising consumer demands for improved food quality, safety, health enhancement and convenience. Modern biotechnology involving the use of rDNA technology/genetic engineering has emerged as a powerful tool with many potential application for improving the quantity and quality of food supply. Foods derived from genetically modifi ed crops, commonly referred to as geneti-cally modifi ed food and food ingredients have already become available worldwide with aim of enhancing productivity, decreasing the use of certain agricultural chemicals, modifying the inherent properties of crops, improving the nutritional value or even increasing shelf life.

As more and more GM crops are being developed and released for fi eld-testing and commercialization, concerns have been expressed about the potential risks associated with their impact to human health, environment and biological diversity. Th ese apprehensions arise because genetic engineering crosses the species barrier as compared to classical selection techniques, thereby permitting the gene transfer among microorganisms, plants and animals, although there is no evidence that any unique hazards exist in the development of GM, because of novel combinations of genes.

Further the concerns in agriculture do not necessarily lie with the characteristics of the products but rather with the way it is produced particularly in case of food crops. Any innovation in the process of production of crops particularly the food crops, raises suspicion particularly with consumers and food experts.

Th erefore biosafety legislation and regulatory institutions to implement them have been put in place by many countries including India, both for research and trade of GM crops and food and food ingredients derived from them. Th ere are elaborate steps to manage these risks and it is the responsibility of the scientists, industry, and the government to assure the public of the safety of the novel food products com-mercialized.

A brief overview of rules and regulations in India relevant for foods derived for GM crops (GM foods) is presented here:

Background Note: The Regulation of Genetically Modifi ed Organisms

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GOVERNMENT RULES FOR GMOs

Th e regulatory framework for transgenic crops in India consists of the following rules and guidelines.

Rules and policies Rules 1989 under Environment Protection Act (1986)Seed Policy 2002

Guidelines Recombinant DNA guidelines, 1990Guidelines for research in transgenic crops, 1998

Rules, 1989

Th e Ministry of Environment & Forests, Government of India notifi ed the rules and procedures for the manufacture, import, use, research and release of genetically modifi ed organisms (GMOs) as well as prod-ucts made by the use of such organisms on December 5, 1989 under the Environmental Protection Act 1986 (EPA). Th ese rules and regulations, commonly referred as Rules 1989 cover the areas of research as well as large scale applications of GMOs and products made therefrom throughout India. A copy of the rules can be accessed at http://envfor.nic.in.

Th e Rules, 1989 order compliance of the safeguards through regulatory approach and any violation and non-compliance including non-reporting of the activity in this area attracts punitive action provided under the EPA.

Th e two main agencies responsible for implementation of the rules are the Ministry of Environment and Forests (MoEF) and the Department of Biotechnology (DBT), Government of India. Th e rules have also defi ned competent authorities and the composition of such authorities for handling of various aspects of the rules. Th ere are six competent authorities as per the rules:

Recombinant DNA Advisory Committee (RDAC)

Review Committee on Genetic Manipulation (RCGM)

Genetic Engineering Approval Committee (GEAC)

Institutional Biosafety Committees (IBSC)

State Biosafety Coordination Committees (SBCC)

District Level Committees (DLC).

Out of these, the three agencies that are involved in approval of new transgenic crops are:

IBSC set-up at each institution for monitoring institute level research in genetically modifi ed organ-isms.

RCGM functioning in the DBT to monitor ongoing research activities in GMOs and small scale fi eld trials.

GEAC functioning in the MoEF to authorize large-scale trials and environmental release of GMOs.

Th e Recombinant DNA Advisory Committee (RDAC) constituted by DBT takes note of developments in biotechnology at national and international level and prepares suitable recommendations. Th e State Biotechnology Coordination Committees (SBCCs) set up in each state where research and application of

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GMOs are contemplated, coordinate the activities related to GMOs in the state with the central ministry. SBCCs have monitoring functions and therefore have got powers to inspect, investigate and to take punitive action in case of violations. Similarly, District Level Committees (DLCs) are constituted at district level to monitor the safety regulations in installations engaged in the use of GMOs in research and application.

Th e approvals and prohibitions under Rules 1989 are summarized below:

No person shall import, export, transport, manufacture, process, use or sell any GMOs, substances or cells except with the approval of the GEAC.

Use of pathogenic organisms or GMOs or cells for research purpose shall be allowed under the Notifi cation, 1989 of the EPA, 1986.

Any person operating or using GMOs for scale up or pilot operations shall have to obtain permis-sion from GEAC.

For purpose of education, experiments on GMOs IBSC can look after, as per the guidelines of the Government of India.

Deliberate or unintentional release of GMOs not allowed.

Production in which GMOs are generated or used shall not be commenced except with the approval of GEAC

GEAC supervises the implementation of rules and guidelines.

GEAC carries out supervision through SBCC, DLC or any authorized person.

If orders are not complied, SBCC/DLC may take suitable measures at the expenses of the person who is responsible.

In case of immediate interventions to prevent any damage, SBCC and DLC can take suitable measures and the expenses incurred will be recovered from the person responsible.

All approvals shall be for a period of 4 years at fi rst instance renewable for 2 years at a time.

GEAC shall have powers to revoke approvals in case of:

Any new information on harmful eff ects of GMOs.GMOs cause such damage to the environment as could not be envisaged when approval was given.Non-compliance of any conditions stipulated by GEAC.

Recombinant DNA Guidelines, 1990

With the advancement of research in biotechnology initiated by various Indian institutions and industry, Department of Biotechnology had formulated Recombinant DNA Guidelines in 1990. Th ese guidelines were further revised in 1994 to cover R&D activities on GMOs, transgenic crops, large-scale production and deliberate release of GMOs, plants, animals and products into the environment, shipment and im-portation of GMOs for laboratory research.

For research, the guidelines have been classifi ed into three categories, based on the level of the associated risk and requirement for the approval of competent authority:

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Category I activities include those experiments involving self cloning using strains and also inter-spe-cies cloning belonging to organism in the same exchanger group which are exempt for the purpose of intimation and approval of competent authority.

Category II activities which require prior intimation of competent authority and include experiments falling under containment levels II, III and IV (details of each containment level provided separately in the guidelines).

Category III activities that require review and approval of competent authority before commencement include experiments involving toxin gene cloning, cloning of genes for vaccine production, and other experiments as mentioned in the guidelines.

Th e levels of risk and classifi cation of the organisms within these categories have been defi ned in these guidelines. Appropriate practices, equipment and facilities necessary for safeguards in handling organisms, plants and animals in various risk groups have been recommended. Th e guidelines employ the concept of physical and biological containment and the principle of good laboratory practices.

For containment facilities and biosafety practices, recommendations in the WHO laboratory safety manual on genetic engineering techniques involving microorganisms of diff erent risk groups have been incorporated therein.

Th e guidelines categorize experiments beyond 20 liters capacity for research and industrial purposes as large-scale. In case of cultivation of plants, this limit is 20 acres area. Th e guidelines give principles of oc-cupational safety and hygiene for large-scale practice and containment. Safety criteria have also been defi ned in the guidelines. Physical containment conditions that should be ensured for large-scale experiments and production have been specifi ed in the guidelines.

For release to the environment the guidelines specify appropriate containment facilities depending on the type of organisms handled and potential risks involved. Th e guidelines require the interested party to evaluate rDNA modifi ed organism for potential risk prior to application in agriculture and environment like properties of the organism, possible interaction with other disease causing agents and the infected wild plant species. An independent review of potential risks should be conducted on a case-to-case basis. A copy of the guidelines can be accessed at http://www.dbtindia.nic.in.

Guidelines for Research in Transgenic Plants, 1998

In 1998, DBT brought out separate guidelines for carrying out research in transgenic plants called the Revised Guidelines for Research in Transgenic Plants. Th ese also include the guidelines for toxicity and allergenicity of transgenic seeds, plants and plant parts.

Th ese guidelines cover areas of recombinant DNA research on plants including the development of transgenic plants and their growth in soil for molecular and fi eld evaluation. Th e guidelines also deal with import and shipment of genetically modifi ed plants of research purposes.

Genetic engineering experiments on plants have been grouped under three categories.

Category I includes routine cloning of defi ned genes, defi ned non-coding stretches of DNA and open reading frames in defi ned genes in E. coli or other bacterial/fungal hosts which are generally considered as safe to human, animals and plants.

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Category II experiments include experiments carried out in lab and green house/net house using defi ned DNA fragments non-pathogenic to human and animals for genetic transformation of plants, both model species and crop species.

Category III includes experiments having high risk where the escape of transgenic traits into the open environment could cause signifi cant alterations in the biosphere, the ecosystem, plants and animals by dispersing new genetic traits the eff ects of which cannot be judged precisely. Th is also includes experiments having risks mentioned above conducted in green houses and open fi eld conditions.

