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  ANNEX H 
 
REPLIES BY THE SCIENTIFIC EXPERTS ADVISING THE PANEL 
TO QUESTIONS POSED BY THE PANEL 
 
 
GENERAL COMMENTS OF THE EXPERTS  
 
Dr. Snow  
A. WHICH ENVIRONMENTAL CONCERNS ABOUT GM  CROPS ARE REALLY "SCIENCE -BASED "? 
1. A great deal has been written on this topic, and I will not try to summarize all of it here.  Most 
hypothetical concerns pertaining to environmental effects of GM crops are included in the following 
list from the Ecological Society of America (Snow et al. 2005).  Risk assessments are needed to 
minimize the likelihood of: 
• creating new or more vigorous pests and pathogens; 
• exacerbating the effects of existing pests thr ough hybridization with related transgenic 
organisms; 
• harming non-target species, such as soil organisms, non-pest insects, birds, and other flora 
and fauna; 
• disrupting biotic communities, including agroecosystems;  
• causing irreparable loss or changes in species di versity or genetic diversity within species. 
2. Clearly, many GM crops are unlikely to cause an y of these potential problems.  Furthermore, 
it is not logical to group all GM crops into a si ngle category and conclude that they are either 
inherently safe or inherently dangerous (see Question 103 below).  It is important to evaluate new GM crops on a case-by-case basis in each country where the crop will be grown, and to do so using 
appropriate baseline comparisons.  In the United States, for example, each new GM variety is 
compared to its non-GM predecessor in the context of conventional agricultural practices, and in the 
context of the nation's overall stra tegy for how its agricultural, environmental, and trade policies are 
implemented.   
3. Some of the environmental concerns that EC Me mber States have raised in the documents are 
similar to concerns that routinely are addressed  by regulatory agencies of the Complainants.  
However, there are also major differences in re gulatory goals and policies.  For example, the 
conservation of farmland biodiversity is a much bigger issue in Europe than in the USA or Canada (I 
am not familiar with the situation in Argentina).  In some European countries, much of the non-urban 
landscape consists of farmland, which is the prim ary habitat for native insects, birds, and other 
animals.  Also, EC Member States' strategies to manage and/or reduce herbicide applications differ 
from policies of the Complainants.  In addition, the EC requires post-release monitoring to check for 
unanticipated environmental problems, reflecting a more cautious approach to risk assessment.  The 
overall philosophy of EC Directive 2001/18 differs radi cally from regulations of the Complainants by 
emphasizing the possibility of cumulative and long-te rm hazards that could be caused by GM crops, 
and the need for precautionary decision-making to avoid irreversible harm to the environment.  
Ultimately, with regard to the Panel's questions  about scientific issues, it may be useful to WT/DS291/R/Add.6 
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  acknowledge these major differences between the dis puting parties in their environmental and public 
health goals and their strategies for reaching these goals. 
4. Some of the delays in EC regulatory decisions c ould be related to the time needed to develop 
new legislation that pertains to labeling (e.g., Re gulation 1830/2003).  Also, there were many requests 
for new information to be added to notifications wh en EC Directive 90/220, which had been in effect 
since 1990, was replaced by Directive 2001/18 in March 2001.   The new Directive includes 
requirements for labeling and traceability, as well as consideration of socioeconomic and ethical issues.    
5. Another question that has been raised in Europe is how to ensure that GM crops can "coexist" 
with non-GM crops, including both c onventional and organic crops, such that current and future 
labeling standards can be met.  I will not attempt to  address this socioeconomic and legal issue, other 
than to note that scientific information about ge ne flow is often releva nt to questions about 
coexistence.  In some cases, further research may be needed to fill information gaps.  
6. As a scientific advisor to the Panel, I am restricting my comments to over-arching questions 
about whether various Member States had valid reasons  to conclude that additional scientific research 
was needed to complete their environm ental risk assessments in 1998-2003.   
7. Below, I list questions about possible envi ronmental problems that could result from 
cultivating the specific GM crops that are cited in this dispute.  These concerns apply mainly to 
agricultural landscapes rather than other managed or natural habitats for flora and fauna.  For each 
new GM variety, one can ask whether its widesp read cultivation is likely to cause any of the 
following outcomes to a greater degree than corresponding non-GM varieties: 
a. create or exacerbate weed problems 
b. cause direct or indirect harm to non-target species, including: 
i. beneficial insects and soil organisms that affect crop yields 
ii. native flora and fauna, including culturally important species 
- e.g., native butterflies, skylarks, wild relatives of 
crop plants 
c. lead to the use of more herbicides or insecticides, including more toxic ones, 
potentially harming flora, fauna, and human health. 
Gene flow and the concept of "genetic pollution"  
 
8. I will focus most of my comments on the environmental effects of gene flow from GM crops.  
In this context, the dispersal of transgenes by pollen or seeds is not a problem, in and of itself, unless 
this process has unwanted biological consequences.  From this standpoint, the presence of transgenes 
in non-GM crops, wild relatives, or weeds can be se en as being part of a normal process that occurs 
with all crop genes.  It is well known that crop genes can disperse widely by means of pollen and 
seeds.  Only certain types of new genes, such as those that confer herbicide resistance or cause harm 
to non-target species, might lead to unwanted biological consequences.      WT/DS291/R/Add.6 
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  9. The mere fact that GM crops are regulated may cause some people to conclude that all 
transgenes are risky.  I do not agree with this opini on, as I discuss in my answer to Question 103.  The 
process of artificially inserting genes into a plant's DNA can have unintended consequences, such as 
abnormal growth or development, but it is unlik ely that 1) these effects will be ecologically 
significant in commercially-produced transgenic crops, or 2) they would be more risky than the types 
of side-effects that arise routinely during conventio nal breeding.  In any case, many scientists agree 
that genetically modified plants should be judge d on the basis of their phenotype – their actual 
characteristics – rather than the pr ocess that is used to develop them (e.g., Tiedje et al. 1989, NRC 
2000, Snow 2003).   
10. Moreover, there is no reason to expect that tr ansgenes could be harmful simply because they 
are released in a particular crop's center of divers ity (i.e., where many of the crop's wild ancestors or 
original cultivars occur; e.g., Gepts and Papa 2003, Bellon and Berthaud 2004).  This topic has 
received a good deal of publicity, but there is no reason to expect that the effects of gene flow from modern cultivars on the genetic diversity of  wild relatives differ between transgenic vs. nontransgenic 
crops.  As stated above, gene flow do es not represent an environmental concern per se , unless it 
results in unwanted biologi cal consequences.  If there are  unwanted consequences, the extent to 
which the transgenes disperse via pollen and seeds may be analogous to the "exposure" term in the 
simple risk assessment equation "risk = exposure x harm", in which these terms are expressed as 
probabilities.   
11. The documents in this dispute indicate that some  Member States consider transgenes to be a 
type of genetic pollution, even th ough these genes are unlikely to have any negative effects on plants, 
animals, human health, or the environment.  For example, Greece stated concerns about herbicide 
resistance transgenes from imported oilseed rape that is not intende d for cultivation (see Question 66).  
Here the perceived risk appears to be that  the transgenes would be harmful to native Brassica  species.  
I do not agree that this would be a problem beca use 1) the imported seeds would not be cultivated 
(though some mix-ups with seed sources could occur), and 2) the transgene in question – a gene that confers resistance to the herbicide glufosin ate – is unlikely to be harmful to native Brassica species in 
Greece, should they eventually hybridize with crop pl ants.  Even if transgen ic seeds of oilseed rape 
were to leak into the local farming system, perhaps establishing volunteer populations of oilseed rape, 
it is difficult to imagine how a transgene that confer s resistance to glufosinate could be harmful to 
wild relatives of the crop. 
B. SCIENTIFIC UNCERTAINTY DURING 1998-2003 
12. Biotechnology companies have been evaluati ng characteristics of GM crops for over two 
decades.  As of 1998, however, the USA, Canada, and Argentina had only two years of experience 
with commercial-scale cultivation of transgenic Bt and herbicide-tolera nt crops.  Independent 
researchers who study environmental effects of GM crops had even less experience, partly because 
funding for this research was meager given the scope of key questions (e.g., Tiedje et al. 1989, Snow and Moran-Palma 1997, Snow 2002, Snow et al. 2005).  Also, it has often been impossible for 
independent researchers to gain access to GM plants for field studies that precede deregulation (Dalton 2002).  Rigorous ecological research typica lly requires several years and multiple teams of 
researchers to answer seemingly simple questions such as:  
• Will pollen from Bt maize (corn) be harmful to native butterflies? 
• Will volunteer plants from herbicide-tolera nt oilseed rape become problematic 
weeds? 
• How will farmland wildlife be affected by the cultivation of new GM crops as compared to current crops? WT/DS291/R/Add.6 
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13. Therefore, from 1998-2003, many ecological qu estions about current and planned GM crops 
were just beginning to be addressed. 
14. When additional  scientific knowledge is needed to evaluate new GM crops, each nation's 
regulators and scientific advisory committees are placed in the difficult position of choosing between 
expediency and greater certainty.  It is not alwa ys clear where the distinction lies between what 
regulators "need to know" vs. what is merely "nice to know".  Regulators often have to rely on 
intuition or small-scale, unpublished studies, some of  which lack adequate statistical tests (e.g. 
Marvier 2002).  The routine, agronomic field trials that are conducted by biotech companies prior to deregulation are rarely intended to answer ecological -scale questions, nor would they be sufficient.  
Moreover, regulators and scientific advisory committ ees may not have the insight to correctly identify 
all of the potential risks that should be considered for each GM crop that is proposed for deregulation.  
In recent years, the hotly contested political, socio- economic, and ethical questions that pertain to GM 
crops have made it even more difficult to find the appropriate balance between expediency and 
certainty.   
15. Scientific research can play an important role  in how GM crops are evaluated by confirming 
or refuting widely held assumptions.  Findings that are published in peer-reviewed scientific journals 
help define and answer key scientific questions that  relate to risk assessments.  Below, I include a 
sample of recent publications (1994-2003) that are relevant to this dispute because they illustrate 
recent discoveries.  Several of these papers challe nged widely held assumptions about pollen, gene 
flow, or herbicide-tolerant crops.  The context for these papers should become clear in light of my answers to the questions from the Panel.  Papers that  appeared in four high-profile journals – Nature, 
Science, Philosophical Transactions of the Royal Society of London, and Proceedings of the US National Academy of Sciences – may have had the biggest impact on European decision-makers' 
perceptions about environmental effects of GM crops.   
Examples of recent scientific findings about pollen, gene flow, and herbicide-tolerant crops : 
 
(Listed in chronological order; see References for complete citations.) 
 
