Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Scrutinizing GMO Risk Assessment Evaluating the practice of risk assessment of GM plants and food in the EU SUBSTANTIAL EQUIVALENCE and NUTRITIONAL ASPECTS Petra Lehner Workshop, Vienna 10.12.2003 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 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 Weaknesses SE Compositional analyses as screening method for unintended effects of the genetic modification has its limitations in particular regarding unknown antinutrients and natural toxins “finer screening” - DNA analysis, messengerRNA fingerprinting, protein fingerprinting, secondary metabolite profiling and in vitro toxicity testing 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, including composition of critical macro-, micro- and anti-nutrients, endogenous toxicants, allergens and physiologically active substances Composition Effects of processing/cooking Intake and dietary impact of the GMF 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 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 Substantial Equivalence in EU-Legislation 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 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 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 Evaluated Dossiers 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 NO ADDITIONAL DATA NF-Application Rape Topas 19/2 and Maize Bt-11 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) 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 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 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 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 REP 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 Conclusion inconsistency and sometimes lack of useful data demonstrate the need for guidelines in order to harmonise and coordinate the basis requirement of data for comparison Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Base material: kernels Field trials Seasons Sites Counterpart T25 1 2 iso+sim Bt11 1 + GH 12 isogen MON 810 2 6/5 similar MON 809 1 6 similar Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Description of Trials Design Area AP Climate/Soil etc T25 Partly - - - Bt11 Partly - - - MON810 - - - - MON809 - - - - Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Sampling Taking Storing Preparation T25 + - Partly Bt11 Partly - Partly MON810 Partly - Partly MON809 Partly - Partly Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Analysing Method Practice Journal T25 + Partly + Bt11 Partly Partly - MON810 References - - MON809 References - - Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Macro-Compounds – „Proximates“ T25 Bt11 MON810 MON809 Protein % DW % n.R. % DW % DW Nitrogen - % DW - - Fat % DW % n.R. % DW % DW Carbohyd. % DW - % DW % DW Starch - % DW - - Ash % DW % DW % DW % DW Fibre % DW % n.R. - - ADF - - % DW - NDF - - % DW - Moisture % % % % 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 „Proximates“ 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 Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Micro-Compounds T25 Bt11 MON810 MON809 Fatty Acids % Fat % n.R. % Fat - Amino acids % MM g/kg DS % Protein - Cellulose - % DW - - Xanthophylls - mg/kg DW - - Vit B1 - mg/lb - - Vit B2 - mg/lb - - Niacin - mg/lb - - Folic Acid - mg/lb - - Cu, Mg, Mn, Zn - % n.R. - - Amino Acids and Fatty Acids OECD EuropaBio T25 Bt11 MON 810 MON 809 AS (18)a % n.R. + + - + + FS (5)b % n.R. + + - + + 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 Vitamins Vitamin mg/kg OECD EuroB T25 Bt11 M810 M809 Retinolequivalent + - - - - - Vit B1 + + - + - - Vit B2 + + - + - - Vit B6 + - - - - - Vit E + + - - - - Folate total + + - + - - Niacin (nicotinic acid) + - - + - - Minerals Mineral mg/100g OECD EuroB T25 Bt11 M810 M809 Ca + + - - - - K + + - - - - Mg + + - +. - - Na + + - - - - P + + - - - - Cu + - - + - - Fe + - - - - - Se + - - - - - Zn + - - + - - Other Compounds Compound OECD EuroB T25 Bt11 M810 M809 Phytic Acid % TG + + - - - - Raffinose % n.k.. + - - - - Furfural ppm + - - - - Ferulic Acid % n.k.. + - - - - - p-Coumaric Acid n.k. + - - - - - Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Statistics T25 Bt11 MON810 MON809 Reference made to St.Ev. + + - + Consequent St.Ev. + - - - Method mentioned Partly Partly - Partly Software mentioned - Partly - - Sheets attached - - - - Claims verifyable Partly - - - Open questions + ++ +++ +++ Maize: Compositional Comparisons ( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11) Processed Products – Composition Analyses Basic intermediates Final products T25 - Bt11 - MON810 MON809 - - - - - !!! In OECD-ConsDoc the Composition of different processed maize-products is mentioned (oil, grit, flakes, meal, starch)