To monitor the impact of transgenic plants on the environment over a period of time, a special Monitoring and Evaluation Committee (MEC) has been set up by the RCGM. Th e committee undertakes fi eld visits at the experimental sites and suggests remedial measures to adjust the trial design, if required, based on the on-the-spot situation. Th is committee also collects and reviews information on the comparative agro-nomic advantages of the transgenic plants and advises the RCGM on the risks and benefi ts from the use of transgenic plants under evaluation.

Th e guidelines include complete design of a contained green house suitable for conducting research with transgenic plants. Besides, it provides the basis for generating food safety information on transgenic plants and plant parts.

A copy of the guidelines can be accessed at http://www.dbtindia.nic.in.

Seed Policy, 2002

Th e Seed Policy 2002 issued by Ministry of Agriculture, Government of India contains a separate section (No. 6) on transgenic plant varieties. It has been stated that all genetically engineered crops/varieties will be tested for environment and biosafety before their commercial release as per the regulations on guidelines of the EPA, 1986. Seeds of transgenic plant varieties for research purposes will be imported only through the National Bureau of Plant Genetic Resources (NBPGR) as per the EPA, 1986. Transgenic crops/varieties will be tested to determine their agronomic value for at least two seasons under the All India Coordinated Project Trials of ICAR, in coordination with the tests for environment and bio-safety clearance as per the EPA before any variety is commercially released in the market. After the transgenic plant variety is com-mercially released, its seed will be registered and marketed in the country as per the provisions of the Seeds Act. After commercial release of a transgenic plant variety, its performance in the fi eld, will be monitored for at least 3 to 5 years by the Ministry of Agriculture and State Departments of Agriculture.

It has also been mentioned that transgenic varieties can be protected under the PVP legislation in the same manner as non-transgenic varieties after their release for commercial cultivation. A copy of seed policy can be accessed at http://agricoop.nic.in/seedpolicy.htm.

Th e procedures involved in the approval of GM crops in India are summarized in the following fl ow chart:

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Source: Dr. T.V. Ramanaiah, Director, Department of Biotechnology

FOOD CONTROL SYSTEM

As the Government has the prime responsibility for the establishment and operation of national food safety programs and quality control systems that must ensure safe and wholesome food to meet the nu-tritional needs of consumers and do not endanger the consumer’s health through chemical, biological or other contaminants, it has set up a ‘food control system’ that includes the national, state and municipal organizations involved in either the regulation, inspection or analysis of food and agricultural products, together with their supporting legislation and rules and compliance activities.

Prevention of Food Adulteration Act

In India, the Ministry of Health and Family Welfare (MOH&FW) in the Central Government is the nodal Ministry for ensuring the quality and safety of food marketed in the country. A comprehensive legislation called the Prevention of Food Adulteration Act (PFA Act) has been enacted in 1954, which came into eff ect from June 1, 1955, with the objective of assuring the quality and safety of food as well as to encourage fair trade practices.

Th e Act has been amended a number of times to make the provisions more practical and consumer-oriented. Th is Act is the basic statute intended to protect the consumer from the supply of adulterated food and it specifi es food safety and quality standards for consumer protection. Th e defi nition of ‘adulteration’ includes the addition of cheaper or inferior substances to deceive the consumer and the presence of contaminants, which may make the food, unfi t for human consumption. Th e objective of this legislation is, therefore, not only to ensure pure and wholesome food to the consumers, but also to prevent fraud or deception. It lays down that no person shall manufacture, sale, store, or distribute adulterated or misbranded food products not conforming to the standards laid down in the rules. Th e provisions apply to imported food as well as to food produced in India.

Applicant

RCGM

IBSC

MEC

GEAC ICAR

Seeds Act/Rules

RCGM functionsTo note, approve, recommend generation of appropriate biosafety & agronomic data

GEAC functions:To approve for large scale use,

open release in to environment

To inform decision to Ministry of Agriculture & to inform applicants to follow the

relevant Acts and Rules

IBSC functionsTo note, approve, recommend &

to seek approval of RCGM

MEC functionsVisit trial sites, analyze data, inspect facilities,

recommend safe and agronomically viable transgenics to RCGM/GEAC

ICAR TrialsTo generate complete agronomic data

and to recommend for commercial release of GM crops

Release for commercial agriculture

63

Th e overall infrastructure includes the local food inspectors, the public analysts, both at the municipal and state levels, their laboratory facilities, the four central food laboratories designated under the PFA Act and the central PFA Division in the MOH&FW in New Delhi. Th e central PFA Division is also designated as the National Codex Contact Point for India.

Source: A contemporary approach to food quality and safety standards; Ministry of Health and Family Welfare available at http://www.codexindia.nic.in

Th e responsibilities of the PFA cell in food control system are as follows:

Enhance the availability of safe and wholesome food.

Consumer protection from deception, fraud and food-borne diseases.

Risk analysis, risk management and risk communication.

Ensure safety of genetically modifi ed food.

Enhance the involvement of NGOs and Home Science Institutes.

Educational authorities to ensure better consumer protection.

Promote a voluntary management system, the Code of Ethics, through principles of GMPs and the HACCP.

Regarding laboratory facilities under the PFA Act, there are approximately 80 food laboratories in the country undertaking the analysis of samples of food articles under the provisions of the PFA Act, out of which 13 are managed by local bodies (municipalities). Th ese are known as Public Analyst Laboratories. In addition, there are four Central Food Laboratories notifi ed under the PFA Act to carry out an analysis of appeal samples whenever the report of the public analyst is challenged in the court of law. Th ese are situated in Kolkata, Ghaziabad, Mysore and Pune. Th ese laboratories analyze the bulk of the samples under the PFA Act.

1.

2.

3.

4.

5.

6.

7.

FFooood d Safety and y and Qualiuality y Control Ool Organizganizatiotion

Ministry of Health and Family Welfare

Director General of Health Services

PFA Cell

State/Governments/UTs

CentralCommitteefor FoodStandards andits Sub-Committeesfor Framing ofRules/Standards of food Articles

NationalMonitoringAgency forIrradiation ofFood

Coordinationwith NationalandInternationalOrganizations/ConsumerOrganizations/Industries

Central FoodLaboratories(4)

NationalCodexCommitteeand itsShadowCommittees

64

Regarding inspection and certifi cation procedures for imported food, Section 5 of the PFA Act, 1954, prohibits the import of the following articles of food:

Food which is adulterated.

Food which is misbranded.

Food which contravenes any other provision of the PFA Act or any Rule.

Th e important provisions which are required to be followed essentially while importing/clearing the food products are:

Authorized offi cers to check the imported food products.

Section 6 of the PFA Act, 1954, authorizes the custom collector to check the imported food prod-ucts.

Th e authorized offi cer, on suspicion, may detain any imported food product.

He will send the samples of the detained product to the Central Food Laboratory for analysis.

Imported food is inspected at the ports of entry by personnel of the Collectorate of Customs. If necessary, samples are further tested in the laboratories designated/notifi ed for this purpose by the Ministry of Health and Family Welfare to verify the compliance with the requirements stipulated under the PFA Act, 1954 and Rules.

With a view to streamline the checking of imported food products, the Government of India has issued various instructions from time-to-time. Various departments of the Government of India, including Health, Revenue, Commerce and the Directorate General of Foreign Trade, have initiated several steps to streamline the checking of imported food.

Regarding procedures for food export inspection and certifi cation, the Export Inspection Council (EIC) of the Ministry of Commerce and Industry is the offi cial government inspection body for certifying food products for export. It carries out the inspection of several food articles such as marine, milk products, meat, honey, poultry, Basmati rice, black pepper and cashew meant for export.

THE FOOD SAFETY AND STANDARDS BILL, 2005

Th e Ministry of Food Processing Industries has introduced “Th e Food Safety and Standards Bill, 2005” which seeks to consolidate the laws relating to food and establish the “Food Safety and Standards Authority of India”. Th is step has been taken keeping in view the fact that presently eight ministries are administering food laws in diverse ways which has been found to be not conducive to the growth of the food processing industry.

Th e proposed “Food Safety and Standards Authority of India” would facilitate scientifi c standards for food articles and regulate their manufacture, storage, distribution, sale and import to ensure the availability of safe and wholesome food for human consumption. Th e authority will consist of members from various ministries, and representatives from State Governments, the food industry, consumer organisations and even farmers’ organisations. Scientifi c committees and panels will assist it in fi xing standards, while a Central Advisory Committee will prioritise the work.

Th e enforcement of the legislation will be through the State Commissioner for Food Safety and Panchayati Raj/ municipal bodies. Th e Food Bill not only incorporates the salient provisions of the Prevention of Food Adulteration (PFA) Act, but is also based on international legislations, instrumentalities and Codex Alimentaries Commission (related to food safety norms).

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65

Th e proposed body will regulate the limits on the usage of food additives, crop contaminants, pesticide residues, heavy metals, processing aids, myco-toxins, antibiotics and pharmacological active substances.