1. Crop genes can spread from oilseed rape to populations of weedy Brassica rapa, contrary to 
previous expectations. 
Jeorgensen and Andersen 1994.  American Journal of Botany . 
2. Transgenes that confer herb icide resistance can spread from oilseed rape to populations of 
weedy Brassica rapa (not surprising based on the paper listed above, although this article 
received a great deal of attention). 
Mikkelsen et al. 1996.  Nature.  
3. Oilseed rape transgenes that confer herbicid e resistance and spread to wild relatives do not 
harm weedy Brassica rapa, even in the absence of herbicide use. 
 Snow et al. 1998. Molecular Ecology. 
4. Transgenic pollen from Bt maize is harmfu l to monarch butterfly larvae under laboratory 
conditions. 
Losey et al. 1999.  Nature.   
In 2001, several follow-up papers in the Proceedings of the US National Academy of 
Sciences  (e.g., Sears et al. 2001) concluded that th is is not a problem under field conditions;  WT/DS291/R/Add.6 
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  in contrast, Jesse and Obrycki (2000; Oecologia ) did find evidence for harmful effects on 
monarch butterfly larvae under field conditions. 
5. Pollen flow among fields of herbicide-tolerant oilseed rape  in Canada can lead to the 
emergence of weedy volunteer plants (from unharvested seeds) that are resistant to three types 
of herbicides. 
 Hall et al. 2000.  Weed Science . 
6. A modeling study showed that more effective control of weeds, for example in fields of 
herbicide-tolerant crops, could reduce the food su pply of declining populations of skylarks in 
the UK. 
Watkinson et al. 2000.  Science .  
7.  Feral populations of oilseed rape can persist outside of cultivated fields for more than eight 
years, contrary to previous expectations.  This  study showed that pers istent feral populations 
can originate from earlier varieties of the crop that are no longer planted. 
Pessel et al. 2001.  Theoretical and Applied Genetics .   
8. Transgenes were discovered in locally pro duced landraces of maize in remote areas of 
Mexico, despite a national moratorium on planting transgenic maize. 
Quist and Chapela. 2001.  Nature.  
(This finding was confirmed by further studies, while other conclusions in this controversial 
paper have largely been discounted.) 
9. Unharvested and spilled oilseed rape seeds can acquire secondary seed dormancy and may 
persist for five years or longer in no-till as well as tilled systems, contrary to previous expectations.  Previous studies suggested th at seeds from the crop would be unlikely to 
acquire secondary seed dormancy under no-till conditions. 
Simard et al. 2002.  Weed Technology .  
10. Pollen from oilseed rape fields can travel at  least three kilometers away from source fields, 
thereby allowing cross-pollination to occur ove r much greater distances than previously 
expected. 
 Reiger et al. 2002.  Science . 
11. Hybridization between transgenic oilseed rape and weedy Brassica rapa is inevitable in the 
UK, further demonstrating difficulties of confinin g gene flow if this is deemed necessary. 
Wilkinson et al. 2003.  Science . 
12. Widespread adoption of glufos inate-tolerant oilseed rape and sugar beet might be harmful to 
the biodiversity of agroecosystems in the UK, as compared to effects of  currently used non-
tolerant varieties. 
Results of government-sponsored Farm Scale Evaluations. Philosophical Transactions of 
the Royal Society of London  (several papers, including Firbank 2003, Squire et al. 2003). 
13. In Canada, non-GM oilseed rape seeds that were sold to farmers were often contaminated 
with small amounts of seeds that had transgenic  resistance to two herbicides, glyphosate and 
glufosinate.  This exacerbated the emergi ng problem of volunteer canola plants with 
glyphosate resistance, a trend that might jeopa rdize the use of low-tillage weed control. 
Freisen et al. 2003. Agronomy Journal . WT/DS291/R/Add.6 
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  16. These publications illustrate that even within the specialized area of gene flow and herbicide-
tolerant crops, new findings and new unanswered questions repeatedly appeared in prominent 
scientific journals between 1998 and 2003.  Th is undoubtedly contributed to science-based 
considerations of various Competent Authorities in  Europe.  Unfortunately, results from these papers 
have often been distorted by the media and others, leading to a great deal of flawed information about 
the actual content and the inherent strengths and li mitations of these studies.  In this climate of 
controversy and distrust, some of the publicity abou t risks of biotech crops has led to exaggerated 
concerns about environmental risks.  At the same time, the biotech industry so metimes is perceived as 
being unaware of or unconcerned about valid environmental risks that are taken seriously by 
professional scientists and others (e.g., Gray 2004). 
17. As new publications appeared in the scientific literature during 1998- 2003, decision-makers 
saw that transgenes are expected to spread very widely by means of pollen and seeds, and that 
therefore these genes could show up in certified seed s sold to farmers, farmer-saved seeds, volunteer 
plants, and weedy or wild relatives of the crop.  Ev en in maize, which has no wild relatives or feral 
populations in the USA, and which must be purchased anew each year to achieve high yields, experience with Starlink corn showed how difficult it is to prevent unwanted genes from re-appearing 
year after year.  After Starlink was taken off the market, its unauthorized Bt gene ( cry9C) continued to 
be present in trace amounts in the US grain supply three years later (USDA 2003, Marvier and Van Acker 2005).  Evidence that transgenes could be pr esent in freely reproducing plants over very large 
areas shows that "calling them back" will not be pr actical for crops like oilseed rape.  Therefore, 
scientific advisors of some Member States cautioned against approving certain notifications until the environmental and economic effects of commerc ialization were understood more thoroughly. 
18. While new questions were bei ng raised about specific GM crops during 1998-2003, many 
reports stated that the GM crops grown in North America were neutral or beneficial from an 
environmental standpoint.   Regulatory agencies a nd biotech companies in the USA assume that 
transgenic crops that are approved for commercia l production are no more ri sky than nontransgenic 
crops.  The US National Research Council, which is independent of the government, published two 
critiques of regulatory approvals of the first GM crop varieties in the US (NRC 2000, 2002).  These 
critiques included suggestions for how to improve the regulatory process to make it more rigorous, but they did not question the safety of products that  had been approved for marketing.  To date, no 
clear environmental problems have been identified from the cultivation of GM soybean, cotton, or 
maize in the USA.  In Canada, one problem that has arisen from growing herbicide-resistant oilseed rape (canola) is the emergence herbicide-resistant volunteers that are more difficult to manage than 
normal volunteers (e.g., Hall et al. 2000, Friesen et al. 2003).   
19. Here, it is important to recall that the pe riod during which GM crops have been grown 
commercially is relatively short, having begun in 1996-1997.  This is not much time for noticing 
major environmental effects of GM varieties.  In the USA, for instance, little attention has been paid to documenting positive or negative effects on biodiversity empirically, and many types of effects are not expected to be obvious to casual observe rs (e.g., NRC 2002, Snow et al. 2005).    
C. SPECIAL CONCERNS ABOUT THE LONG -TERM EFFICACY OF BT CROPS AND THE HERBICIDE 
GLYPHOSATE  
20. The most widely used transgenes in commercial GM crops are various Bt transgenes and 
those that confer resistance to glyphosate.  These transgenes deserve special consideration because of 
the environmental and health benefits they can sometimes provide, relative to current pesticide 
practices, and because their effectivenes s could be lost if the target p ests evolve resistance to the Bt 
pesticide or the herbicide glyphosate.  This is di fferent from other types of possible risks, such as  WT/DS291/R/Add.6 
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                                                       greater allergenicity, because it deals with the loss of a benefit rather than the creation of a risk.  First, 
I briefly summarize the benefits of Bt crops. 
21. Plant-produced Bt proteins can be more effec tive at controlling insect pests than chemical 
sprays because they kill insects th at feed inside the plant, wh ere sprays cannot reach, and these 
proteins are produced continuously throughout the season.  In crops like cotton, which requires heavy insecticide applications, the use of Bt cotton substitutes for many of these broader-spectrum 
insecticides.  This can be beneficial to farm work ers' health, populations of non-target and beneficial 
insects, and the environment.  Similar benefits can be seen with Bt maize, but only in regions where 
insecticide use is deemed necessary to begin with.  The high specificity, low toxicity, and agronomic benefits of Bt proteins make them extremely valu able, especially in comparison to standard practices 
in chemical-intensive conventional agriculture.   
22. One of the risks associated with Bt crops is that target insects could become resistant to these 
Bt proteins, and therefore a valuable method of insect control would be lost.  Because of these 
concerns, many countries in which Bt crops ar e grown have developed formal or informal 
management strategies to delay the evolution of target insect pests that are resistant to Bt proteins. 
23. A somewhat similar situation exists with  the herbicide glyphosate (sold as Round-UpTM).  
This herbicide is extremely effective at killing most  species of weeds and, compared to many other 
herbicides, it breaks down relatively quickly after use.  Thus, it is much easier and safer to use than 
herbicides such as 2,4-D, although some crops can thrive with little or no  herbicide treatment 
(baseline levels of herbicide use vary among crops, countries, and farmers).  Glyphosate is relatively 
inexpensive and it is widely available in many c ountries.  In North America, large-scale conventional 
farmers often use glyphosate for general weed c ontrol and for no-till and low-till cultivation, which 
has several environmental benefits (e.g., reducing erosion and siltation).      
24. Despite heavy use of this herbicide over the past twenty years, few weed species have 
evolved resistance to glyphosate, in contrast to the large numbers of weed species that are resistant to other herbicides like imidazolinone (WSSA 2005).  The problem of allowing more and more types of 
weeds to become resistant to co mmonly used herbicides is widely recognized by weed scientists, 
biotech companies, and farmers, but few countries ha ve implemented effective strategies to delay the 
evolution of resistance. 
25. Like Bt, glyphosate has been very popular with farmers and its use has increased substantially 
with the adoption of glyphosate-tolera nt crops.  As with Bt, one of the risks associated with the spread 
of resistance genes in pests (in this case, weeds an d volunteer plants) is the loss of a benefit that is 
associated with this particular herbicide.  To summarize, Bt crops and glyphosate offer potential benefits to both farmers and the environment, and scientists are skeptical about whether they could be 
replaced in kind if target pests – be they insects or weeds – evolve resistance.  Therefore, many 
scientists, farmers, and decision-makers are work ing on methods to prolong the efficacy of Bt, 
glyphosate, and glyphosate-tolerant GM crops.
1 
 
1 References Dr. Snow: 
 
Note: Papers cited in this report are underlined.   
 
This reference list includes a large proportion of peer-reviewed papers about gene flow from oilseed 
rape, which is the focus of my answers.  Numerous publications are relevant to these questions, including 
citations listed in a recent review by Devos et al. (2005).  
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  Dr. Squire  
Notes on ecological and environmental standards  
26. These notes are intended to summarise my views on some general issues pertaining to the 
questions set by the panel. The notes touch on –the general weakness of current  criteria and standards, 
particular in relation to ecological  topics, by which products of the type under review might be 
judged, the importance of context and scale when as sessing new global products for specific markets, 
some recent and current  research in geneflow and ecological impacts. 
Criteria and standards  
Information required to prove that a biotech product is safe 
27. No product can be assessed as being absolutely safe. There seems to be general agreement on 
that. However, there is no general agreement on what should be considered as acceptably safe. As 
information is first gathered on a product, the likelihood that the product is safe or not may increase quite steeply, but gradually each further piece of information comes to contributes less and less to the 
likelihood that the product is saf e. (The knowledge/safety curve assumes the form of 'diminishing 
returns'). Among the present arguments, however, there seems no agreement as to when there is 
                                                                                                                                                                     
