GM FOOD COMPOSITION FW Jansen van Rijssen PhD GMASSURE GM Food Safety Training 23 – 25 Nov 2015 Cottonseed oil from GMO cotton? 4 Why compositional analysis of conventional crops? • Voluntary – Trading – Environmental impact – Biological variation as benchmarks • Regulatory – Variety registration – Labeling (Codex Alimentarius) – Food safety • Research Conventional methods: • COMPOSITIONAL ANALYSIS – Concentration of components (nutrients, antinutrients, toxicants) and more recently more awareness of allergens • NUTRITIONAL ASSESSMENT – In vitro assays (digestibility) – Wholesomeness – nutritive value and performance. Tendency for more detailed information SEED DEVELOPMENT • Molecular Biology • Genome plasticity AGRONOMIC AND PHENOTYPE ASSESSMENT • Comparative analysis • familiarity FOOD ANALYSIS • Codex Alimentarius • OECD PROBLEM FORMULATION FOOD ANALYSIS INTENDED/ UNINTENDED EFFECTS ? FOOD COMPOSITION -SAFETY ASSESSMENT OF GM FOODS • FAO/WHO Codex Alimentarius Commission ad hoc committee (1990 , 1996, 2000), • OECD 1993 onwards Test • Critical compositional elements of the modified variety Comparator • Non-GM variety with history of safe use • Near isogenic line grown under identical conditions. References • Conventional varieties or hybrids that are grown commercially in the geographies of the field trials. Comparative approach • Most appropriate strategy for the safety / nutritional assessment of GM-food • Focus on determination of similarities and differences between GM-food and conventional counterparts • Not a safety assessment in itself but a key step in the process of safety assessment COMPOSITION ANALYSIS (EFSA, 2008) CODEX ALIMENTARIUS WORKING PRINCIPLES FOR RISK ANALYSIS TRANSGENES/GMO COMPARATIVE APPROACH • • • • • TARGETED APPROACH Near(est) iso-line Critical components Characteristics of the crop History of safe use Safety assessment HISTORY OF SAFE USE • The USA Food and Drug Administration (USFDA): “generally recognized as safe” (GRAS) ‒ for food or food additives, which includes a long history of use or by virtue of scientific information about the nature of the substances, their customary or projected conditions of use, and the information generally available to scientists about the substances . HISTORY OF SAFE USE • The Organization for Economic Co-operation and Development (OECD) accepts that a “long history of use is a reassuring and practical starting point” for evaluating the safety of GM food and has prepared a number of guidelines in this respect. History of Safe Use (Constable et al 2007) • History: Correct identification; Biology (origin, genetic diversity); Length of use; Geographic/demographic distribution of use; Details of use; Evidence of adverse effects; Reliability of data • Safe: Composition (especially toxic, allergenic, metabolic, nutritional and antinutritional components as well as health compromising compounds). In silico tests (e.g. structural homology to known allergens or known toxins); In vitro tests (e.g. serum screening, digestibility tests); Animal studies (toxicology and nutrition studies); Experience from human exposure; Clinical studies; Epidemiological evidence. • Use: Type/purpose (e.g. as a food, ingredient, supplement or pharmaceutical). Safety: • “..it is a judgment, it is value laden… ..understood within contexts of society, culture, politics , and economics’ (Wolt, 2008) • Reasonable certainty of no harm (OECD, 1993) Risk: • “ ..there is always a degree of risk..” (Wolt, 2008; Querci et al., 2010) “History of safe use” of CASSAVA Containing CYANOGENIC GLYCOSIDES ? CYANOGENIC GLYCOSIDES (addendum) CONSENSUS DOCUMENTS Contents of consensus document • • • • • • • • • • • • • • • • • • • ABOUT THE OECD FOREWORD PREAMBLE THE ROLE OF COMPARATIVE APPROACH AS PART OF A SAFETY ASSESSMENT ACRONYMS SECTION I –BACKGROUND 1. General description of cassava 2. Production ..... 3. Processing and Use 3.1 General human and animal consumption 3.2 Human food processing 3.3 Animal feed processing 3.4 Range of industrial food products 3.5 Ethanol production and animal feed by‐ products 4. Appropriate comparators for testing new varieties 5. Breeding characteristics screened by developers .. SECTION II –NUTRIENT 1. Unprocessed roots and leaves . 