It will formulate mechanisms and guidelines for the accreditation of bodies engaged in the certifi cation of a food safety management system for the food business. It will also set up food labelling standards, including claims on health, nutrition and special dietary uses. Th e Bill seeks to regulate nutraceuticals and dietary supplements. It has stressed on proper labelling and has said that information should not be misleading. Imposing restrictions on advertising, it specifi ed, “No advertisement shall be made of any food, which is misleading or contravenous to the provisions of this Act.” Th e Bill has imposed safeguards on imports of food products. No person shall be allowed to import unsafe, misbranded or sub-standard food and import-ing would require a licence. Stringent penalties have also been proposed in the Bill.

Th e Bill has also mooted the establishment of a Food Safety Appellate Tribunal to hear the appeals of disputed parties.

Th e “genetically modifi ed food” has been defi ned in the Bill as the food, which is produced through tech-niques in which the genetic material has been altered in a way that does not occur naturally by mating or having adequate human intervention or both. Techniques of Genetic Engineering or modifi cation include, but are not limited to recombinant DNA, cell fusion, micro and macro injection, encapsulation, gene deletion, addition and doubling.

Th ere is a provision for a separate scientifi c panel on genetically modifi ed organisms. As per the provisions of the Bill, no person shall manufacture, process, export, import or sell genetically modifi ed articles of food, organic foods, functional foods, neutraceuticals, health supplements etc. except in accordance with the regulations made-there for under this Act.

Various Acts/Orders which would stand repealed on commencement of this Act, include the Prevention of Food Adulteration and sections relating to food under the Environmental (Protection) Act, 1986 and the Environment Protection Rules, 1989.

Th e full text of the Food Safety and Standards Bill, 2005 can be accessed at http://www.mfpi.nic.in.

OVERVIEW OF MINISTRIES AND DEPARTMENTS INVOLVED IN REGULATION

OF GM FOOD

Several central ministries and departments are involved in India’s program of food quality and safety and hence each one of them has a role to play in the activities related to GM foods in India. Th ese include:

Ministry of Environment and Forest: Th is ministry holds the Secretariat of the Genetic Engineering Approval Committee, the apex body that gives approval for manufacture, sale, import and export of all GMOs and products thereof including foodstuff , ingredients in foodstuff and additives using genetically modifi ed (GM) organisms or cells.

Department of Biotechnology: Th is department holds the Secretariat of the Review Committee on Genetically Modifi cation that gives approval for research and small scale fi eld trials involving GMOs and products thereof. It also interacts with the Institutional Biosafety Committees (IBSCs) set up in all organizations undertaking activities involves GMOs.

Department of Health in the Ministry of Health and Family Welfare: Department of Health is responsible for implementation of the PFA Act under which the quality and safety of food is regulated. Th e Directorate General of Health Services has also been designed as the nodal Ministry with the Codex Alimentarious Commission.

1.

2.

3.

66

Th e Indian Council of Medical Research (ICMR) is the apex body in India for the formulation, coordination and promotion of biomedical research under the Ministry of Health and Family Welfare. ICMR acts as an advisory body for MoHFW on various issues including GM foods.

Ministry of Agriculture: Ministry of Agriculture is the nodal ministry for agriculture growth in the country. It comprises of three Departments viz. Department of Agriculture and Cooperation, Department of Agricultural Research & Education/ Indian Council of Agricultural Research (ICAR) and Department of Animal Husbandry & Dairying. Th e offi cials from ICAR and Ministry of Agriculture have an important role to play in the approval of GM crops as per Seed Policy, 2002.

Ministry of Commerce and Industry: Th is ministry is responsible for the formulation of the Export and Import (EXIM) Policy in the country. It implements a legislation prescribing a system of quality control and inspection for both export/import.

Ministry of Food Processing Industries: Th is ministry is responsible for the formulation of policy for the healthy growth of the food processing industries and provides developmental support to these industries. It encourages research and developmental activities and assists the industries in active participation in the laying down of food standards as well as their harmonization with inter-national standards. Th is ministry is also the licensing authority for processed fruits and vegetable industries.

Research Institutions:

National Institute of Nutrition (NIN), Hyderabad is India’s premier nutrition research institute working under the aegis of Indian Council of Medical Research (ICMR), Ministry of Health and Family Welfare, Government of India. ICMR proposes to set up a GM Food Safety Cell in NIN.

Central Food Technological Research Institute (CFTRI), Mysore is a premier institute working under Council of Scientifi c and Industrial Research. Its multi-disciplinary spread (across 16 R&D departments) covers almost every fi eld of scientifi c investigation connected with foods and their relationship to humans, including the cutting edge area of food biotechnology.

Th e Defence Food Research Laboratory (DFRL), Mysore under the aegis of Defence Research Development Organization (DRDO) caters to the varied food challenges for military and para-military forces. Th is laboratory is engaged in research & development of traditional indigenous foods and their preservation

Industrial Toxicology Research Center (ITRC), Lucknow a constituent laboratory of Council of Scientifi c & Industrial Research (CSIR) is dedicated to provide health safeguards to industrial and agricultural workers through its rich knowledgebase, created painstakingly over the years.

National Bureau of Plant Genetic Resources (NBPGR), New Delhi is the nodal organisation in India for collecting, introducing, evaluating and conserving plant genetic resources. NBPGR is also responsible for plant quarantine activities relating to exotic samples.

Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad is an autonomous institution supported by the DBT and is engaged in providing services for DNA fi ngerprinting and diagnostics in addition to basic research in related areas. DNA fi ngerprinting services are also being provided to various government and law enforcement agencies.

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67

STATUS OF DEVELOPMENT OF GM FOOD CROPS IN INDIA

Fourteen food crops have been approved for contained limited fi eld trials in India (Table 1). Th e trials are being conducted by both public and private sector institutions and the target traits include insect resistance, herbicide tolerance, viral and fungal disease resistance and stress tolerance.

Table 1: Transgenic crops under development and fi eld trials

Crop Organization GeneBrinjal IARI, New Delhi

MAHYCO, Mumbaicry1Abcry1Ac

Caulifl ower MAHYCO, MumbaiSungrow Seeds Ltd., New Delhi

cry1Accry1Ac

Cabbage Sungrow Seeds Ltd., New Delhi cry1AcChickpea ICRISAT, Hyderabad cry1Ac, cry1AbGroundnut ICRISAT, Hyderabad IPCVcp, IPCV replicase, Maize Monsanto, Mumbia CP4 EPSPSMustard IARI, New Delhi

NRCWS, JabalpurTERI, New DelhiUDSC, New Delhi

CodA, osmotinbar, barnase, barstarSsu-maize Psy, Ssu-tpCrtI bar, barnase , barstar

Okra MAHYCO, Mumbai cry1AcPigeonpea ICRISAT, Hyderabad

MAHYCO, Mumbaicry1Ab + SBTI cry1Ac

Potato CPRI, SimlaNCPGR, New Delhi

cry1AbAma-1

Rice Directorate of Rice Research, Hyderabad

Osmania University, HyderabadIARI, New Delhi

MAHYCO, MumbaiMKU, Madurai

MSSRF, ChennaiTNAU, Coimbatore

Bacterial blight resistant, Xa-21, cry1Ab, gna gene, sheath blight resistant gnaBt, chitinase, cry1Ac and cry1B-cry1Aa cry1Acchitinase, B-1,3-glucanase, osmo-tin genes from mangrove specieschitinase

Sorghum MAHYCO, Mumbai cry1AcTomato MAHYCO, Mumbai

NCPGRcry1AcOXDC

Source: Department of Biotechnology, Government of India

68

LABELLING ISSUES

India, along with a number of other countries, has supported the mandatory labeling of GM food by Codex.

Out of the two options under discussion by Codex i.e. Option 1 requires labeling when the products ob-tained through biotechnology diff er signifi cantly from the corresponding food as regards the composition, nutritional value or intended use and Option 2 require the declaration of the method of production for food and ingredients composed of or containing genetically modifi ed/engineered organisms and food or food ingredients produced from, but not containing, genetically modifi ed/engineered organisms if they contain protein or DNA resulting from gene technology or diff er signifi cantly from the corresponding food.

Th e labeling of food derived from biotechnology is a major issue for India as its delegation at the CCFL has been seeking to achieve mandatory labeling as set out in Option 2. However, Option 2 has also raised a number of issues of concern including the enforcement, methodology, economic cost, consumer perception and diffi culties likely to be faced.

69

SECTION 1 - INTRODUCTION

1. For many foods, the level of food safety generally accepted by the society reflects the history of their safe

consumption by humans. It is recognised that in many cases the knowledge required to manage the risks

associated with foods has been acquired in the course of their long history of use. Foods are generally

considered safe, provided that care is taken during development, primary production, processing, storage,

handling and preparation.

2. The hazards associated with foods are subjected to the risk analysis process of the Codex Alimentarius

Commission to assess potential risks and, if necessary, to develop approaches to manage these risks. The

conduct of risk analysis is guided by general decisions of the Codex Alimentarius Commission (CAC)1 as

well as the Codex Working Principles for Risk Analysis2.