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  enough information to satisfy all reasonable parties that  a product is safe. This is largely because there 
is no benchmark or set of standards by which ecological safety can be judged. 
28. There is an important set of exceptions to the 'diminishing returns' shape of a 
knowledge/safety curve. If the body of knowledge rev eals a new property of the biotech product, or if 
the external 'environment' – the context – change s, then the knowledge/safety curve could well 
steepen again because much additional knowledge is th en required to ascertain that the product is safe 
in relation to the new property or context. In some instances, new properties might emerge only after a 
product is grown over a period of tim e or over a wide area of land.  Several of the arguments and 
uncertainties in the dispute over geneflow and cont amination are of this type: current knowledge 
seems insufficient to model and predict the extent of a potential problem.  
International Standards and Guidelines  
29. The standards and guidelines referred to in the panel's questions are (to this reviewer) 
important steps towards an agreed set of standards.  They differ in their stringency and required detail. 
Recommendations are relatively well defined and stringent in the WTO Sanitory and Phytosanitory Measures , in ISPM 11, and in the Guideline for the Conduct of Food Safety Assessment of foods 
derived from recombinant-DNA plants .  The latter in particular requires great detail in characterising 
and describing the genetic material, plant metabolites and other constituents. Many of the 'requests for 
further information' by the EC or its member states are consistent with (i.e. not beyond) the level of 
detail indicated in that publication. 
30. Less detailed and prescriptive are the 'Proposed  draft annex on the assessment of possible 
allergenicity.....'  and the Annex III of the Cartag ena protocol on biosafety to the Convention on 
Biological Diversity'. Both offer less well defined guidelines, largely because the issues (allergenicity, impact on ecosystems) are complex and, as indicated at paragraphs 2 and 7, there are no or few obvious quantitative criteria on which to base assessm ents. This weakness of criteria makes risk 
assessment very difficult in relation to these topics.  
31. As many others have said, non-biotech crop plants  are not subjected to anything like the same 
degree of testing as biotech plants. If they had been, the ecological standards might now be in place. 
Criteria and comparators for ecological effects  
32. Many of the arguments around the ecological benef its or harm of biotech crops are carried on 
without reference to objective criteria.  Annex III of the Cartagena Protocol on Biosafety to the 
Convention of Biological Diversity  indicates only the general type of information that might be 
considered. Even when discussing specific products in relation to specific ecosystems, neither the 
biotech companies nor the responding EC bodies refer to objective criteria when stating that a product 
is safe or not. For instance, an assessing body might require more information on long-term ecological safety without stating what type of information is necessary to ascertain safety.  
33. The problems referred to in paragraph 7 arise because we lack a set of properties –physical, 
chemical, biological, social and economic – which de fine that a production system is resilient and 
'healthy'. As a stop-gap, ecological studies have compared GM products with non-GM isogenic lines 
when making initial comparisons on a small scale, and then with another agronomic practice when 
making comparisons on a field scale. Even when a comparator is used (e.g. current practice), it is not yet clear that the comparator is an appropriate st andard, one that will sustai n crop production. Neither 
side in the argument over any product has indicated, even in general terms, what a suitable set of ecological standards might be.   WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  Scale and context in assessing biodi versity and ecological impact  
34. The arguments in paragraphs 7 and 8 are complicated further because ecological criteria will 
be influenced by the context – the combination of weather, soil, landscape, the agronomy and 
economics – of which the flora and fauna are an essential part. The compan ies seem to have been 
unaware of, or not appreciated, the context in wh ich biodiversity exists when presenting many of the 
cases in support of their products. Biodiversity is important primarily because it keeps an ecosystem 
intact and functioning and makes it resilient to ex ternal perturbations. The diversity-function relation 
– i.e. that diversity in microorganisms, plants a nd animals is required to maintain essential functions 
such as decomposition, nutrient transformations, soil fo rmation, detoxification, regulating pests, etc. – 
has been largely ignored in arguments over the safety of biotech crops (and non-biotech crops).   
35. It is necessary therefore that the biodiversity in the cropped field is taken into account as 
much as the biodiversity of the semi-natural  habitats surrounding agriculture. Moreover  
• what is considered the valuable biodiversity in one part of the world might be very 
different from what is considered valuable in another part, and  
 
• a product that is considered to have negligib le impact on total biodiversity in one part 
of the world might have a large effect in another (and vice versa).  
 
36. There are some large differences between Eur ope and North America in these respects. In 
many parts of Europe, valuable biodiversity is cons idered not just that of natural and semi-natural 
areas (mountains, extensive forests), but must include the flora and fauna within arable fields, both for 
the reasons in paragraph 9 above (i.e. the divers ity-function relation) and because biodiversity in the 
form of farmland plants, insects and birds is  perceived by people as being valuable.  
37. Emergent properties at the landscape scale . Moreover, it is scientifically unreasonable to 
assume that an effect (positive or negative), or the absence of effect, of a biotech product when measured at the scale of the single plant or small fi eld plot will be the same when measured at the 
scale of the field, farm or landscape. Up-scaling of biological effect to the landscape was a major 
topic of research in the 1990s and still is. Questions include - 
• Will cross-pollination frequencies at a fiel d or feral population rise substantially as 
the proportional area of a donor type increases in the landscape? 
 
• Will volunteer and feral populations become more competitive and longer persisting as they evolve through selection and the incorporation of new traits? 
 
• To what extent will variation in local ph ysical conditions and occasional human error 
seriously reduce the efficacy of mitigation protocols? 
 
38. One of the main difficulties in predicting the effect of any type of innovation is still the 
uncertainty over up-scaling. What will happen as more and more of the land area is affected by the 
innovation? Again, progress is limited by the absence of hard criteria that define resilient or sustainable states at the scales in question.  
New research since 1998 on relevant ecological topics  
39. In part to address issues in paragraphs 8 to 12, a large body of research has been 
commissioned on ecological impacts and geneflow in  Europe. Much of the previous research on GM WT/DS291/R/Add.6 
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  plants in the early and mid-1990s compared genetic  lines with and without a GM trait, either in 
containment, or in small areas of field. Howeve r, it was increasingly accepted during the 1990s that 
this was insufficient to provide knowledge of the spread, persistence and ecological effects of biotech 
crops at scales of the field and landscape. An im portant watershed was the symposium held in 1999 – 
Geneflow in agriculture:  relevance for transgenic crops  – which brought together researchers from 
Europe and North America to compare latest studi es on geneflow and persis tence of GM and non-GM 
crops in the environment. This symposium drew atte ntion to the fact that geneflow at the landscape-
scale had spatial and temporal features that were not evident at smaller scales of study. 
Geneflow in Agriculture: relevance for tr ansgenic crops. (1999)  Proceedings of a 
Symposium held at the University of Keele, 12-14 April 1999. Chaired by PJW 
Lutman. British Crop Protecti on Council, Farnham, UK. 
40. Both the EC and several EC countries have commissioned multi-partner studies on geneflow 
and GM impacts.  Results are reported for some stud ies; others are in progress or partly completed. 
They include the following projects. 
• SIGMEA – Sustainable Introduction of GM crops into European Agriculture (http://sigmea.dyndns.org/) a EC-funded pr oject which began in 2004 and has the 
main aims of (a) collating European information on the spread, persistence and ecological effect of the main crop species under review here and (b) developing models and decision support tools for the introduction of GM crops and their 
coexistence with other forms of cropping. SIGMEA has contributions from 45 partner 
organisations, and will be conducted over three years. Progress to date indicates that a very large part of the scientific knowledge on this topic is not yet in the public domain, because it is either recently comp leted and not published or is still in 
progress.   
 
• ECOGEN – Soil ecological and economic evaluation of genetically modified crops (
http://ecogen.dk ), an EC-funded project in progress, examining the effect of Bt 
maize and other biotech crops on soil communities and processes at field sites in Denmark and France. 
 
• The Farm Scale Evaluations of GMHT crops compared GMHT and conventional 
crop management on arable plants and invert ebrates at more than 250 sites in the UK. 
The first findings for spring-sown crops we re published in 2003 and the  effects of 
winter oilseed rape on biodiversity will be in 2004. Studies on gene movement and 
persistence of the GMHT trait are in progress.  
 
  The Farm Scale Evaluations of spring -sown genetically modified crops. 2003. 
Philosophical Transactions of the Royal Society, Biological Sciences, 358, Theme 
Issue. 
 
41. Botanical and rotational implications of geneti cally modified herbicide tolerance in winter 
oilseed rape and sugar beet (BRIGHT project). Several years of study at 5 sites in the UK comparing 
the management of various herbicide tolerant varieties.  
Final report at www.hgca.com  and look under Crop research . 
42. GMO Guidelines Project, under the auspices of th e International Organisation for Biological 
Control (IOBC), funded by the Swiss Development C ooperation; the aim is to  develop international  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  biosafety testing guidelines for transgenic pl ants, with emphasis on ecological communities and 
processes in developing countries, but in  principle applicable to Europe.  
Hillbeck A. and Andow DA (Eds) 2004. Environmental risk assessment of 
genetically modified organisms. Volume 1. A case study of Bt maize in Kenya. Eds. 
CAB International, Wallingford, UK.  Further case studies are in progress. 
43. Additionally, there are many other country-specific studies, notably in Germany, France, 
Denmark and the UK that are still in progress.  
44. In summary, the understanding of environmental and ecological risk and benefit has lagged 
behind the understanding of most other forms of risk . There is no set of agreed criteria for defining 
'ideal' arable ecosystems and this has restricted logical and rational argument on ecological impacts in 
most of the cases under review.  Research is in pr ogress in a range of European contexts to provide 
the scientific information which could be used to define the necessary criteria. 
Annex to Notes. Persistence and movement of genes among crops, weeds and wild relatives  
45. The summary in Table 1 is offered as background to  several of the panel's questions that refer 
to persistence and spread of GM plants. Several of the crops under re view have the potential to shed 
seed and leave descendents. The following definitions are used. Volunteer(s): plants that originate 
from seed or vegetative material shed or left by a crop and that inhabit fields, usually emerging as a 
weed within a crop. Feral: plants th at originate from seed or vegetative material shed or left by a crop 
and that exist outside fields, in waysides and the margins of agriculture. (Some authors use the term 
feral for plants descended from a crop whether they  are found inside or outside fields.) The table 
shows that transmission among crops, feral/volunteer  plants and wild relatives is highly species-
specific. Persistence and spread are generally greates t for oilseed rape, low for beet providing the crop 
is prevented from flowering, very low for maize ex cept between flowering maize crops and negligible 
for cotton as presently grown in EC countries. 
46. A relevant factor in all arguments over biotech oilseed rape is that the perception of oilseed 
rape as a weed pest in Europe has increased as mo re findings from research became available from the 
mid-1990s and through the early 2000s. Notable facts include – 
• It persists over 5 to 10 years at relatively high density in the soil (e.g. around 100 
seeds per square metre).  
• It is very widespread in the arable seedbank, commonly among the top 10 species 
within fields and occurs frequently as a wayside plant. 
• Its re-seeds in subsequent crops of oilseed rape. 
• Pollen-transfer causing low-frequency cr oss-pollination occurs over several 
kilometres: insect vectors are important in moving pollen. 
47. For the sake of balance, oilseed rape should also  be seen as a valuable and flexible 'break 
crop' in cereal rotations; it needs lower agrochemic al inputs than many other crops and  supports a 
high level of in-field biodiversity. WT/DS291/R/Add.6 
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  Table 1.  The ability of the crops to disperse genetic material through feral or 
volunteer progeny, pollen movement and out crossing to form hybrids in Europe. 
Author's summary.   
 Beet Maize Oilseed rape Cotton 
     
Feral / volunteer weeds 
 persistence in field 
 persistence outside field 
  
medium 
medium  
zero1 
low  
high 
medium 
  
zero 
zero 
Pollen transfer 
  crop to crop  
low2 
high  
high  
low 
  crop to feral /volunteer low2zero high zero 
  crop to wild relative low2zero low zero 
Crossing frequency (on arrival of pollen at flowering plants)     
 crop to crop  high high high low 
 crop to feral high zero1high - 
 crop to wild relative high (local) zero low - 
 
