Transcript Scrutinizing GMO Risk Assessment Evaluating the practice

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
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Detailed look on the practice of applying the
concept of SE
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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
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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
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Compositional analyses as screening
method for unintended effects of the
genetic modification has its limitations
in particular regarding unknown antinutrients and natural toxins
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“finer screening” - DNA analysis, messengerRNA fingerprinting, protein fingerprinting,
secondary metabolite profiling and in vitro
toxicity testing
Safety Assessment of GMF
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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
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Elements to be considered in the safety
assessment process
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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
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Low-glutelin-Rice - unintended increase in
levels of prolamins (not relevant for sake-brewing but in case
of nutrition)
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would not have been detected by standard
composition analyses (total protein; AA-profiles)
„Golden Rice“ - unexpected accumulation of
xanthophylls
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would not have been apparent from standard
analyses
Substantial Equivalence
in EU-Legislation
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not explicitly detailed in EU legislation
„prominent“ role in Novel Food Regulation
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Simple procedure (Art 5)
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“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
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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).
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composition
nutritional value
metabolism
intended use
level of undesirable substances contained therein
Article 6 NF-R
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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
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90/220 (11)
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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
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97/258 (7)
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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
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SE-Data widespread – no special chapter
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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
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Maize dossiers: only descriptions of processing procedures
Rape dossiers: Data of processed products (limited scale
and set of parameters)
General Findings (2)
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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)
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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
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Significant/remarkable compositional
differences in all dossiers
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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
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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
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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)
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All but one: supplemental information
on MS-request
Findings: Compositional
Comparisons
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lack of consistency in the data provided, even
within the same plant species
Assertions of "no difference" not backed up by
hard data
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Quality of data arguable
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REP
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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
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Set of compounds not sufficient to properly assess equivalence
of nutritional value
Set of compounds not sufficient to reliably detect
secondary/unintended effects
Conclusion
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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
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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)
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Description of Trials
Design
Area AP
Climate/Soil etc
T25
Partly
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-
-
Bt11
Partly
-
-
-
MON810
-
-
-
-
MON809
-
-
-
-
Maize: Compositional Comparisons
( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11)
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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)
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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)
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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)
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Different Interpretation of „Proximates“
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3 Dossiers use expression „Proximates“
No consistency
OECD
Protein, Fat, Fibre, ADF, NDF, Ash, Carbohydrates
 NO Dossier contains data on all of these
„proximates“
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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)
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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)
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Statistics
T25
Bt11
MON810
MON809
Reference made to St.Ev. +
+
-
+
Consequent St.Ev.
+
-
-
-
Method mentioned
Partly
Partly
-
Partly
Software mentioned
-
Partly
-
-
Sheets attached
-
-
-
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Claims verifyable
Partly
-
-
-
Open questions
+
++
+++
+++
Maize: Compositional Comparisons
( HR T25, IR MON810, HR/IR MON809; HR/IR Bt-11)
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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)