3. While risk analysis has been used over a long period of time to address chemical hazards (e.g. residues of

pesticides, contaminants, food additives and processing aids), and it is being increasingly used to address

microbiological hazards and nutritional factors, the principles were not elaborated specifically for whole

foods.

4. The risk analysis approach can, in general terms, be applied to foods including foods derived from modern

biotechnology. However, it is recognised that this approach must be modified when applied to a whole

food rather than to a discrete hazard that may be present in food.

5. The principles presented in this document should be read in conjunction with the Codex Working

Principles for Risk Analysis to which these principles are supplemental.

6. Where appropriate, the results of a risk assessment undertaken by other regulatory authorities may be used

to assist in the risk analysis and avoid duplication of work.

SECTION 2 – SCOPE AND DEFINITIONS

7. The purpose of these Principles is to provide a framework for undertaking risk analysis on the safety and

nutritional aspects of foods derived from modern biotechnology. This document does not address

nvironmental, ethical, moral and socio-economic aspects of the research, development, production and

marketing of these foods 3.

8. The definitions below apply to these Principles:

“Modern Biotechnology” means the application of:

1 These decisions include the Statements of principle concerning the role of science in the Codex decision-making process and the extent to which other factors are taken into account and the Statements of principle relating to the role of food safety risk assessment (Codex Alimentarius Commission Procedural Manual; Thirteenth edition).

2 Adopted by the 26th Session of the Codex Alimentarius Commission, 2003

3 This document does not address animal feed and animals fed such feed except insofar as these animals have been

developed by using modern biotechnology.

Codex Alimentarius Principles for the Risk Analysis of Foods Derived from Modern

Biotechnology

70

Codex Alimentarius Foods derived from Biotechnology

(i) In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA) and direct

injection of nucleic acid into cells or organelles, or

(ii) Fusion of cells beyond the taxonomic family,

that overcome natural physiological reproductive or recombinant barriers and that are not techniques used

in traditional breeding and selection4.

“Conventional Counterpart ” means a related organism/variety, its components and/or products for

which there is experience of establishing safety based on common use as food5.

SECTION 3 – PRINCIPLES

9. The risk analysis process for foods derived from modern biotechnology should be consistent with the

Codex Working Principles for Risk Analysis.

RISK ASSESSMENT

10. Risk assessment includes a safety assessment, which is designed to identify whether a hazard, nutritional

or other safety concern is present, and if present, to gather information on its nature and severity. The

safety assessment should include a comparison between the food derived from modern biotechnology and

its conventional counterpart focusing on determination of similarities and differences. If a new or altered

hazard, nutritional or other safety concern is identified by the safety assessment, the risk associated with it

should be characterized to determine its relevance to human health.

11. A safety assessment is characterized by an assessment of a whole food or a component thereof relative to

the appropriate conventional counterpart:

a) taking into account both intended and unintended effects;

b) identifying new or altered hazards;

c) identifying changes, relevant to human health, in key nutrients.

12. A pre-market safety assessment should be undertaken following a structured and integrated approach and

be performed on a case-by-case basis. The data and information, based on sound science, obtained using

appropriate methods and analysed using appropriate statistical techniques, should be of a quality and, as

appropriate, of quantity that would withstand scientific peer review.

13. Risk assessment should apply to all relevant aspects of foods derived from modern biotechnology. The risk

assessment approach for these foods is based on a consideration of science-based multidisciplinary data

and information taking into account the factors mentioned in the accompanying Guidelines6.

14. Scientific data for risk assessment are generally obtained from a variety of sources, such as the developer

of the product, scientific literature, general technical information, independent scientists, regulatory

4 This definition is taken from the Cartagena Biosafety Protocol under the Convention on Biological Diversity.

5 It is recognized that for the foreseeable future, foods derived from modern biotechnology will not be used as

conventional counterparts.

6 Reference is made to the Guideline for the Conduct of Food Safety Assessment of Foods Derived from

Recombinant-DNA Plants and the Guideline for the Conduct of Food Safety Assessment of Foods Produced using

Recombinant-DNA Microorganisms.

71

Foods derived from Biotechnology Codex Alimentarius

agencies, international bodies and other interested parties. Data should be assessed using appropriate

science-based risk assessment methods.

15. Risk assessment should take into account all available scientific data and information derived from

different testing procedures, provided that the procedures are scientifically sound and the parameters being

measured are comparable.

RISK MANAGEMENT

16. Risk management measures for foods derived from modern biotechnology should be proportional to the

risk, based on the outcome of the risk assessment and, where relevant, taking into account other legitimate

factors in accordance with the general decisions of the Codex Alimentarius Commission (CAC)7 as well as

the Codex Working Principles for Risk Analysis.

17. It should be recognised that different risk management measures may be capable of achieving the same

level of protection with regard to the management of risks associated with safety and nutritional impacts

on human health, and therefore would be equivalent.

18. Risk managers should take into account the uncertainties identified in the risk assessment and implement

appropriate measures to manage these uncertainties.

19. Risk management measures may include, as appropriate, food labelling8, conditions for marketing

approvals and post-market monitoring.

20. Post-market monitoring may be an appropriate risk management measure in specific circumstances. Its

need and utility should be considered, on a case-by-case basis, during risk assessment and its practicability

should be considered during risk management. Post-market monitoring may be undertaken for the purpose

of:

A) verifying conclusions about the absence or the possible occurrence, impact and significance of

potential consumer health effects; and

B) monitoring changes in nutrient intake levels, associated with the introduction of foods likely to

significantly alter nutritional status, to determine their human health impact.

21. Specific tools may be needed to facilitate the implementation and enforcement of risk management

measures. These may include appropriate analytical methods; reference materials; and, the tracing of

products9 for the purpose of facilitating withdrawal from the market when a risk to human health has been

identified or to support post-market monitoring in circumstances as indicated in paragraph 20.

RISK COMMUNICATION

22. Effective risk communication is essential at all phases of risk assessment and risk management. It is an

interactive process involving all interested parties, including government, industry, academia, media and

consumers.

7 See footnote 1.

8 Reference is made to the Codex Committee on Food Labelling in relation to the Proposed Draft Guidelines for the

Labelling of Foods and Food Ingredients obtained through certain techniques of genetic modification/genetic

engineering at Step 3 of the procedures.

9 It is recognised that there are other applications of product tracing. These applications should be consistent with

the provisions of the SPS and TBT Agreements. The application of product tracing to the areas covered by both

Agreements is under consideration within Codex on the basis of decisions of 49th Session of Executive Committee.

72


23. Risk communication should include transparent safety assessment and risk management decision-making

processes. These processes should be fully documented at all stages and open to public scrutiny, whilst

respecting legitimate concerns to safeguard the confidentiality of commercial and industrial information.

In particular, reports prepared on the safety assessments and other aspects of the decision-making process

should be made available to all interested parties.

24. Effective risk communication should include responsive consultation processes. Consultation processes

should be interactive. The views of all interested parties should be sought and relevant food safety and

nutritional issues that are raised during consultation should be addressed during the risk analysis process.

CONSISTENCY

25. A consistent approach should be adopted to characterise and manage safety and nutritional risks associated

with foods derived from modern biotechnology. Unjustified differences in the level of risks presented to

consumers between these foods and similar conventional foods should be avoided.

26. A transparent and well-defined regulatory framework should be provided in characterising and managing

the risks associated with foods derived from modern biotechnology. This should include consistency of

data requirements, assessment frameworks, acceptable level of risk, communication and consultation

mechanisms and timely decision processes.

CAPACITY BUILDING AND INFORMATION EXCHANGE

27. Efforts should be made to improve the capability of regulatory authorities, particularly those of developing

countries, to assess, manage and communicate risks, including enforcement, associated with foods derived

from modern biotechnology or to interpret assessments undertaken by other authorities or recognised

expert bodies, including access to analytical technology. In addition capacity building for developing

countries either through bilateral arrangements or with assistance of international organizations should be

directed toward effective application of these principles10.

28. Regulatory authorities, international organisations and expert bodies and industry should facilitate through

appropriate contact points including but not limited to Codex Contact Points and other appropriate means,

the exchange of information including the information on analytical methods.

REVIEW PROCESSES

29. Risk analysis methodology and its application should be consistent with new scientific knowledge and

other information relevant to risk analysis.

30. Recognizing the rapid pace of development in the field of biotechnology, the approach to safety

assessments of foods derived from modern biotechnology should be reviewed when necessary to ensure

that emerging scientific information is incorporated into the risk analysis. When new scientific information

relevant to a risk assessment becomes available the assessment should be reviewed to incorporate that

information and, if necessary, risk management measures adapted accordingly.

10 Reference is made to technical assistance of provisions in Article 9 of the SPS Agreement and Article 11 of the TBT

Agreement.

73

SECTION 1 SCOPE-

1. This Guideline supports the Principles for the Risk Analysis of Foods Derived from Modern

Biotechnology. It addresses safety and nutritional aspects of foods consisting of, or derived from, plants

that have a history of safe use as sources of food, and that have been modified by modern biotechnology to

exhibit new or altered expression of traits.