 1 In most of Europe; potential for some survival in the south. 
 2 Provided few or no crop plants allowed to flower. 
48. The presence of a GM construct should not markedly affect the qualities in Table 1 nor the 
status of oilseed rape and other crops as a weed. However, if the GM construct is accompanied by 
genes that make the plant more or less male-fertile than other sexually compatible plants, then the GM 
trait might be spread differentially. Oilseed rape can again be used as an example since it varies 
commonly in male fertility (i.e. the proportion of pl ants that produce pollen): in some crop varieties 
all (or nearly all) the plants are male fertile, but other varieties plants can be mixtures of male-fertile 
(20%) and male sterile (80%) individuals. Also, volunteers (including GM volunteers) produced from seed shed by some types of GMHT crop plant can be variously male fertile or male sterile. Generally, 
crops and plants that have more male sterility get more cross-pollination from other fields or plants 
than those that are fully fertile. It is importa nt to know when assessing the risk of spread and 
persistence whether the variety and its offspr ing are fully, partly or not male fertile. 
Dr. Snape  
49. The comments below relate to difficulties expe rienced by the Expert in provided a full 
exposition in answering questions No. 12, 16, 18 and 25, concerning the molecular characterisation of three exhibits, EC-062, EC-063 and EC-067.   
50. All the information on the molecular characterisation of a GMP (genetically modified plant) 
would greatly benefit from a summarisation and compilation into a single document for each exhibit. 
Currently, the evaluation of an exhibit requir es the mining of information in more than 100 
attachments often representing 1000 pages. Moreover, each attachment contains a mixture of 
information relative to different aspects of the risk assessment (transgene structure, expression, 
phenotypic stability, toxicity or allergenicity of the product etc. …). This greatly complicates the 
assessment and presents a significant risk that not a ll relevant information will be examined by each 
expert. This reviewer would recommend that all information relative to an exhibit is organised  WT/DS291/R/Add.6 
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  according to the structure of the EFSA-Q-2003- 005 guidance document Section III "Information 
required in applications for GM plants and/or deri ved food and feed". Data initially provided by the 
applicant as well as the subsequent questions and answ ers should be kept, by topic, in the appropriate 
part A, B, C or D of section III. This should allow experts in different fields to have a simplified and 
exhaustive access to the relevant information.  
51. This reviewer has some concerns about the criteria set by in the guidance document EFSA-Q-
2003-005 section III-D2 "information on the sequences actua lly inserted or deleted". The use of the 
term "insert" can be, and often has been in the e xhibits, a source of confusion. In some exhibits 
"insert" is understood and presented as the DNA sequence to be introduced, in others as the integrated 
transgenic coding sequence, in others as the integrated expression unit (promoter:coding sequence:polyA signal) and in others as the entire transg enic locus. In the past, this has led applicants 
to produce Southern blots and PCR-based analyses of  variable quality and information content. This 
has also led to a large number of subsequent request s for additional molecular information by experts. 
This situation could be avoided if  the information was initially requested in term of structural (and 
functional) analysis of each 
transgenic locus . A transgenic locus is here defined as a genetic location 
where transgenic sequences are linked (i.e. co-segrega ting at meiosis when integrated into the nucleus 
or remaining physically linked when part of other genetic structures). A transgenic locus can include 
some plant intervening DNA between transgenic sequences. Molecular analysis in terms of a 
transgenic locus is particularly rele vant for GM plants produced using Agrobacterium -based 
transformation technologies as they often contain transgenic sequences dispersed over several loci 
into the plant nuclear genome. Southern or PCR an alyses of multi-locus GM plants can be informative 
in terms of total copy numbers but have little relevance regarding the structural organisation of each transgenic locus (copy number, rearrangement level etc…). This Expert is of the opinion that the 
information required in section III-D2 should be re-organised as follows: 
 (1) Sub-cellular location of transgenic seque nces (nucleus, chloroplasts, mitochondria or 
maintained in a non-integrated form) [ same as part of section IIID2d in EFSA-Q-
2003-005]  
 (2) When transgenic sequences are inte grated into the nucleus, the number of 
independent transgenic loci. This is pr imarily obtained from inheritance pattern 
determined using the structural analysis of transgenic sequence(s) in progenies 
following appropriate self- or cross- pollination  [ similar to part of section IIID2d in 
EFSA-Q-2003-005 ]  
 (3) Information about each transgenic locus.  When more than one transgenic locus is 
present in the GM plant, the molecular ch aracterisation of each locus should be 
conducted independently when possible (i .e. when the GM plant is fertile). 
 
(a) The size and copy number of all detectable transgenic sequences, both 
complete and partial [ same as section IIID2a in EFSA-Q-2003-005 ] 
 
(b) The organisation of the transgenic seque nces at each transgenic locus and the 
methods used for characterisation [ same as section IIID2b in EFSA-Q-2003-
005] 
 
(c) In the case of deletion(s), size and f unction of the dele ted regions(s) [ same as 
section IIID2c in EFSA-Q-2003-005 ] 
 "Applicants should demonstrate ….. wh ich molecular analysis is but one" 
[same as section IIID2 in EFSA-Q-2003-005 ] 
 WT/DS291/R/Add.6 
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  (d) All sequence information including the location of primers used for detection 
[same as part of section IIID2e in EFSA-Q-2003-005 ]   
 "When events  have been combined by interbreeding ….. transformation event 
for risk assessment purposes" [ same as section IIID2 in EFSA-Q-2003-005 ] 
52. Please note that inheritance patterns based on the molecular analysis of transgenic sequences 
in progenies are rarely presented in the exhibits. Generally, the segregation of transgene phenotype 
(based on transgene expression in the progenies) is u sed to estimate inheritance pattern. However it is 
well documented in the literature that the segregati on of transgene phenotype is not always a reliable 
indicator of either transgene inheritance or transgene linkage as only expressing (i.e non-silenced) 
transgene copies are detected by expression studies. Th is is particularly relevant when monitoring the 
inheritance of non-functional transgenic sequences or when more than one copy  of the transgene(s) 
has been introduced into the plant genome. When a single transgene copy  is integrated into the plant 
nucleus, segregation studies based on transgene expr ession are satisfactory to estimate inheritance 
patterns.  
53. Please also note that the determination of genom ic flanking sequences is not enough in itself 
to ensure that no additional unw anted DNA sequences (such as antibiotic resistance genes from vector 
backbone) are present at a given transgen ic locus or overall in the genome. 
54. This Expert has some concerns about the cr iteria set by in the guidance document EFSA-Q-
2003-005 in sections III-D5 "Genetic stability of the insert and phenotypic stability of the GM plant". 
The current requirements are to "demonstrate the inheritance pattern and stability of the trait(s) introduced". This does not provide avenues to monitor potential recombination or deletion within a transgenic locus across generations. This point reiterates, as expressed in 2 a bove, the need to focus 
the molecular analysis at the tran sgenic locus level. It is documented that large, rearranged and 
complex transgenic loci such as those generated by  direct transfer of DNA (particle gun bombardment 
etc…) can be prone to such genetic rearrangement s across generations. A comparative Southern blot 
analysis of primary and some transgenic progeny plants using a selection of restriction digests and 
probes should be adequate to assess the structur al stability of each transgenic locus.  
55. Overall this Expert feels that the molecular ch aracterisation of the GM plants is probably one 
of the few areas where applicants have the oppor tunity to provide non-debatable and definitive 
information. This information can also be obtained using routine molecular techniques at a reasonable 
cost. In this context it is surprising that the opportu nity of providing a full molecular characterisation 
of GM plants is not always taken by the applican ts. In the case of a small transgenic locus (up to 
10,000 nucleotides) this Expert would even suggest  that applicants produce a full sequence of the 
transgenic locus. Most of the information n ecessary to produce an effective sequence is already 
required by EFSA-Q-2003-005 (genom ic flanking sequences, architecture of the transgenic locus 
determined by Southern blot analysis). This se quence of the transgenic locus and flanking plant 
genomic region along with a basic inheritance study at the structural level (using dot blot or PCR) and 
a Southern blot analysis of the primary tran sgenic plant and a few progenies should provide a 
compelling case for the molecular characterisation of each exhibit. When a single copy of each 
transgene is present in the GM plant at one locus,  this analysis can be simplified by using the 
segregation of transgene phenotype to estimate the i nheritance and stability of the transgenic locus. 
This reviewer understands that large and more co mplex transgenic loci, such as those produced by 
particle gun bombardment, may not be easy to sequence.  In this later case, particular attention should 
be given to the molecular stability of the transg enic locus structure over generation (see comment 3 
above).  WT/DS291/R/Add.6 
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  56. In conclusion I suggest: 
 1. The requests from the EC for informati on from the companies could have been more 
precise in its requirements, points 2 and 3 above. 
 2. The information collected by the EC co uld have been compiled more systematically, 
point 1 above. 
 3. Companies could have provided a full mol ecular characterization of the GM plants in 
the initial submissions, point 4 above.  
 
QUESTIONS TO EXPERTS  
General Questions 
 
Question 1:  On the basis of the information be fore the Panel, is there any scientific evidence to 
support the hypothesis that antibiotic resist ance marker genes (ARMG) pass from a biotech 
food or feed product to bacteria or other micro-o rganisms present in the human or animal gut?  
(a) If scientific evidence indicates that such an  event could occur, what risks, if any, 
would arise from that event?  What is the comparative relevance or magnitude 
of this risk in relation to the likelihood of such a transfer from other sources of antibiotic resistance not involving the use of recombinant DNA technology? 
(b) If such risks have been identified, what is the likelihood of adverse effects to 
human or animal health, in light of the processing of raw biotech products into 
human food or animal feedstuffs?   
(c) Are these consequences relevant to the specific types of ARMG currently used in the products at issue in this dispute? Please explain. 
(d) If such risks have been identified, what risk management options are available to 
mitigate those risks and what is their efficacy?  
Dr. Nutti  
57. According to FAO/WHO (2000), DNA transfer fro m plants to microbial or mammal cells, 
under normal circumstances of dietary exposure, woul d require all the following events to occur: 
(a) the relevant gene(s) would have to be released, probably as a linear fragment; 
(b) the gene(s) would have to survive nucleases in the plant and in the gastrointestinal 
tract;  
(c) the gene(s) would have to compete for uptake with dietary DNA; 
(d) the recipient bacteria or mammalian cells would have to be competent for 
transformation and the gene(s) would have to survive their restriction enzymes and 
(e) the gene(s) would have to be inserted in the host DNA by rare repair or recombinant 
events.  WT/DS291/R/Add.6 
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                                                       58. There have been numerous experiments aimed at evaluating the possibility of transfer of plant 
DNA to microbes and mammalian cells. To date, ther e are no reports that marker genes in plant DNA 
transfer to these cells.  Even so, the use of alternative transformation methods, which do not use 
ARMG, is encouraged. If alternative marker genes ar e used, they also must be evaluated regarding 
their safety. 
59. The transfer of marker genes which confer resistance to kanamycin, ampicillin and 
streptomycin to bacteria in the human gut is unlikely to present a significant health impact since 
bacteria resistant to these antibioti cs are already spread all over or are naturally found in the human 
gastrointestinal tract (S malla et al., 1993; Calva et al., 1996; Shaw et al., 1993; Smalla et al., 1997). 
Besides, kanamycin/neomycin and streptomycin ar e rarely used for humans due to their collateral 
effects (WHO 1993).2 
Question 2:  On the basis of the information be fore the Panel, is there any scientific evidence to 
support the hypothesis that antibiotic resistance develops through ways other than the uptake of 
food or feed by humans or animals, that is, due to the potential persistence of plant-derived DNA in the environment during crop cultivation and harvesting, and in soil residues?   
 
