Scrutinizing GMO Risk Assessment Evaluating the practice of risk assessment of GM plants and food in the EU

1. Scrutinizing GMO Risk AssessmentEvaluating the practice of risk assessmentof GM plants and food in the EU SUBSTANTIAL EQUIVALENCE and NUTRITIONAL ASPECTS Petra Lehner Workshop, Vienna 10.12.2003

2. My Part • Detailed look on the practice of applying the concept of SE • What is done by the applicants to show SE • Similarities and differences • what can be done to make compositional comparisons more reliable and consistent • look on what is done with regard to nutrition evaluation  Recommendations for further steps in order to keep the process of detailing and standardization of RA moving forward

3. Substantial Equivalence Expert Consultations convened by FAO/WHO and OECD have recommended that substantial equivalence be an important component in the safety assessment of foods derived from GMP = establishing absolute safety but to consider whether the GMF is as safe as its traditional counterpart

4. Weaknesses SE • Compositional analyses as screening method for unintended effects of the genetic modification has its limitations • in particular regarding unknown anti-nutrients and natural toxins • “finer screening” - DNA analysis, messenger-RNA fingerprinting, protein fingerprinting, secondary metabolite profiling and in vitro toxicity testing

5. Safety Assessment of GMF • directed by comparison GMF/CC • Identity, Source and Transformation Process • Recombinant DNA (stability, potential for gene transfer) • Protein Expression Product of the novel DNA (effects on function; potential toxicity; potential allergenicity) • Possible Secondary Effects from gene expression or disruption of host DNA or metabolic pathways, includingcompositionofcriticalmacro-, micro- and anti-nutrients, endogenous toxicants, allergensandphysiologically active substances • Composition • Effects of processing/cooking • Intake and dietary impact of the GMF

6. EFSA-Panel GMO • Elements to be considered in the safety assessment process • Molecular characteristics of the GMO taking into account the characteristics of the donor and recipient organisms • Potential environmental impact following a deliberate release • Compositional, nutritional, safety and agronomic characteristics • Potential toxicity and allergenicity of gene products and metabolites • Nutritional assessment of the GM food and feed

7. Nutritional Evaluation • Low-glutelin-Rice - unintended increase in levels of prolamins(not relevant for sake-brewing but in case of nutrition) • would not have been detected by standard composition analyses (total protein; AA-profiles) • „Golden Rice“ - unexpected accumulation of xanthophylls • would not have been apparent from standard analyses

8. not explicitly detailed in EU legislation „prominent“ role in Novel Food Regulation Simple procedure (Art 5) “Substantial Equivalence” on the basis of the scientific evidence available and generally recognized or on the basis of an opinion delivered by one of the competent bodies Substantial Equivalence in EU-Legislation

9. Article 5 NF-R • In the case of the foods or food ingredients referred to in Article 3 (4), the applicant shall notify the Commission of the placing on the market when he does so. Such notification shall be accompanied by the relevant details provided for in Article 3 (4). • composition • nutritional value • metabolism • intended use • level of undesirable substances contained therein

10. Article 6 NF-R • The request referred to in Article 4 (1) (=application for placing on the market) shall contain the necessary information, including a copy of the studies which have been carried out and any other material which is available to demonstrate that the food or food ingredient complies with the criteria laid down in Article 3 .1

11. 90/220 (11) Rape Topas 19/2 (food-use included) Maize Bt-11 (food-use included) – “twin” Maize RR GA21 – “twin” Cotton Bt-531 Cotton RR 1445 RR-Fodder beet A5/15 Potato EH92-527-1 Carnation 66 Carnation 959A 97/258 (7) Rape RF1MS1, RF1MS2 Rape Topas 19/2 Rape GT73 Maize Bt-11 Maize T25 Maize MON 809 Maize MON 810 Evaluated Dossiers NO ADDITIONAL DATA NF-Application Rape Topas 19/2 and Maize Bt-11

12. General Findings • SE-Data widespread – no special chapter • composition data of raw products and/or processed products and/or information on processing (and exposition and/or consumption) are scattered throughout dossiers • Dossiers are not “stand alone” • Composition analyses: GLP not evident • Analyses of kernels – extended to processed products • Maize dossiers: only descriptions of processing procedures • Rape dossiers: Data of processed products (limited scale and set of parameters)