2. This document does not address animal feed or animals fed with the feed. This document also does not

address environmental risks.

3. The Codex principles of risk analysis, particularly those for risk assessment, are primarily intended to

apply to discrete chemical entities such as food additives and pesticide residues, or a specific chemical or

microbial contaminant that have identifiable hazards and risks; they are not intended to apply to whole

foods as such. Indeed, few foods have been assessed scientifically in a manner that would fully

characterise all risks associated with the food. Further, many foods contain substances that would likely be

found harmful if subjected to conventional approaches to safety testing. Thus, a more focused approach is

required where the safety of a whole food is being considered.

4. This approach is based on the principle that the safety of foods derived from new plant varieties, including

recombinant-DNA plants, is assessed relative to the conventional counterpart having a history of safe use,

taking into account both intended and unintended effects. Rather than trying to identify every hazard

associated with a particular food, the intention is to identify new or altered hazards relative to the

conventional counterpart.

5. This safety assessment approach falls within the risk assessment framework as discussed in Section 3 of

the Principles for the Risk Analysis of Foods Derived from Modern Biotechnology. If a new or altered

hazard, nutritional or other food safety concern is identified by the safety assessment, the risk associated

with it would first be assessed to determine its relevance to human health. Following the safety assessment

and if necessary further risk assessment, the food would be subjected to risk management considerations in

accordance with the Principles for the Risk Analysis of Foods Derived from Modern Biotechnology before

it is considered for commercial distribution.

6. Risk management measures such as post-market monitoring of consumer health effects may assist the risk

assessment process. These are discussed in paragraph 20 of the Principles for the Risk Analysis of Foods

derived from Modern Biotechnology.

7. The Guideline describes the recommended approach to making safety assessments of foods derived from

recombinant-DNA plants where a conventional counterpart exists, and identifies the data and information

that are generally applicable to making such assessments. While this Guideline is designed for foods

derived from recombinant-DNA plants, the approach described could, in general, be applied to foods

derived from plants that have been altered by other techniques.

Codex Alimentarius Guideline for the Conduct of Food Safety Assessment of Foods Derived

from Recombinant DNA Plants

74


- I

-

SECTION 2 DEFINIT ONS

8. The definitions below apply to this Guideline:

“Recombinant-DNA Plant” - means a plant in which the genetic material has been changed through invitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA) and direct injection of

nucleic acid into cells or organelles.

“Conventional Counterpart” - means a related plant variety, its components and/or products for which

there is experience of establishing safety based on common use as food1.

SECTION 3 INTRODUCTION TO FOOD SAFETY ASSESSMENT

9. Traditionally, new varieties of food plants have not been systematically subjected to extensive chemical,

toxicological, or nutritional evaluation prior to marketing, with the exception of foods for specific groups,

such as infants, where the food may constitute a substantial portion of the diet. Thus, new varieties of corn,

soya, potatoes and other common food plants are evaluated by breeders for agronomic and phenotypic

characteristics, but generally, foods derived from such new plant varieties are not subjected to the rigorous

and extensive food safety testing procedures, including studies in animals, that are typical of chemicals

such as food additives or pesticide residues that may be present in food.

10. The use of animal models for assessing toxicological endpoints is a major element in the risk assessment of

many compounds such as pesticides. In most cases, however, the substance to be tested is well

characterised, of known purity, of no particular nutritional value, and, human exposure to it is generally

low. It is therefore relatively straightforward to feed such compounds to animals at a range of doses some

several orders of magnitude greater than the expected human exposure levels, in order to identify any

potential adverse health effects of importance to humans. In this way, it is possible, in most cases, to

estimate levels of exposure at which adverse effects are not observed and to set safe intake levels by the

application of appropriate safety factors.

11. Animal studies cannot readily be applied to testing the risks associated with whole foods, which are

complex mixtures of compounds, often characterised by a wide variation in composition and nutritional

value. Due to their bulk and effect on satiety, they can usually only be fed to animals at low multiples of the

amounts that might be present in the human diet. In addition, a key factor to consider in conducting animal

studies on foods is the nutritional value and balance of the diets used, in order to avoid the induction of

adverse effects which are not related directly to the material itself. Detecting any potential adverse effects

and relating these conclusively to an individual characteristic of the food can therefore be extremely

difficult. If the characterization of the food indicates that the available data are insufficient for a thorough

safety assessment, properly designed animal studies could be requested on the whole foods. Another

consideration in deciding the need for animal studies is whether it is appropriate to subject experimental

animals to such a study if it is unlikely to give rise to meaningful information.

1 It is recognized that for the foreseeable future, foods derived from modern biotechnology will not be used as

conventional counterparts.

75

Foods derived from Biotechnology Codex Alimentarius \

12. Due to the difficulties of applying traditional toxicological testing and risk assessment procedures to whole

foods, a more focused approach is required for the safety assessment of foods derived from food plants,

including recombinant-DNA plants. This has been addressed by the development of a multidisciplinary

approach for assessing safety which takes into account both intended and unintended changes that may

occur in the plant or in the foods derived from it, using the concept of substantial equivalence.13. The concept of substantial equivalence is a key step in the safety assessment process. However, it is not a

safety assessment in itself; rather it represents the starting point which is used to structure the safety

assessment of a new food relative to its conventional counterpart. This concept is used to identify

similarities and differences between the new food and its conventional counterpart2. It aids in the

identification of potential safety and nutritional issues and is considered the most appropriate strategy to

date for safety assessment of foods derived from recombinant-DNA plants. The safety assessment carried

out in this way does not imply absolute safety of the new product; rather, it focuses on assessing the safety

of any identified differences so that the safety of the new product can be considered relative to its

conventional counterpart.

UNINTENDED EFFECTS

14. In achieving the objective of conferring a specific target trait (intended effect) to a plant by the insertion of

defined DNA sequences, additional traits could, in some cases, be acquired or existing traits could be lost

or modified (unintended effects). The potential occurrence of unintended effects is not restricted to the use

of in vitro nucleic acid techniques. Rather, it is an inherent and general phenomenon that can also occur in

conventional breeding. Unintended effects may be deleterious, beneficial, or neutral with respect to the

health of the plant or the safety of foods derived from the plant. Unintended effects in recombinant-DNA

plants may also arise through the insertion of DNA sequences and/or they may arise through subsequent

conventional breeding of the recombinant-DNA plant. Safety assessment should include data and

information to reduce the possibility that a food derived from a recombinant-DNA plant would have an

unexpected, adverse effect on human health.

15. Unintended effects can result from the random insertion of DNA sequences into the plant genome which

may cause disruption or silencing of existing genes, activation of silent genes, or modifications in the

expression of existing genes. Unintended effects may also result in the formation of new or changed

patterns of metabolites. For example, the expression of enzymes at high levels may give rise to secondary

biochemical effects or changes in the regulation of metabolic pathways and/or altered levels of

metabolites.

16. Unintended effects due to genetic modification may be subdivided into two groups: those that are

"predictable" and those that are “unexpected”. Many unintended effects are largely predictable based on

knowledge of the inserted trait and its metabolic connections or of the site of insertion. Due to the

expanding information on plant genome and the increased specificity in terms of genetic materials

2 The concept of substantial equivalence as described in the report of the 2000 joint FAO /WHO expert

consultations (Document WHO/SDE/PHE/FOS/00.6, WHO, Geneva, 2000).

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introduced through recombinant-DNA techniques compared with other forms of plant breeding, it may

become easier to predict unintended effects of a particular modification. Molecular biological and

biochemical techniques can also be used to analyse potential changes at the level of gene transcription and

message translation that could lead to unintended effects.

17. The safety assessment of foods derived from recombinant-DNA plants involves methods to identify and

detect such unintended effects and procedures to evaluate their biological relevance and potential impact

on food safety. A variety of data and information are necessary to assess unintended effects because no

individual test can detect all possible unintended effects or identify, with certainty, those relevant to human

health. These data and information, when considered in total, provide assurance that the food is unlikely to

have an adverse effect on human health. The assessment for unintended effects takes into account the

agronomic/phenotypic characteristics of the plant that are typically observed by breeders in selecting new

varieties for commercialization. These observations by breeders provide a first screen for plants that

exhibit unintended traits. New varieties that pass this screen are subjected to safety assessment as

described in Sections 4 and 5.

FRAMEWORK OF FOOD SAFETY ASSESSMENT

18. The safety assessment of a food derived from a recombinant-DNA plant follows a stepwise process of

addressing relevant factors that include:

A) Description of the recombinant-DNA plant;

B) Description of the host plant and its use as food;

C) Description of the donor organism(s);

D) Description of the genetic modification(s);

E) Characterization of the genetic modification(s);

F) Safety assessment:

a) expressed substances (non-nucleic acid substances);

b) compositional analyses of key components;

c) evaluation of metabolites ;

d) food processing;

e) nutritional modification; and

G) Other considerations.

19. In certain cases, the characteristics of the product may necessitate development of additional data and

information to address issues that are unique to the product under review.