(a) If scientific evidence indicates that such an  event could occur, what risks, if any, 
would arise from that event?  What is the comparative relevance or magnitude of this risk in relation to the likelihood of such a transfer from other sources of 
antibiotic resistance not involving the use of recombinant DNA technology? 
(b) Are these consequences relevant to the specific types of ARMG currently used in 
the products at issue in this dispute? 
(c) If such risks have been identified, what risk management options are available to 
mitigate those risks and what is their efficacy ? 
Question 3:  On the basis of the information be fore the Panel, is there any scientific evidence to 
support the hypothesis that wide-spread cultivation of Bt crops such as biotech maize of the Bt 
variety adversely affects non-target organisms  which may be exposed to such crops under 
typical agricultural practice? (See, inter alia , EC-149, EC-150, EC-151, EC-152)  If so, how does 
this risk compare with risks to non-target organ isms arising from non-biotech applications for 
 
2 References: FAO/WHO. Safety asp ects of genetically modified foods of plant origin. Report of a 
Joint FAO/WHO Expert Consultation on Food Derived from Biotechnology, Geneva, Switzerland, 29 May-2 
June 2000. Rome: Food and Agriculture Organization of the United Nations. 2000. 
www.fao.org/es/esn/gm/biotec-e.htm
CALVA, J.J.; SIFUENTES-OSBORNIO,  J.; CERON, C. Antimicrobial resistance in fecal flora: 
longitudinal community-based surveillance of children from urban Mexico. Antimicrob. Agents Chemother., 
vol. 40, pp. 1699-1701, 1996. 
SHAW, K.J., RATHER, P.N., HARE, R.S. AND MILLER, G.H. Molecular genetics of 
aminoglycoside resistances genes and familial relationships of the aminoglycosidemodifying enzymes. Microbiol. Rev., vol. 57, pp. 138-163, 1993. 
SMALLA, K.; VAN OVERBEEK, L.S.; PUKALL, R.; VAN ELSAS, J.D. Prevalence of nptII and Tn5 
in kanamycin resistant bacteria from different environments. FEMS Microbiol. Ecol., vol. 13, pp. 47-58, 1993. 
SMALLA, K.; WELLINGTON, E.; VAN ELSAS, J.D. Natural background of bacterial antibiotic 
resistance genes in the environment. Nordic Seminar on Antibiotic Resistance Mark er Genes and Transgenic 
Plants, p 8-16. June 12-13, 1997, Oslo, Norway. The Norwegian Biotechnology Advisory Board. 
Workshop. World Health Organisation, Geneva.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  Bt toxins (i.e., the use of Bt toxin as an insecticide in conventional and organic farming)?  What 
risk management options are available to mitigate any resulting risks and what is their efficacy?  
Dr. Andow  
Scientific evidence:  
60. In the answer to this question, I will concentr ate on Bt maize and Bt cotton.  Yes. there is 
some scientific evidence to support the hypothesis th at wide-spread cultivation of Bt crops adversely 
affects non-target organisms which may be exposed to  such crops under typical agricultural practice.  
However, this evidence is insufficient to establish the hypothesis that such adverse effects are 
expected to occur. 
61. The review of non-target effects of Bt plants in EC -149 covered 13 laboratory studies 
evaluating potential hazard, and 14 field studies ai med at evaluating potential risk.  Of the 13 lab 
studies reviewed, I conclude that five studies did not  expose the test organisms properly and therefore 
are irrelevant hazard evaluations (an organism must be exposed to evaluate hazard).  In two additional 
studies, four of eight test species were not proper ly exposed.  Of the rema ining, seven species were 
studied.3  Of these seven, six were on Bt maize and none were on Bt cotton.  Bt toxin had significant 
adverse effects on two of these six species, the collembolan Folsomia candida (a soil organism) and 
the lacewing Chrysoperla carnea.  In neither case would adverse effects on these species been 
predicted based on the known spectrum of toxicity of  the Cry toxin.  There have been no studies to 
follow up the result with F. candida.  Hence, Dr. Andow concludes that there is a possible hazard 
(adverse effect) to collembola  from Cry1Ab Bt maize, but until this is confirmed, he cannot conclude 
that there is a potential risk to collembola.  Ther e have been numerous studies that confirm that C. 
carnea is somehow adversely affected by Cry1Ab toxin.4  Hence, he concludes that there is a 
potential risk to C. carnea  from Cry1Ab Bt maize. 
62. Of the 14 field studies reviewed in EC -149, six used plot sizes larger than 0.1 ha.5  Because 
most of the study organisms are mobile at spatia l scales much larger than the plot sizes used, it is 
necessary to have larger plot sizes and to tailor the sampling methods to detect possible transient 
differences in population sizes between treatments.  Otherwise, false negatives become problematic.  
The observed lack of significant differences between Bt and non-Bt treatments in nearly all the studies with small plot sizes is difficult to interpret, b ecause the absence of an observed difference in these 
kinds of experiments is not a good indication that there were no differences.  The only differences 
                                                      
3 Folsomia candida , Coleomegilla maculata , honey bee adults, Hippodamia convergens  adults, 2 
parasitoid species, Crysoperla carnea .   
4 Hilbeck, A., Baumgartner, M., Fried, P.M. & Bigler, F.  (1998a).  Effects of transgenic Bacillus 
thuringiensis corn-fed prey on mortality and development time of immature Chrysoperla carnea (Neuroptera: 
Chrysopidae). Environ. Entomol ., 27, 480-487.  Hilbeck, A., Moar, W.J., Pusztai-Carey, M., Filippini, A. & 
Bigler, F.  (1998b).  Toxicity of Bacillus thuringiensis Cry1Ab toxin to the predator Chrysoperla carnea. 
Environ. Entomol., 27, 1255-1263.  Hilbeck, A., Moar, W. J., Pusztai-Carey, M., Filippini, A. & Bigler, F.  
(1999).  Prey-mediated effects of Cry1Ab toxin and protoxin and Cry2A protoxin on the predator Chrysoperla 
carnea. Entomol. Exp. Appl., 91, 305-316.  Dutton, A. Klein, H., Romeis, J. & Bigler, F.  (2002).  Uptake o Bt-
toxin by herbivores feeding on transgenic maize and consequences for the predator Chrysoperla carnea.  Ecol. 
Entomol . 27, 441-447.  Dutton, A. Klein, H., Romeis, J. & Bigler, F.  (2003)  Prey-mediated effects of Bacillus 
thuringiensis spray on the predator Chrysoperla carnea .  Biol. Contr. 26, 209-215. 
5 Lozzia and Rigamonti 1998a. ATTI Giornate Fitopa tologiche, 223-228.  Lozzi a et al. 1998. Notiziario 
sulla Protezione delle plante 8: 27-39.  Lozzia and Rigamonti 1998b. IOBC Bulletin 21: 171-180.  Lozzia 1999. 
Boll. Zool. Agr. Bachic. Ser. II 31: 37-58.  Orr and Landi s. 1997. J. Econ. Entomol. 90: 905-909.  Hardee and 
Bryan 1997. J. Econ. Entomol. 90: 663-668. WT/DS291/R/Add.6 
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                                                       detected in these small plot studies were in the potato experiment,6 which will not be discussed here.  
Of the remaining six, two studies had insufficient replication.7  This low level of replication might 
allow the researchers to detect only differences larg er than an order of magnitude.  This detection 
threshold is much larger than what would be consider ed an adverse effect, so it is possible that some 
adverse effects were not detected.  The remaining f our studies had an equivalent of eight replications 
in each of two years.  No adverse effects were observed.  Unfortunately, the sampling methods were 
not sufficiently tailored to detect differences in population size.  Taken as a whole, excepting the 
results on Bt potato, the other 13 studies would indicate that very large, order of magnitude adverse 
effects on non-target species are unlikely.  However,  the data do not address the likelihood of other 
large adverse effects on non-target organisms.  Additional research would be needed before claims 
about safety can be supported with scientific evidence.  In particular, the cited field studies do not 
enable an evaluation of the likelihood of risk to C. carnea.  
63. EC-150 is a scientific paper that evaluated the effects of Bt maize litter (Bt11) on the 
earthworm Lumbricus terrestris in laboratory and semi-field experiments.8  There were no effects on 
survival or growth of immature earthworms in the semi-field experiment.  There were no difference in 
adult survival or growth during the first 160 days in the laboratory experiment.  Adults were about 
20% smaller with Bt litter than non-Bt litter at 200 da ys.  In total and compared with other published 
results, the results of this study indicate that adverse e ffects on L. terrestris, if they exist, are likely to 
be subtle.  In addition, they suggest that there is a possible hazard to earthworms  from Cry1Ab Bt 
maize litter, but until this is confirmed, the Expert cannot conclude that there is a potential risk to earthworms.   
64. EC-151 documents a novel route of exposure of soil organisms to Cry1Ab toxin from Bt 
maize.9  Cry1Ab toxin is exuded from living maize roots.  There has been some controversy as to 
whether the exudates are from damaged root cells  or from a process involving living root cells, 
however, the evidence suggests that th ere is a process involving living root cells.  This result was not 
anticipated.  Theoretically, the Cry1Ab protein w as considered too large to be exuded from living 
plant roots.  This study does not document a possible adverse effect of Bt maize , however, it 
demonstrates that species inhabiting the maize root rhizosphere can be exposed to Cry toxin.  This is 
significant because these species had been considered not at risk prev iously, and opens the possibility 
that unanticipated advserse effects to rhizoshere species might be identified. 
65. EC-152 demonstrates that Cry toxins persist, ac cumulate and remain insecticidal in soil by 
binding to humic acids in soils.10  Previous work had demonstrated similar results in binding to clay 
in soils.11  Moreover, the toxins maintain toxicity for at least 234 days (the longest time examined).12  
Together these studies demonstrate that Cry toxins w ill persist in soils much longer than previously 
believed, and that the mechanism of persistence is related to adsorption to clay particles and humic 
acids in the soil.  Together with EC-151, these studies demonstrate that soil organisms are likely to be exposed to Cry toxin via root exudates and litter.  None of these studies document a possible 
 
6 Riddick et al. 1998. Annals En tomol. Soc. Amer. 91: 647-653. 
7 Orr and Landis. 1997. J. Econ. Entomol. 90: 905-909 had 3 replications and conducted the experiment 
in only one year.  Hardee and Bryan 1997. J. Econ. Entomol. 90: 663-668 had 2 replications in each of two 
years. 
8 Zwahlen et al. 2003. Molecular Ecology 12: 1077-1086. 
9 Saxena et al. 1999. Nature 402: 480. 
10 Crecchio and Stotzky 1998. Soil Biol. Biochem. 30: 463-470. 
11 Venkateswerlu and Stotzky 1992. Current Microbiology 25: 1-9.  Tapp et al. 1994. Soil Biol. 
Biochem. 26: 663-679.  Tapp and Stotzky 1995a. Appl. Environ. Microbiol. 61: 602-609.  Tapp and Stotzky 1995b. Appl. Environ. Microbiol. 61: 1786-1790. 
12 Tapp and Stotzky 1998. Soil Biol. Biochem. 30: 471-476.  WT/DS291/R/Add.6 
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                                                       adverse effect of Bt maize .  Together, however, they suggest th at more species in the soil may be at 
risk than previously expected.  These results suggest  that additional studies may be needed to evaluate 
these possibilities. 
66. During 1999, concerns were expressed that m onarch butterflies would be adversely affected 
by Bt maize pollen falling on thei r host plant, common milkweed.13  This result was followed up with 
a series of studies to assess the risk to monarchs.14  The authors of these follow-up studies concluded 
that the risk to monarch populations was insigni ficant for Mon810 and Bt11, because only a small 
proportion of butterflies would be exposed to these and the toxicity of pollen was low.15  The events 
and findings associated with these studies ar e summarized in an excellent review.16  Recent studies,17 
however, have revealed a higher toxicity of Bt po llen and anthers than found in previous studies.  
Although some suggested that the risk to monarchs remains insignificant,18 a close reanalysis of the 
issues may allow other interpretations of risk to monarchs.   
67. Most these same papers also addressed the pot ential risk to monarchs from Event 176 BT 
maize.  Although they concluded that there was no risk to monarchs from Event 176,19 this was based 
largely on the assumption that Event 176 would not be used very much in production.  Had Event 176 
gained greater market share, it would likely have put monarchs at risk.20 
 