1.1 Proximate composition Contents of consensus document • • • • • • • • • • • • • • • • • • • • 1.2 Carbohydrates 1.3 True protein (amino acids) 1.4 Lipids 1.5 Minerals 1.6 Vitamins 2. Processed cassava products SECTION III –OTHE CONSTITUENTS R 1. Anti‐nutrients 1.1 Tannins 1.2 Phytic Acid 1.3 Oxalate, Nitrate, Polyphenol, Saponin, Trypsin inhibitor 2. Toxicants 3. Allergens . SECTION IV‐ SUGGESTED CONSTITUENTS TO BE ANALYZED RELATED TO FOOD USE 1. Food uses and products 2. Suggested analysis for food use SECTION V ‐ SUGGESTED CONSTITUENTS TO BE ANALYZED RELATED TO FEED USE 1. Livestock feed uses 2. Suggested analysis for feed use SECTION VI – REFERENCES Food constituents to be analysed in fresh roots and leaves of cassava (OECD, 2009) Constituent/analytes Proximate Fresh leaves Fresh roots X X Starch X Fatty acids X X Amino acids X X Mineral X Vitamins X X Cyanogenic glycosides (linamarin and lotaustralin) X X HCN X X Tannins X Phytic acid X FOCUSSED APPROACH “SEARCH LIGHT” X Feed constituents to be analysed in fresh roots and leaves of cassava for f(OECD, 2009) Constituent/analytes Proximate Fresh leaves Fresh roots X X Starch X Acid detergent fibre X X Neutral detergent fibre X X Calcium X Phosphorous X Cyanogenic glycosides (linamarin and lotaustralin) X Tannins X Phytic acid X X VARIATION OF NUTRIENT CONTENTS IN FOODS (INFOODS) Nutrient contents in foods can vary significantly because of: environmental, genetic and processing influences such as feed, soil, climate, genetic resources (varieties/cultivars, breeds), storage conditions, processing, fortification and market share; Distribution of Maize Protein Values in ILSI Database Distribution of Protein Values in ILSI Database 50 45 Number of Samples 40 35 Argentina EU 30 United States 25 20 15 10 5 0 5 7 9 11 Protein (% dw) 13 15 17 Natural Variability – Conventional Maize Hybrids 30 7 Varieties, 6 Locations, 1 Year 25 20 15 10 5 0 Asp Thr Ser Glu Pro Gly Ala Cys Val Met Iso Leu Tyr Phe His Lys Arg Trp Amino acids (Reynolds et al., 2005). Changes within this range are normal (and safe) Isoflavones in soybean Are physiologically active Variety Place mg isoflavones/10 g Hardin Hardin Hardin Hardin Girard, IL Urbana, IL Pontiac, IL Dekalb, IL 47 a 82 a 156 b 171 b Hardin Amcor Century Sprite Urbana, IL Urbana, IL Urbana, IL Urbana, IL 116 150 250 309 a b c d Parrot - OMIC: Metabolic Pathways Number of publications comparing GM and non-GM crop varieties with or without intentional metabolic changes (Ricroch et al., 2011) Number of crop plants Metabolic changes Not metabolic changes 10 25 19 • Natural variation explain most transcriptomic changes among maize plants.... (Coll et al., 2010) • Gene expression profiles of GM.... Comparable with nonGM...” (Coll et al., 2009) • Micro-array analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion (Batista et al., 2008) • Transgenesis has less impact on the transcriptome of wheat grain than conventional breeding (Baudo, 2006) • Global transcriptome profiling is a poor predictor of the secondary effects of transgene influencing abiotic stress tolerance (Chan et al., 2012) Increased safety assessment? Single traits Stacked traits ? Comparative approach Compositional assessment Metabolic pathways Metabolic pathways Nutritionally enhanced / abiotic stress Comparative approach Compositional assessment PLACE FOR / OF OMICS - STUDIES ? Metabolic pathways Metabolic pathways References • Constable, A, Jonas, D, Cockburn, A, Davis, A, Edwards, G, Hepburn, P, ..., Samuels, F 2007, ‘History of safe use as applied to the safety assessment of novel foods and foods derived from genetically modified organisms’, Food and Chemical Toxicology, vol. 45, pp. 2513–2525 • Rachel S. Meyer1,2, Ashley E. DuVal3 and Helen R. Jensen (2012)Patterns and processes in crop domestication:an historical review and quantitative analysis of 203 global food crops ,New Phytologist ,196: 29–48 • • .