20. Experiments intended to develop data for safety assessments should be designed and conducted in

accordance with sound scientific concepts and principles, as well as, where appropriate, Good Laboratory

Practice. Primary data should be made available to regulatory authorities at request. Data should be

obtained using sound scientific methods and analysed using appropriate statistical techniques. The

sensitivity of all analytical methods should be documented.

21. The goal of each safety assessment is to provide assurance, in the light of the best available scientific

knowledge, that the food does not cause harm when prepared, used and/or eaten according to its intended

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use. The expected endpoint of such an assessment will be a conclusion regarding whether the new food is

as safe as the conventional counterpart taking into account dietary impact of any changes in nutritional

content or value. In essence, therefore, the outcome of the safety assessment process is to define the

product under consideration in such a way as to enable risk managers to determine whether any measures

are needed and if so to make well-informed and appropriate decisions.

-

-

( )

SECTION 4 GENERAL CONSIDERATIONS

DESCRIPTION OF THE RECOMBINANT DNA PLANT

22. A description of the recombinant-DNA plant being presented for safety assessment should be provided.

This description should identify the crop, the transformation event(s) to be reviewed and the type and

purpose of the modification. This description should be sufficient to aid in understanding the nature of the

food being submitted for safety assessment.

DESCRIPTION OF THE HOST PLANT AND ITS USE AS FOOD

23. A comprehensive description of the host plant should be provided. The necessary data and information

should include, but need not be restricted to:

A) common or usual name; scientific name; and, taxonomic classification;

B) history of cultivation and development through breeding, in particular identifying traits that may

adversely impact on human health ;

C) information on the host plant’s genotype and phenotype relevant to its safety, including any known

toxicity or allergenicity; and

D) history of safe use for consumption as food.

24. Relevant phenotypic information should be provided not only for the host plant, but also for related species

and for plants that have made or may make a significant contribution to the genetic background of the host

plant.

25. The history of use may include information on how the plant is typically cultivated, transported and stored,

whether special processing is required to make the plant safe to eat, and the plant’s normal role in the diet

(e.g. which part of the plant is used as a food source, whether its consumption is important in particular

subgroups of the population, what important macro- or micro-nutrients it contributes to the diet).

DESCRIPTION OF THE DONOR ORGANISM S

26. Information should be provided on the donor organism(s) and, when appropriate, on other related spieces.

It is particularly important to determine if the donor organism(s) or other closely related members of the

family naturally exhibit characteristics of pathogenicity or toxin production, or have other traits that affect

human health (e.g. presence of antinutrients). The description of the donor organism(s) should include:

A) its usual or common name;

B) scientific name;

C) taxonomic classification;

D) information about the natural history as concerns food safety;

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E) information on naturally occurring toxins, anti-nutrients and allergens; for microorganisms,

additional information on pathogenicity and the relationship to known pathogens; and

F) information on the past and present use, if any, in the food supply and exposure route(s) other than

intended food use (e.g. possible presence as contaminants).

(

(

DESCRIPTION OF THE GENETIC MODIFICATION S)

27. Sufficient information should be provided on the genetic modification to allow for the identification of all

genetic material potentially delivered to the host plant and to provide the necessary information for the

analysis of the data supporting the characterization of the DNA inserted in the plant.

28. The description of the transformation process should include:

A) information on the specific method used for the transformation (e.g. Agrobacterium-mediated

transformation);

B) information, if applicable, on the DNA used to modify the plant (e.g. helper plasmids), including the

source (e.g. plant, microbial, viral , synthetic), identity and expected function in the plant; and

C) intermediate host organisms including the organisms (e.g. bacteria) used to produce or process DNA

for transformation of the host organism;

29. Information should be provided on the DNA to be introduced, including:

A) the characterization of all the genetic components including marker genes, regulatory and other

elements affecting the function of the DNA;

B) the size and identity;

C) the location and orientation of the sequence in the final vector/construct; and

D) the function.

CHARACTERIZATION OF THE GENETIC MODIFICATION S)

30. In order to provide clear understanding of the impact on the composition and safety of foods derived from

recombinant-DNA plants, a comprehensive molecular and biochemical characterization of the genetic

modification should be carried out.

31. Information should be provided on the DNA insertions into the plant genome; this should include:

A) the characterization and description of the inserted genetic materials;

B) the number of insertion sites;

C) the organisation of the inserted genetic material at each insertion site including copy number and

sequence data of the inserted material and of the surrounding region, sufficient to identify any

substances expressed as a consequence of the inserted material, or, where more appropriate, other

information such as analysis of transcripts or expression products to identify any new substances

that may be present in the food; and

D) identification of any open reading frames within the inserted DNA or created by the insertions with

contiguous plant genomic DNA including those that could result in fusion proteins.

32. Information should be provided on any expressed substances in the recombinant-DNA plant; this should

include:

A) the gene product(s) (e.g. a protein or an untranslated RNA);

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B) the gene product(s)’ function;

C) the phenotypic description of the new trait(s);

D) the level and site of expression in the plant of the expressed gene product(s), and the levels of its

metabolites in the plant, particularly in the edible portions; and

E) where possible, the amount of the target gene product(s) if the function of the expressed

sequence(s)/gene(s) is to alter the accumulation of a specific endogenous mRNA or protein.

33. In addition, information should be provided:

A) to demonstrate whether the arrangement of the genetic material used for insertion has been

conserved or whether significant rearrangements have occurred upon integration;

B) to demonstrate whether deliberate modifications made to the amino acid sequence of the expressed

protein result in changes in its post-translational modification or affect sites critical for its structure

or function;

C) to demonstrate whether the intended effect of the modification has been achieved and that all

expressed traits are expressed and inherited in a manner that is stable through several generations

consistent with laws of inheritance. It may be necessary to examine the inheritance of the DNA

insert itself or the expression of the corresponding RNA if the phenotypic characteristics cannot be

measured directly;

D) to demonstrate whether the newly expressed trait(s) are expressed as expected in the appropriate

tissues in a manner and at levels that are consistent with the associated regulatory sequences driving

the expression of the corresponding gene;

E) to indicate whether there is any evidence to suggest that one or several genes in the host plant has

been affected by the transformation process; and

F) to confirm the identity and expression pattern of any new fusion proteins.

SAFETY ASSESSMENT

Expressed Substances (non-nucleic acid substances)

Assessment of possible toxicity

34. In vitro nucleic acid techniques enable the introduction of DNA that can result in the synthesis of new

substances in plants. The new substances can be conventional components of plant foods such as proteins,

fats, carbohydrates, vitamins which are novel in the context of that recombinant-DNA plant. New

substances might also include new metabolites resulting from the activity of enzymes generated by the

expression of the introduced DNA.

35. The safety assessment should take into account the chemical nature and function of the newly expressed

substance and identify the concentration of the substance in the edible parts of the recombinant-DNA

plant, including variations and mean values. Current dietary exposure and possible effects on population

sub-groups should also be considered.

36. Information should be provided to ensure that genes coding for known toxins or anti-nutrients present in

the donor organisms are not transferred to recombinant-DNA plants that do not normally express those

toxic or anti-nutritious characteristics. This assurance is particularly important in cases where a

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recombinant-DNA plant is processed differently from a donor plant, since conventional food processing

techniques associated with the donor organisms may deactivate, degrade or eliminate anti-nutrients or

toxicants.

37. For the reasons described in Section 3, conventional toxicology studies may not be considered necessary

where the substance or a closely related substance has, taking into account its function and exposure, been

consumed safely in food. In other cases, the use of appropriate conventional toxicology or other studies on

the new substance may be necessary.

38. In the case of proteins, the assessment of potential toxicity should focus on amino acid sequence similarity

between the protein and known protein toxins and anti-nutrients (e.g. protease inhibitors, lectins) as well as

stability to heat or processing and to degradation in appropriate representative gastric and intestinal model

systems. Appropriate oral toxicity studies3 may need to be carried out in cases where the protein present in

the food is not similar to proteins that have previously been consumed safely in food, and taking into

account its biological function in the plant where known.

39. Potential toxicity of non-protein substances that have not been safely consumed in food should be assessed

on a case-by-case basis depending on the identity and biological function in the plant of the substance and

dietary exposure. The type of studies to be performed may include studies on metabolism, toxicokinetics,

sub-chronic toxicity, chronic toxicity/carcinogenicity, reproduction and development toxicity according to

the traditional toxicological approach.

40. This may require the isolation of the new substance from the recombinant-DNA plant, or the synthesis or

production of the substance from an alternative source, in which case, the material should be shown to be

biochemically, structurally, and functionally equivalent to that produced in the recombinant-DNA plant.

Assessment of possible allergenicity (proteins)

41. When the protein(s) resulting from the inserted gene is present in the food, it should be assessed for

potential allergenicity in all cases. An integrated, stepwise, case-by-case approach used in the assessment

of the potential allergenicity of the newly-expressed protein(s) should rely upon various criteria used in

combination (since no single criterion is sufficiently predictive on either allergenicity or

non-allergenicity). As noted in paragraph 20, the data should be obtained using sound scientific methods.