13 Losey et al. 1999. Nature 399: 214. 
14 Hellmich, R.L., Sigfried, B.D., Sears, M.K., Stan ley-Horn, D.E., Mattila, H.R., Spencer, T., Bidine, 
K.D., Daniels, M.J. & Lewis, L.C.  (2001).  Monarch larvae sensitivity to Bacillus thuringiensis -purified 
proteins and pollen. PNAS , 98, 11925-11930.  Oberhauser, K.S., Pr ypsby, M.D., Mattila, H.R., Stanley-Horn, 
D.E., Sears, M.K., Dively, G., Olson, E., Pleasants, J.M., Lam, W.-K.F. & Hellmich, R.L.  (2001).  Temporal 
and spatial overlap between monarch larvae and pollen.  PNAS, 98, 11913-11918.  Pleasants, J.M., Hellmich, R.L., Dively, G.P., Sears, M.K., Stanle y-Horn, D.E., Mattila, H.R., Foster, J.E., Clark, P. & Jones, G.D.  (2001).  
Corn pollen deposition on milkweeds in and near cornfiel ds.  PNAS, 98, 11919-11924.  Sears, M.K., Hellmich, 
R.L., Stanley-Horn, D.E., Oberhauser , K.S., Pleasants, J.M., Mattila, H.R., Siegried B.D. & Dively, G.P.  
(2001).  Impact of Bt corn pollen on monarch butterfly populations: a risk assessment.  PNAS, 98, 11937-11942.  
Stanley-Horn, D.E., Dively, G.P., He llmich, R.L., Mattila, H.R., Sears, M. K., Rose, R., Jesse, L.C.H., Losey, 
J.E., Obrycki, J.J. & Lewis, L.  (2001).  Assessing the impact of Cry1Ab-expressing corn pollen on monarch 
larvae in field studies.  PNAS, 98, 11931-11936. 
15 Sears, M.K., Hellmich, R.L., Stanley-Horn, D.E. , Oberhauser, K.S., Pleasants, J.M., Mattila, H.R., 
Siegried B.D. & Dively, G.P.  (2001).  Impact of Bt corn pollen on monarch butterfly populations: a risk 
assessment.  PNAS, 98, 11937-11942.   
16 Oberhauser, K.S. & Rivers, E.R.L.  (2003).  Monarch butterfly ( Danaus plexippus ) larvae and Bt 
maize pollen: a review of ecological ri sk assessment for a non-target species.  AgBiotechNet, 5, 1-7. 
17 Anderson, P.L., Hellmich, R.L., Sears, M.K., Sumerford, D.V. & Lewis, L.C. (2004).  Effects of 
Cry1Ab-expressing corn anthers on monarch butterfly larvae.  Environ. Entomol., 33, 1109-1115 .  Dively, G.P., 
Rose, R., Sears, M.K., Hellmich, R.L., Stanley-Horn, D.E ., Calvin, D.D., Russo, J.M. & Anderson, P.L.  (2004).  
Effects on monarch butterfly larvae (Lepidoptera: Danaid ae) after continuous exposu re to Cry1Ab-expressing 
corn during anthesis.  Environ. Entomol.,  33, 1116-1125.  Jesse, L.C.H. & Obrycki, J.J.  (2004).  Survival of 
experimental cohorts of monarch larvae following exposure to transgenic Bt corn pollen and anthers.  In: The 
monarch butterfly. biology and conservation (eds. Oberhauser, K.S., Solensky, M.J.).  Cornell University Press, 
Ithaca, pp. 69-75. 
18 Dively, G.P., Rose, R., Sears, M.K., Hellmich, R. L., Stanley-Horn, D.E., Calvin, D.D., Russo, J.M. 
& Anderson, P.L.  (2004).  Effects on monarch butterfly larvae (Lepidoptera: Danaidae) after continuous 
exposure to Cry1Ab-expressing corn during anthesis.  Environ. Entomol.,  33, 1116-1125.   
19 Sears, M.K., Hellmich, R.L., Stanley-Horn, D.E. , Oberhauser, K.S., Pleasants, J.M., Mattila, H.R., 
Siegried B.D. & Dively, G.P.  (2001).  Impact of Bt corn pollen on monarch butterfly populations: a risk 
assessment.  PNAS, 98, 11937-11942.   
20 NRC (National Research Council).  (2002).  Environmental effects of transgenic plants: the scope 
and adequacy of regulation . National Academies Press, Washington, DC, USA. WT/DS291/R/Add.6 
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  68. As mentioned in paragraph 61, C. carnea is under a potential risk from Bt maize.  Although 
this has not yet been studied in the field, Dr. Andow expects that the actual risk to C. carnea would 
not be large.  In maize in temperate regions, this species feeds primarily on aphids, mites, thrips, and 
lepidopteran eggs and larvae.  Previous studies ha ve shown that the main aphid on maize does not 
contain any Cry toxin when feeding on Bt maize, and that mites contain the Cry toxin, but they do not 
adversely affect C. carnea.  It is not known if thri ps or Lepidopteran eggs c ontain Cry toxin.  Adverse 
effects on C. carnea have been documented only when  it feeds on diets containing Cry toxin or on 
Lepidopteran larvae that had fed on Bt maize.  Any adverse effect from Lepidopteran larvae and 
possibly thrips and eggs would be diluted by feedi ng on aphids and mites.  Consequently, he believes 
that any adverse effect on C. carnea in the field w ill be subtle and difficult to detect in the field. 
69. Relatively few non-target studies have been conduc ted on Bt cotton.  This limits discussion of 
potential risks.  
70. It has been argued that the experience in using Bt maize and Bt cotton in the US provides 
evidence that there are no adverse effects on non-target organisms.  It  is true that Bt maize and Bt 
cotton have been used widely in the US, and it is also true that no adverse effects to non-target species 
have been reported and confirmed.  However, these two facts do not imply that there have been no 
adverse effects on non-target organisms, because th ere is virtually no monitoring for such adverse 
effects.  If such effects are not looked for, it is unlik ely that they will be found, even if they exist.  It 
can be reliably argued that the US experience w ith these crops suggests that there have been no 
immediate catastrophic adverse effects to non-target species.  Such catastrophes would have become noticeable even if they were not actively looked for.  However, it is more likely that adverse effects, if 
they exist, will be more subtle, and would not be readily noticed.  Hence, the US experience does not 
imply that there are no adverse effects on non-target species.  
71. In any event, Cry toxins are un likely to adversely affect mammals through direct toxicity.  
They exert their toxic effect by binding first w ith specific glycolipids in the gut.  These protein-
glycolipid complexes then bind to specific receptors (cadherin-like receptors) on the wall of the gut.  The entire family of the specific glycolipid and receptor molecules are absent from mammals, thus 
Cry toxins cannot act in their normal way in mammals.  
72. Conclusion.  Possible hazards have been identified and potential risks are evident, however, it 
cannot be concluded that an actual non-target risk of Bt maize or Bt cotton has been fully 
characterized.  However, it is likely that if the anal ysis is completed, that there will be a documented 
risk of some Bt maize events to monarch butterflies.   
Comparison with Bt insecticides:  
73. There are significant differences in exposure proba bility and exposure routes.  Bt insecticides 
have low likelihood of a non-target risk because they  do not persist very long after application.  The 
Cry toxin is degraded rapidly under UV light, and effi cacy of the insecticide is lost usually within a 
few days.  This contrasts with Bt crops, which produce Cry toxin constitutively over the entire 
growing season at high concentrations  throughout the plant tissue, and as noted above, can persist in 
the soil. 
74. It is theoretically possible that hazards will be different, but this depends on the protein 
structure of the Cry toxin in the plant compared with the insecticide.  For example, Event 176 Cry1Ab 
is significantly smaller than Cry1Ab toxin in the bacterium, Bacillus thuringiensis.  The full protein in 
the bacterium must be shortened to a form that show s active toxicity.  Event 176 protein is already in 
an active form.  Thus, if the shortening process a ffects hazards, then Event 176 protein may exhibit a  WT/DS291/R/Add.6 
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  different spectrum of hazards than the bacterium protein.  However, it has not been scientifically 
demonstrated that this difference in structure actually affects hazard.  There are also differences between Mon810 and Bt11 Cry1Ab and the Cry1Ab in  the bacterium.  There appears to be little 
difference between Event 1507 Cry1F and the Cry1F in the bacterium. 
75. Both are unlikely to adversely affect ma mmals.  The Bt insecticides have undergone 
significant number of studies on mammalian toxicity, a nd none have been found to be toxic to any of 
the mammals studied.  Coupled with paragraph 71, it is unlikely that either Bt crops or Bt insecticides 
will adversely effect mammals through direct toxicity. 
Risk management options : 
76. Risk management measures should be commensurate to the risk.21 
77. One risk management option is to prohibit the use of the Bt crop.  If this option is considered, 
it should be necessary to provide a worst-case risk ass essment to provide a basis for concluding that a 
prohibition is commensurate to the risk.  For example, what would be the harms if all earthworms 
were 20% smaller after feeding on Bt maize litter for more than 160 days (see paragraph 63)? 
78. Another approach would be to limit the area of the transgenic crop until a reasonable 
assessment of the possible hazards and potential risks are completed.  As the information is gathered, 
the risk management measure can be modified c onsistent with the principle of "modification."22 
79. For actual risks, such as the presumed risk to m onarchs, geographic restrictions in use of the 
Bt crop could be considered.  Incentives to use alternatives to the Bt crop can be provided.  
Disincentives for the use of the Bt crop could be imposed.  Monitoring of the population at risk could 
be required, although this would likely be more expensive than restricting or managing use, and may 
be difficult to justify based on the principle of equivalence.23 
80. Efforts to improve risk assessment procedures could be viewed as a form of risk management.  
Improved procedures24 would be more effective at identifying potential risk, reducing uncertainty and 
allowing risk assessment to proceed more rapidly. 
81. Another option would be to have no risk management.  Here it see ms necessary to have a risk 
assessment that concludes that there are no significan t non-target risks and that unanticipated effects 
will be either absent or insignificant. 
82. By no means should the Panel assume that this is an exhaustive list of possible management 
options.  These are suggestions of approaches to  risk management emphasizing avoiding risk.  
Approaches that emphasize mitigation of risk or tolerance of risk could also be considered. 
Dr. Squire  
83. Bt crops are grown widely in some regions of the world. They are used to target crop-specific 
pests, with a consequent, intended benefit that less chemical insecticide is used. They have a potential disadvantage, in that they might harm other organisms in the ecosystem. Among these are the 
                                                      