13. General Findings (2) • Barely Data on Consumption • Field trials/Sampling not described in detail • Only one dossier: isogenic counterpart • No herbicide-application in case of HR-GMP • No information on sample storage • Methods and Practice of Analysing rarely specified (Reps, Method-Errors, Detection-Limits etc) • Discontenting presentation of data

14. General Findings (3) • Solid statistical evaluation questionable • No continuous statistic evaluation • Missing information on methods/software/CI --> Cannot be concluded, that in each case the statistical evaluation is actually state of the art • Significant/remarkable compositional differences in all dossiers • Differences dismissed without adequate explanation or by arbitrarily citing literature ranges or „normal“ ranges • No rerun of analyses taking into account a broader spectrum of compounds • To get a better overview on compositional equivalence and • To better address the hazard of secondary/unintended effects

15. General Findings (4) • All dossiers evaluated by ACNFP/UK • Mandatory monitoring for all • Applicants are bound to monitor composition of seeds/kernels and/or oil over time • No concrete requirements • No additional information (all products were approved in UK at time of application) • All but one: supplemental information on MS-request

16. Findings: Compositional Comparisons • lack of consistency in the data provided, even within the same plant species • Assertions of "no difference" not backed up by hard data • Quality of data arguable • Design of field trials / Replications / Conventional Counterpart • GLP / Double-testing / Reporting • Lacking plausibility that Compositional Data have been analysed in a statistically sound way • Comprehensiveness • Set of compounds not sufficient to properly assess equivalence of nutritional value • Set of compounds not sufficient to reliably detect secondary/unintended effects REP

17. Conclusion • inconsistency and sometimes lack of useful data demonstrate the need for guidelines in order to harmonise and co-ordinate the basis requirement of data for comparison

18. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Base material: kernels • Field trials

19. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Description of Trials

20. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Sampling

21. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Analysing

22. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Macro-Compounds – „Proximates“

23. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Different Interpretation of „Proximates“ • 3 Dossiers use expression „Proximates“ • No consistency • OECD • Protein, Fat, Fibre, ADF, NDF, Ash, Carbohydrates  NO Dossier contains data on all of these „proximates“ NEED FOR HARMONISATION

24. Prot Fat CH Fibre ADF NDF Ash OECD + + + + + + + EuropaBio + + - - - - + T25 + + + + - - + MON 809 + + + - - - + MON 810 1994 + + + - - - + MON 810 1995 + + + - + + + Bt11 „Grain properties“ - P, F, Starch, Fibre „Proximates“

25. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Micro-Compounds

26. OECD EuropaBio T25 Bt11 MON 810 MON 809 AS (18)a % n.R. + + - + + FS (5)b % n.R. + + - + + Amino Acids and Fatty Acids a) Ala, Arg, Asp, Cys, Iso, His, Glu, Gly, Leu, Lys, Met, Phe, Pro, Ser, Thr, Tyr, Try, Val; b) Palmitic-, Stearic-, Oleic-, Linoleic-, Linolenicacid

27. Vitamin mg/kg OECD EuroB T25 Bt11 M810 M809 Retinolequivalent + - - - - - Vit B1 + + - + - - Vit B2 + + - + - - Vit B6 + - - - - - Vit E + + - - - - Folate total + + - + - - Niacin (nicotinic acid) + - - + - - Vitamins

28. Mineral mg/100g OECD EuroB T25 Bt11 M810 M809 Ca + + - - - - K + + - - - - Mg + + - +. - - Na + + - - - - P + + - - - - Cu + - - + - - Fe + - - - - - Se + - - - - - Zn + - - + - - Minerals

29. Compound OECD EuroB T25 Bt11 M810 M809 Phytic Acid % TG + + - - - - Raffinose % n.k.. + - - - - Furfural ppm + - - - - Ferulic Acid % n.k.. + - - - - - p-Coumaric Acid n.k. + - - - - - Other Compounds

30. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Statistics

31. Maize: Compositional Comparisons( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) • Processed Products – Composition Analyses !!! In OECD-ConsDoc the Composition of different processed maize-products is mentioned (oil, grit, flakes, meal, starch)