A detailed presentation of issues to be considered can be found in the Annex to this document. 4

42. The newly expressed proteins in foods derived from recombinant-DNA plants should be evaluated for any

possible role in the elicitation of gluten-sensitive enteropathy, if the introduced genetic material is obtained

from wheat, rye, barley, oats, or related cereal grains.

3 Guidelines for oral toxicity studies have been developed in international fora, for example, the OECD Guidelines

for the Testing of Chemicals..

4 The FAO/WHO expert consultation 2001 report , which includes reference to several decision trees, was used in

developing the Annex to these guidelines.

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43. The transfer of genes from commonly allergenic foods and from foods known to elicit gluten-sensitive

enteropathy in sensitive individuals should be avoided unless it is documented that the transferred gene

does not code for an allergen or for a protein involved in gluten-sensitive enteropathy.

Compositional Analyses of Key Components

44. Analyses of concentrations of key components5 of the recombinant-DNA plant and, especially those

typical of the food, should be compared with an equivalent analysis of a conventional counterpart grown

and harvested under the same conditions. In some cases, a further comparison with the recombinant-DNA

plant grown under its expected agronomic conditions may need to be considered (e.g. application of an

herbicide). The statistical significance of any observed differences should be assessed in the context of the

range of natural variations for that parameter to determine its biological significance. The comparator(s)

used in this assessment should ideally be the near isogenic parental line. In practice, this may not be

feasible at all times, in which case a line as close as possible should be chosen. The purpose of this

comparison, in conjunction with an exposure assessment as necessary, is to establish that substances that

are nutritionally important or that can affect the safety of the food have not been altered in a manner that

would have an adverse impact on human health.

45. The location of trial sites should be representative of the range of environmental conditions under which

the plant varieties would be expected to be grown. The number of trial sites should be sufficient to allow

accurate assessment of compositional characteristics over this range. Similarly, trials should be conducted

over a sufficient number of generations to allow adequate exposure to the variety of conditions met in

nature. To minimise environmental effects, and to reduce any effect from naturally occurring genotypic

variation within a crop variety, each trial site should be replicated. An adequate number of plants should

be sampled and the methods of analysis should be sufficiently sensitive and specific to detect variations in

key components.

Evaluation of Metabolites

46. Some recombinant-DNA plants may have been modified in a manner that could result in new or altered

levels of various metabolites in the food. Consideration should be given to the potential for the

accumulation of metabolites in the food that would adversely affect human health. Safety assessment of

such plants requires investigation of residue and metabolite levels in the food and assessment of any

alterations in nutrient profile. Where altered residue or metabolite levels are identified in foods,

consideration should be given to the potential impacts on human health using conventional procedures for

establishing the safety of such metabolites (e.g. procedures for assessing the human safety of chemicals in

foods).

5 Key nutrients or key anti-nutrients are those components in a particular food that may have a substantial impact in

the overall diet. They may be major constituents (fats, proteins, carbohydrates as nutrients or enzyme inhibitors as

anti-nutrients) or minor compounds (minerals, vitamins). Key toxicants are those toxicologically significant

compounds known to be inherently present in the plant, such as those compounds whose toxic potency and level

may be significant to health (e.g. solanine in potatoes if the level is increased, selenium in wheat) and allergens.

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Food Processing

47. The potential effects of food processing, including home preparation, on foods derived from

recombinant-DNA plants should also be considered. For example, alterations could occur in the heat

stability of an endogenous toxicant or the bioavailability of an important nutrient after processing.

Information should therefore be provided describing the processing conditions used in the production of a

food ingredient from the plant. For example, in the case of vegetable oil, information should be provided

on the extraction process and any subsequent refining steps.

Nutritional Modification

48. The assessment of possible compositional changes to key nutrients, which should be conducted for all

recombinant-DNA plants, has already been addressed under ‘Compositional analyses of key components’.

However, foods derived from recombinant-DNA plants that have undergone modification to intentionally

alter nutritional quality or functionality should be subjected to additional nutritional assessment to assess

the consequences of the changes and whether the nutrient intakes are likely to be altered by the

introduction of such foods into the food supply.

49. Information about the known patterns of use and consumption of a food, and its derivatives should be used

to estimate the likely intake of the food derived from the recombinant-DNA plant. The expected intake of

the food should be used to assess the nutritional implications of the altered nutrient profile both at

customary and maximal levels of consumption. Basing the estimate on the highest likely consumption

provides assurance that the potential for any undesirable nutritional effects will be detected. Attention

should be paid to the particular physiological characteristics and metabolic requirements of specific

population groups such as infants, children, pregnant and lactating women, the elderly and those with

chronic diseases or compromised immune systems. Based on the analysis of nutritional impacts and the

dietary needs of specific population subgroups, additional nutritional assessments may be necessary. It is

also important to ascertain to what extent the modified nutrient is bioavailable and remains stable with

time, processing and storage.

50. The use of plant breeding, including in vitro nucleic acid techniques, to change nutrient levels in crops can

result in broad changes to the nutrient profile in two ways. The intended modification in plant constituents

could change the overall nutrient profile of the plant product and this change could affect the nutritional

status of individuals consuming the food. Unexpected alterations in nutrients could have the same effect.

Although the recombinant-DNA plant components may be individually assessed as safe, the impact of the

change on the overall nutrient profile should be determined.

51. When the modification results in a food product, such as vegetable oil, with a composition that is

significantly different from its conventional counterpart, it may be appropriate to use additional

conventional foods or food components (i.e. foods or food components whose nutritional composition is

closer to that of the food derived from recombinant-DNA plant) as appropriate comparators to assess the

nutritional impact of the food.

52. Because of geographical and cultural variation in food consumption patterns, nutritional changes to a

specific food may have a greater impact in some geographical areas or in some cultural population than in

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others. Some food plants serve as the major source of a particular nutrient in some populations. The

nutrient and the populations affected should be identified.

53. Some foods may require additional testing. For example, animal feeding studies may be warranted for

foods derived from recombinant-DNA plants if changes in the bioavailability of nutrients are expected or

if the composition is not comparable to conventional foods. Also, foods designed for health benefits may

require specific nutritional, toxicological or other appropriate studies. If the characterization of the food

indicates that the available data are insufficient for a thorough safety assessment, properly designed animal

studies could be requested on the whole foods.

SECTION 5 – OTHER CONSIDERATIONS

POTENTIAL ACCUMULATION OF SUBSTANCES SIGNIFICANT TO HUMAN HEALTH

54. Some recombinant-DNA plants may exhibit traits (e.g., herbicide tolerance) which may indirectly result in

the potential for accumulation of pesticide residues, altered metabolites of such residues, toxic

metabolites, contaminants , or other substances which may be relevant to human health. The safety

assessment should take this potential for accumulation into account. Conventional procedures for

establishing the safety of such compounds (e.g., procedures for assessing the human safety of chemicals)

should be applied.

USE OF ANTIBIOTIC RESISTANCE MARKER GENES

55. Alternative transformation technologies that do not result in antibiotic resistance marker genes in foods

should be used in the future development of recombinant-DNA plants, where such technologies are

available and demonstrated to be safe.

56. Gene transfer from plants and their food products to gut microorganisms or human cells is considered a rare

possibility because of the many complex and unlikely events that would need to occur consecutively.

Nevertheless, the possibility of such events cannot be completely discounted6.

57. In assessing safety of foods containing antibiotic resistance marker genes, the following factors should be

considered:

A) the clinical and veterinary use and importance of the antibiotic in question;

(Certain antibiotics are the only drug available to treat some clinical conditions (e.g. vancomycin for

use in treating certain staphylococcal infections). Marker genes encoding resistance to such antibiotics

should not be used in recombinant-DNA plants.)

B) whether the presence in food of the enzyme or protein encoded by the antibiotic resistance marker

gene would compromise the therapeutic efficacy of the orally administered antibiotic; and

(This assessment should provide an estimate of the amount of orally ingested antibiotic that could be

degraded by the presence of the enzyme in food, taking into account factors such as dosage of the

6 In cases where there are high levels of naturally occurring bacteria which are resistant to the antibiotic, the

likelihood of such bacteria transferring this resistance to other bacteria will be orders of magnitude higher than the

likelihood of transfer between ingested foods and bacteria.

84


antibiotic, amount of enzyme likely to remain in food following exposure to digestive conditions,

including neutral or alkaline stomach conditions and the need for enzyme cofactors (e.g. ATP) for

enzymatic activity and estimated concentration of such factors in food.)

C) safety of the gene product, as would be the case for any other expressed gene product.

58. If evaluation of the data and information suggests that the presence of the antibiotic resistance marker gene

or gene product presents risks to human health, the marker gene or gene product should not be present in

the food. Antibiotic resistance genes used in food production that encode resistance to clinically used

antibiotics should not be present in foods.