21 ISPM 11, 3.4. 
22 ISPM 11, 3.61. 
23 ISPM 11, 3.4. 
24 For example, Andow, D. A. & Hilbeck, A.  (2004).  Science-based risk assessment for non-target 
effects of transgenic crops .  BioScience, 54, 637-649. WT/DS291/R/Add.6 
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  predators and parasitoids that feed on the pests,  and organisms not normally reached by chemical 
insecticides. Important examples of the latter are soil fauna that might be exposed to the toxin if it 
occurs in or moves out of roots, and detritus feeder s and other decomposers that encounter the toxin in 
dead or dying plant matter. There are therefore arguable advantages and disadvantages in the use of 
the product. The emerging results from North Ameri ca show that pesticides have been reduced, but 
not in all instances – context is important. Much less information on non-target organisms has come 
from existing Bt maize-growing areas.  
84. Potential for ecosystem effects:  Assessments of potential ecological harm or benefit in areas 
such as Europe have so far relied largely on findings  from research in the laboratory or in contained 
systems in which the Bt plant and organisms tested have no, or restricted, contact with the outside 
world. Three of the exhibits referred to in Q.3 (EC-150, -151 and -152) are among this body of 
research. The potential for ecological effects is indicated by these and other studies, and some of them 
have shown that the toxin might well affect soil or ganisms. Exhibit EC-149 is a review of laboratory 
and field data up to 1999, and concludes that, be cause of the small area and short duration of the 
experiments, only limited inferences can be made a bout large scale or long term ecological effects. 
Since then, there have been few field-scale experime nts on Bt crops in Europe comparable to those in 
the present ECOGEN project, from which results should be available in 2005.  
85. Scaling, timescales and dilution. The publishe d studies do not demonstrate one way or the 
other what would happen if Bt maize were grown widely in Europe. There is no general consensus 
among scientists of what would happen when a Bt crop is introduced into any new region. It is argued 
by some that there could be a range of unforeseen, negative effects. In support of this view, the 
authors of Exhibit EC-149 write: 
Although such regulatory trials provide valuab le initial toxicity information, basing 
ecological assessments solely on bi-trophic feeding trials that provide the insecticidal 
protein in a highly processed form directly to the non-target organism is not 
sufficient. Ecologically important interactions between plants and herbivores and natural enemies/non-target organisms …. may be missed. 
86. The implication here is that exposure to the Bt plant over wider spatial zones, and season after 
season, might cause negative ecological effects that are not observed in short-term feeding trials in the 
laboratory or small-plot trials in the field.  
87. Conversely, it is argued that 'feeding' trials might create such artificial conditions, removing 
choice of food, etc. that they greatly overestimate effects that would occur in an ecosystem. An example of such a 'dilution' of effect is that of  the monarch butterfly in North America, for which 
damaging effects of Bt maize pollen, found in the laboratory, were subsequently shown unlikely to 
occur in the ecosystem. There were several reasons for this: much of the insect's food plant occurred 
outside Bt maize fields, the seasonal timing of the insect and the release of pollen only partly overlapped and the actual exposure of the insect to th e toxin was lower in maize fields than in the 
laboratory. A lay article Butterflies and Bt corn : allowing science to guide decisions, published by 
several US universities and the USDA provides a summary of the study; scientific papers are assembled in the journal Proc. Natl. Acad. Sci. USA,  vol. 98, 2001. The results of many other feeding 
experiments would similarly be 'diluted' (this review er believes) when examined in the context of the 
ecosystem. 
88. The general absence of ecological standards  and comparators. As discussed in the 
introductory notes, and in relation to herbicide-tolera nce (Q.6), a context and comparator are vital to 
any assessment, and as in the case of herbicide-tolerance, they have rarely been taken fully into  WT/DS291/R/Add.6 
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  account when assessing Bt crops. Assessments purporti ng to show harm, for instance, should compare 
the effects of the Bt crop with an existing practice or standard, such as current pesticide management, 
or options using application of Bt  preparations (for which there appears little ecological information). 
As for assessment of GMHT crops, there is no definiti on or set of criteria for an acceptable, resilient 
and sustainable ecosystem. It should be feasible for scientists to define such criteria, which would be 
generic but with location-specific elements. A recent case study of Bt maize in Kenya shows what can be done quickly by combining global and locati on-specific knowledge (Hilbeck A & Andow DA, eds. 
2004. Environmental risk assessment of genetically modified organisms. Vol 1, A case study of Bt 
maize in Kenya. CABI Publishing).  
89. Mitigation. It much more easy to confine maize within cropped fields than it is oilseed rape or 
beet, for example, so the ecological risks are mainly to do with the in-field food web and with any wide ranging organisms that visit the field (i.e. th ere are no risks in much of Europe through ferals 
and volunteers). To plan a mitigation strategy need s understanding of the existing state of the food 
web.  In the UK Farm Scale Evaluations (see Notes) , which used >60 fields of GMHT, not Bt, maize, 
the maize fields supported a small set of organisms compared to the organisms in oilseed rape and 
beet. This was so because the persistent herbicid es then used on maize sev erely reduced the arable 
plants available for the insects to eat. Moreover, only a few species in the above-ground food web were found on the maize itself. If maize is adopted over wide areas of a country where it had not been 
grown, that itself would affect biodiversity whether or  not it was Bt maize. Any additional effect of Bt 
should be seen in relation to the effect cause d by the introduction of maize as a crop species. 
However, if Bt maize was found to harm the in-field biodiversity, it should be feasible to reverse the 
effect by growing different crops in a rotation. Perh aps the main uncertainty is the effect of Bt maize 
on the soil food web. As indicated, the ECOGEN project should inform on this. Effects in the soil 
would be harder to monitor because it is very di fficult to assess soil biodiversity, particularly among 
bacteria and fungi.  Nevertheless, any adverse e ffects should be mitigatable through a rotation.  
90. Q.3 addresses a complex topic. The following is offered in summary.  
• The evidence is insufficient to  confirm whether widespread cultivation of Bt crops in 
Europe would affect non-target organisms. 
• The weight of evidence from contained expe riments and small-plot field experiments 
generally favours the view that little immediate toxic effect of Bt maize on the food web will occur in the field; but the eviden ce admits the possibility of chronic effects 
following long-term exposure to Bt maize. 
• The question could only be answered by long-term study of the effects of Bt maize and a comparator on the complex interacti ons among non-target organisms; it would 
be difficult to see how that would be done without intensely monitored, field-scale experimental plantings in Europe. 
• Criteria for resilient food webs would need to be proposed and agreed as a standard 
for any new research: without such criteria, progress is impossible. 
Question 4:  On the basis of the information be fore the Panel, is there any scientific evidence to 
support the hypothesis that the wide-spread cultivation of Bt maize or other, non-biotech applications of Bt toxins, leads to the emergen ce of Bt-resistant target organisms under field 
conditions? If so, what risk management options exist to mitigate any resulting risks and what is 
their efficacy?   WT/DS291/R/Add.6 
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  Dr. Andow  
91. Evidence for resistance.  Widespread non-biotech applications of Bt toxins have resulted in 
the Bt-resistant target pest organisms under field conditions.25  Probably the best studied example is 
diamondback moth on cabbage, which has developed fiel d resistance to Bt insecticide applications in 
several countries, including the US (Hawaii), Japan, Philippines and elsewhere.   
92. There is strong evidence that resistance will de velop in the field to any insecticide applied 
uniformly over wide areas for a long enough period of time.26  This has been a scientific consensus 
since the 1980s. 
93. Bt-resistant target organisms have been f ound – pink bollworm (Pectinophora gossypiella) to 
Bt cotton in the field,27 but this has not yet led to field failures.28 
94. Evolutionary theory predicts that the evol ution of resistance will proceed as directional 
selection, at least up to the point resistance becomes common.  This means that resistance in the field 
cannot be prevented, it can only be delayed. 
95. There is a scientific consensus that resistance to Bt maize is inevitable,29 even though it still 
has not been detected in the field.30  This is based on the preceding em pirical and theoretical evidence. 
96. Generally speaking, of all of the potential environmental risks of transgenic Bt crops, it can be 
said that resistance in the target pests is a real, ta ngible risk, while risks associated with gene flow and 
risks to non-target organisms are mostly only potential risks.   
97. There are several risk management options for Bt maize, but they are all concerned with 
reducing the selective advantage of resistant a lleles in populations of the target species.31 
98. The most widely used resistance management strategy for Bt maize (and all Bt crops) has 
been the high-dose/ refuge strategy.32  This has been used by th e US Environmental Protection 
                                                      