REVIEW OF SAFETY ASSESSMENTS

59. The goal of the safety assessment is a conclusion as to whether the new food is as safe as the conventional

counterpart taking into account dietary impact of any changes in nutritional content or value. Nevertheless,

the safety assessment should be reviewed in the light of new scientific information that calls into question

the conclusions of the original safety assessment.

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Annex

Assessment of Possible Allergenicity

Section 1 – Introduction

�� All newly expressed proteins1 in recombinant-DNA plants that could be present in the final food

should be assessed for their potential to cause allergic reactions. This should include consideration

of whether a newly expressed protein is one to which certain individuals may already be sensitive as

well as whether a protein new to the food supply is likely to induce allergic reactions in some

individuals.

2. At present, there is no definitive test that can be relied upon to predict allergic response in humans to

a newly expressed protein, therefore, it is recommended that an integrated, stepwise, case by case

approach, as described below, be used in the assessment of possible allergenicity of newly

expressed proteins. This approach takes into account the evidence derived from several types of

information and data since no single criterion is sufficiently predictive.

3. The endpoint of the assessment is a conclusion as to the likelihood of the protein being a food

allergen.

Section 2 - Assessment Strategy

4. The initial steps in assessing possible allergenicity of any newly expressed proteins are the

determination of: the source of the introduced protein; any significant similarity between the amino

acid sequence of the protein and that of known allergens; and its structural properties, including but

not limited to, its susceptibility to enzymatic degradation, heat stability and/or, acid and enzymatic

treatment.

5. As there is no single test that can predict the likely human IgE response to oral exposure, the first

step to characterize newly expressed proteins should be the comparison of the amino acid sequence

and certain physicochemical characteristics of the newly expressed protein with those of established

allergens in a weight of evidence approach. This will require the isolation of any newly expressed

proteins from the recombinant-DNA plant, or the synthesis or production of the substance from an

alternative source, in which case the material should be shown to be structurally, functionally and

biochemically equivalent to that produced in the recombinant-DNA plant. Particular attention

should be given to the choice of the expression host, since post-translational modifications allowed

by different hosts (i.e.: eukaryotic vs. prokaryotic systems) may have an impact on the allergenic

1 This assessment strategy is not applicable for assessing whether newly expressed proteins are capable of inducing

gluten-sensitive or other enteropathies. The issue of enteropathies is already addressed in Assessment of possible

allergenicity (proteins), paragraph 42 of the Guideline for the Conduct of Food Safety Assessment of Foods Derived from

Recombinant-DNA Plants. In addition, the strategy is not applicable to the evaluation of foods where gene products are

down regulated for hypoallergenic purposes.

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Foods derived from Biotechnology C odex Alimentarius

potential of the protein.

6. It is important to establish whether the source is known to cause allergic reactions. Genes derived

from known allergenic sources should be assumed to encode an allergen unless scientific

evidence demonstrates otherwise.

Section 3 – Initial Assessment

Section 3.1 - Source of the Protein

7. As part of the data supporting the safety of foods derived from recombinant-DNA plants,

information should describe any reports of allergenicity associated with the donor organism.

Allergenic sources of genes would be defined as those organisms for which reasonable evidence

of IgE mediated oral, respiratory or contact allergy is available. Knowledge of the source of the

introduced protein allows the identification of tools and relevant data to be considered in the

allergenicity assessment. These include: the availability of sera for screening purposes;

documented type, severity and frequency of allergic reactions; structural characteristics and

amino acid sequence; physicochemical and immunological properties (when available) of

known allergenic proteins from that source.

Section 3.2 – Amino Acid Sequence Homology

8. The purpose of a sequence homology comparison is to assess the extent to which a newly expressed

protein is similar in structure to a known allergen. This information may suggest whether that

protein has an allergenic potential. Sequence homology searches comparing the structure of all

newly expressed proteins with all known allergens should be done. Searches should be conducted

using various algorithms such as FASTA or BLASTP to predict overall structural similarities.

Strategies such as stepwise contiguous identical amino acid segment searches may also be

performed for identifying sequences that may represent linear epitopes. The size of the contiguous

amino acid search should be based on a scientifically justified rationale in order to minimize the

potential for false negative or false positive results2. Validated search and evaluation procedures

should be used in order to produce biologically meaningful results.

9. IgE cross-reactivity between the newly expressed protein and a known allergen should be

considered a possibility when there is more than 35% identity in a segment of 80 or more amino

acids (FAO/WHO 2001) or other scientifically justified criteria. All the information resulting from

the sequence homology comparison between the newly expressed protein and known allergens

should be reported to allow a case-by-case scientifically based evaluation.

2 It is recognized that the 2001 FAO/WHO consultation suggested moving from 8 to 6 identical amino acid segments in

searches. The smaller the peptide sequence used in the stepwise comparison, the greater the likelihood of identifying false

87


10. Sequence homology searches have certain limitations. In particular, comparisons are limited to the

sequences of known allergens in publicly available databases and the scientific literature. There are

also limitations in the ability of such comparisons to detect non-contiguous epitopes capable of

binding themselves specifically with IgE antibodies.

11. A negative sequence homology result indicates that a newly expressed protein is not a known

allergen and is unlikely to be cross-reactive to known allergens. A result indicating absence of

significant sequence homology should be considered along with the other data outlined under this

strategy in assessing the allergenic potential of newly expressed proteins. Further studies should be

conducted as appropriate (see also sections 4 and 5). A positive sequence homology result indicates

that the newly expressed protein is likely to be allergenic. If the product is to be considered further,

it should be assessed using serum from individuals sensitized to the identified allergenic source.

Section 3.3 – Pepsin Resistance

12. Resistance to pepsin digestion has been observed in several food allergens; thus a correlation

exists between resistance to digestion by pepsin and allergenic potential3. Therefore, the

resistance of a protein to degradation in the presence of pepsin under appropriate conditions

indicates that further analysis should be conducted to determine the likelihood of the newly

expressed protein being allergenic. The establishment of a consistent and well-validated pepsin

degradation protocol may enhance the utility of this method. However, it should be taken into

account that a lack of resistance to pepsin does not exclude that the newly expressed protein can

be a relevant allergen.

13. Although the pepsin resistance protocol is strongly recommended, it is recognized that other

enzyme susceptibility protocols exist. Alternative protocols may be used where adequate

justification is provided4.

Section 4 – Specific Serum Screening

14. For those proteins that originate from a source known to be allergenic, or have sequence homology

with a known allergen, testing in immunological assays should be performed where sera are

available. Sera from individuals with a clinically validated allergy to the source of the protein can be

used to test the specific binding to IgE class antibodies of the protein in in vitro assays. A critical

positives, inversely, the larger the peptide sequence used, the greater the likelihood of false negatives, thereby reducing

the utility of the comparison. 3 The method outlined in the U.S. Pharmacopoeia (1995) was used in the establishment of the correlation (Astwood et al.

1996). 4 Report of Joint FAO/WHO Expert Consultation on Allergenicity of Foods Derived from Biotechnology (2001): Section

"6.4 Pepsin Resistance"

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Foods derived from Biotechnology C odex Alimentarius

issue for testing will be the availability of human sera from sufficient numbers of individuals5. In

addition, the quality of the sera and the assay procedure need to be standardized to produce a valid

test result. For proteins from sources not known to be allergenic, and which do not exhibit sequence

homology to a known allergen, targeted serum screening may be considered where such tests are

available as described in paragraph 17.

15. In the case of a newly expressed protein derived from a known allergenic source, a negative result in

in vitro immunoassays may not be considered sufficient, but should prompt additional testing, such

as the possible use of skin test and ex vivo protocols6. A positive result in such tests would indicate a

potential allergen.

Section 5 – Other Considerations

16. The absolute exposure to the newly expressed protein and the effects of relevant food processing will

contribute toward an overall conclusion about the potential for human health risk. In this regard, the

nature of the food product intended for consumption should be taken into consideration in

determining the types of processing which would be applied and its effects on the presence of the

protein in the final food product.

17. As scientific knowledge and technology evolves, other methods and tools may be considered in

assessing the allergenicity potential of newly expressed proteins as part of the assessment strategy.

These methods should be scientifically sound and may include targeted serum screening (i.e. the

assessment of binding to IgE in sera of individuals with clinically validated allergic responses to

broadly-related categories of foods); the development of international serum banks; use of animal

models; and examination of newly expressed proteins for T-cell epitopes and structural motifs

associated with allergens.

5 According to the Joint Report of the FAO/WHO Expert Consultation on Allergenicity of Foods Derived from

Biotechnology (22-25 January 2001, Rome, Italy) a minimum of 8 relevant sera is required to achieve a 99% certainty that

the new protein is not an allergen in the case of a major allergen. Similarly, a minimum of 24 relevant sera is required to

achieve the same level of certainty in the case of a minor allergen. It is recognized that these quantities of sera may not be

available for testing purposes. 6 Ex vivo procedure is described as the testing for allergenicity using cells or tissue culture from allergic human subjects

(Report of Joint FAO/WHO Expert Consultation on Allergenicity of Foods derived from Biotechnology )

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