25 Tabashnik, B.E.  (1994).  Evolution of resistance to Bacillus thuringiensis .  Ann. Rev. Entomol., 39, 
47-79. 
26 NRC (National Research  Council).  (1986).  Pesticide resistance: strategies and tactics for 
management .  National Academy Press, Washington, DC. 
27 Tabashnik, B.E., Patin, A.L., Dennehy, T.J., Liu,  Y.B., Carrière, Y., Sims, M.A. & Antilla, L.  
(2000).  Frequency of resistance to Bacillus thuringiensis  in field populations of pink bollworm.  PNAS, 97, 
12980-12984. 
28 Tabashnik, B.E., Carrière, Y., Dennehy, T.J., Morin, S., Sisterson, M.S., Roush, R.T., Shelton, A.M. 
& Zhao J.-Z.  (2003).  Insect resistan ce to transgenic Bt crops: Lesson from the laboratory and field.  J. Econ. 
Entomol., 96, 1031-1038. 
29 Tabashnik, B.E.  (1994).  Evolution of resistance to Bacillus thuringiensis .  Ann. Rev. Entomol., 39, 
47-79.  Gould, F.  (1998).  Sustainability of transgen ic insecticidal cultivars: integrating pest genetics and 
ecology.  Ann. Rev. Ent., 43, 701-726.  Andow, D.A.  2001.  Resisting resistance to Bt corn, pp. 99-124.  In 
D.K. Letourneau and B.E. Burrows (eds.), Genetically engineered organisms: Assessing environmental and 
human health effects.  CRC Press, Boca Raton, FL. 
30 Bourguet, D., Chaufaux, J., Séguin M., Buisson, C ., Hinton, J.L., Stodola, T.J., Porter, P., Cronholm, 
G., Buschman, L.L. & Andow, D.A.  (2003).  Frequency of alleles conferring resistance to Bt maize in French 
and US corn belt populations of the European corn borer, Ostrinia nubilalis .  Theor. Appl. Genet., 106, 1225-
1233. 
31 Gould, F.  (1998).  Sustainability of transgenic insecticidal cultivars: integrating pest genetics and 
ecology.  Ann. Rev. Ent., 43, 701-726.  WT/DS291/R/Add.6 
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32 A major factor determining resistance management is the "dose" of the Bt crop.  Dose is defined as a 
concentration of Cry toxin in the Bt crop plant in relatio n to the expression of the resistance phenotypes.  For a 
high dose, the concentration of Cry toxin must be sufficie ntly high that the plant tissue is toxic enough so that 
resistance is functionally recessive (Fig. B1, concentration HD or higher, Taylor & Georghiou 1979; Tabashnik 
& Croft 1982).  Any other concentration is a low dose.  A high dose is desired for resistance management 
because resistance can be delayed more readily than fo r a low dose by using the high-dose/ refuge resistance 
management strategy.  A refuge is an area where the pest  is not subjected to selection from the Cry toxin and 
can produce a viable population.  The sa me crop plant without the Bt gene can function as a refuge as long as Bt 
insecticides are not applied to it.  Th ree conditions are essential to the success of the high-dose/ refuge strategy: 
resistance is recessive, resistance is rare, and there is sufficient intermating between adults coming from refuges 
and Bt fields.  
The recessivity of resistance is determined by complex interactions (Tabashnik & Croft 1982).  If 
resistance is determined by allelic variation at a single locus, with R designating the resistance allele and S the 
susceptible allele, dominance of the R allele is related to both the mechanism of resistance in the insect and the 
toxin concentration in the plant (Fig. 1, appendix to question) .  For example, if resistance in the insect is related 
to a change in a receptor in the midgut  lining, resistance may be physiologically recessive (Fig. 1a, appendix to 
question), while in other cases, the dose-mortality curve for RS heterozygotes may be physiologically co-
dominant (Fig. 1b, appendix to question) or dominant.  In both cases, the toxin concentration in the plant will 
also determine whether the R allele functions as a recessive allele ( HD in Fig 1a and 1b, appendix to question).  
If the concentration is not high enough relative to the dose-mortality curve for the RS heterozygote, the Bt crop 
would be a low dose crop.  Clearly, high dose cannot be  determined if resistance ha s not been observed in the 
target pest.   
Recessive resistance to Bt cotton (Cry1Ac) has been found in cotton budworm ( Heliothis virescens  
(F.), Gould et al. 1997, Gahan et al. 2001), cotton bollworm ( Helicoverpa armigera  (Hübner), Akhurst et al. 
2003) and pink bollworm ( Pectinophora gossypiella  (Saunders), Tabashnik et al. 2000), but no resistance has 
been found in cotton bollworm ( Helicoverpa zea  (Boddie)).  Resistance to Bt maize, which is the most widely 
grown Bt crop, has not been found in the widely distributed European corn borer ( Ostrinia nubilalis  (Hübner), 
Bourguet et al. 2003) or in southwestern corn borer ( Diatraea grandiosella  (Dyar)).  Resistance has been found 
in the beetle Chrysomela tremulae  F. to Bt poplar (Genissel et al., 2003), but not in rice stemborer ( Scirpophaga 
incertulas  (Walker), Bentur et al. 2000) to Bt rice.  Neither Bt poplar nor Bt rice is planted commercially at this 
time. 
There have been several attempts to designate a high dose without reference to a resistance allele, 
because the observed resistance alleles may not be the onl y ones and resistance has not been observed in some 
species.  The EPA-SAP (1998) has suggested that 25 times the the concentration of toxin at which 99% of the individuals in a susceptible population die (LC
99, lethal concentration 99) may function as a high dose.  Caprio 
et al. (2000) argue that 50 times the LC 99 is a better supported by the published data on insecticide resistance.  
The value of the EP A-SAP (or Caprio et al. 2000) standard is that it is readily operationalized for transgenic Bt 
crops.  The fundamental problem with this approach, however, is that it does not anticipate novel resistance 
mechanisms and may contribute a false sense of security  about the validity of the high-dose assumption.   
If resistance is recessive, it challenging to measure when rare.  As a rule of thumb, for the high-dose/ 
refuge strategy to be effective, the frequency of resi stance should be <0.001 (Roush & Miller 1986).  This 
implies that resistant phenotypes will be extremely rare, <1 x 10-6, and that more than 106 individuals from 
natural populations must be screened to estimate such low allele frequencies.   
Refuges are areas of habitat within normal dispersa l distance of the target species from a Bt habitat 
where the R and S alleles have similar fitness.  In addition, an effective refuge must be able to support a viable 
population of SS homozygotes in the tran sgenic landscape.  A refuge must be  within normal dispersal distances 
so that there is sufficient mixing and mating between individuals emerging in the refuge and Bt field.  A refuge 
can be any habitat where the target  species occurs, including the non- Bt crop, other crops, and other non-crop 
plants, as long as the R allele does not have a selective advantage in these fields.  If the refuge areas cannot 
support a viable population of SS homozygotes, then the population tends toward extinction, and there are insufficient SS individuals available to delay resistance evolution (Ives & Andow 2002).   
References cited.  Akhurst, R.J., James, W., Bird, L. & Beard, C.  (2003).  Resistance to the Cry1Ac δ-
endotoxin of Bacillus thuringiensis  in the cotton bollworm, Helicoverpa armigera  (Lepidoptera: Noctuidae).  J. 
Econ. Entomol., 96, 1290-1299. Bentur, J.S., Andow, D.A ., Cohen, M.B., Romena, A.M. & Gould, F.  (2000).  
Frequency of alleles conferring resistance to a Bacillus thuringiensis  toxin in a Philippine population of a rice WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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                                                                                                                                                                      Agency (US-EPA).  For Bt maize, it is generally accepted that a 20% refuge is needed for the high-
dose/ refuge strategy to be effective.33 
99. Low-dose Bt events will require a greater refuge.  There is no scientific consensus as to how 
big a refuge is needed.  One approach, used by the US-EPA is to require a 20% refuge during the 
initial period of use, when market penetration remains low.  This may provide enough time for the 
scientific evidence to accumulate so that an approp riate refuge size can be determined.  A different 
approach was used by Australia, where a very larg e refuge was required initially, which was gradually 
reduced over time to a 70% refuge. 
100. Additional resistance management strategies may become possible to develop after resistance 
in the target pest is identified and characterized.   
101. The efficacy of the high-dose/refuge strategy cannot be assessed empirically in the field.  
Indeed, it would probably be unethical to conduc t such a field experiment because it would be 
necessary to have a positive control treatment where resistance was encouraged .  Resistant insects in 
such a control treatment could escape, leading to field failures that undermine the efficacy of the high-
dose/ refuge strategy. 
 
stem borer, Scirpophaga incertulas  (Lepidoptera: Pyralidae).  J. Econ. Entomol., 93, 1515-1521. Bourguet, D., 
Chaufaux, J., Séguin, M., Buisson, C ., Hinton, J.L., Stodola, T.J., Porter, P., Cronholm, G., Buschman, L.L. & 
Andow, D.A.  (2003).  Frequency of alleles conferring resistance to Bt maize in French and US corn belt 
populations of the European corn borer, Ostrinia nubilalis .  Theor. Appl. Genet., 106, 1225-1233. Caprio, M.A., 
Sumerford, D.V. & Sims, S.R.  (2000).  Evaluating tran sgenic plants for suitability in pest and resistance 
management programs.  In: Field manual of techniques in invertebrate pathology  (eds. Lacey, L.A. & Kaya, 
H.K.).  Kluwer Academic Publishers, Amsterdam, pp. 805-828.  EPA-SAP (US Environmental Protection 
Agency – Scientific Advisory Panel).  (1998).  Transmitta l of the final report of the FIFRA Scientific Advisory 
Panel Subpanel on Bacillus thuringiensis (Bt) plant-pesticides and resistance management.  Meeting held on 
February 9-10, 1998. Report dated, April 28, 1998. (Docket Number: OPPTS-00231).  Gahan, L. J., Gould, F., 
& Heckel, D. G.  (2001).  Identification of  a gene associated with Bt resistance in Heliothis virescens .  Science, 
293, 857-860. Génissel, A., Augustin, S., Courtin, C., Pi late, G., Lorme, P. & Bourguet, D.  (2003).  Initial 
frequency of alleles conferring resistance to Bacillus thuringiensis  poplar in a field population of Chrysomela 
tremulae .  Proc. R. Soc. Ser. B.-Bio., 270, 791-797. Gould,  F., Anderson, A., Jones, A., Sumerford, D., Heckel, 
D.G., Lopez, J., Micinski, S., Leonard,  R. & Laster, M.  (1997).  Initial frequency of alleles for resistance to 
Bacillus thuringiensis  toxins in field populations of Heliothis virescens .  PNAS, 94, 3519-3523.  Ives, A.R. & 
Andow, D.A.  (2002).  Evolution of resistance to Bt crops: Directional selection in structured environments.  
Ecol. Lett., 5, 792-801. Roush, R.T. & Miller, G.L.  (1986).  Considerations for design of insecticide resistance 
monitoring programs.  J. Econ. Entomol., 79, 293-298. Tabashnik, B.E., Patin, A.L., Dennehy, T.J., Liu, Y.B., 
Carrière, Y., Sims, M.A. & Antilla, L.  (2000).  Frequency of resistance to Bacillus thuringiensis  in field 
populations of pink bollworm.  PNAS, 97, 12980-12984. Tabashnik, B.E. & Croft, B.A.  (1982).  Managing 
pesticide resistance in crop-arthropod complexes: Interactions between biological and operational factors.  
Environ. Entomol., 11, 1137-1144. Taylor, C.E. & Georghiou, G.P.  (1979).  Suppression of insecticide 
resistance by alteration of gene dominance and migration.  J. Econ. Entomol., 72, 105-109. 
33 EPA /US Environmental Protection Agency). (2001) .  Biopesticides registration action document – 
Bacillus thuringiensis  plant-incorporated protectants. 16 October 2001.  [WWW document] URL 
http://www.epa.gov/pesticides/biopesticides/pips/bt_brad.htm  (last accessed 23 November 2004).  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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                                                       102. Some greenhouse experiments have confirmed th e efficacy of the high-dose/refuge strategy.34 
103. Theory has predicted that the high-dose/ ref uge strategy will be efficacious when resistance 
allele frequency <0.001,35 resistance is recessive, and there is sufficient adult movement between the 
refuge and Bt fields to ensure matings between resistant and susceptible phenotypes. 
104. These assumptions have been confirmed scientifi cally for European corn borer (Ostrinia 
nubilalis) in the northern US corn belt.  These assumpti ons are likely for Europ ean corn borer in the 
southern US and in western Europe.  They have  not been confirmed for southwestern corn borer 
(Diatraea grandiosella) in the southern US, for European corn borer in eastern Europe, or for 
Mediterranean corn borer (Sesamia nonagrioides) in southern Europe.  Hence, it can be concluded 
that in some circumstances it is possible to predict that the high-dose/ refuge strategy should be 
efficacious.  It is possible that the absence of detec tion of field resistance to Bt maize in the US is 
partially attributed to the efficacy of the high-dose/ refuge strategy. 
 
34 Shelton, A.M., Tang, J.D., Roush, R.T, Metz, T.D. & Earle, E.D.  (2000).  Field tests on managing 
resistance to Bt engineered plants.  Nature Biotechnology, 18, 339-342. 
35 Roush, R.T. & Miller, G.L.  (1986 ).  Considerations for design of insecticide resistance monitoring 
programs.  J. Econ. Entomol., 79, 293-298. WT/DS291/R/Add.6 
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  Appendix  
 
Figure 1.  High dose (HD) and low dose (LD) concen trations (dotted vertical lines) in relation to 
hypothetical mortality of SS, SR, and RR insect genotypes as a function of Bt  crystal protein 
concentration (solid diagonal lines).  a. R allele is physiologically recessive, so SS and RS mortality is 
similar.  b. R allele confers an intermediate, co-dominant level of physiological resistance, so RS 
mortality is about midway between SS and RR mortality. 
 
 
SS RS
RR50% 90% 99% 
10% 
1% 
HD2 3 4 5 6 7 8 
-2 -1 0123  Mortality (probits)  
LDa. 
2 3 4 5 6 7 8 
-2 -1 0123  Concentration (log scale)Mortality (probits)  RS
HD LD LD SS RR50% 90% 99% 
10% 
1% b.  WT/DS291/R/Add.6 
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  Dr. Squire  
105. The emergence of resistance by pest insects to  pesticides differs widely from context to 
context depending on factors such as the exposure to and strength of the toxin, the movement of insect 
populations from areas where the pesticide is not applied, and the genetics and mating system of the 
insect. Resistance to Bt crops has occurred and is infl uenced by the 'dose' of toxin delivered to the 
pest and the genetic nature of the pest, among ot her factors. Because of long-standing scientific 
interest in pest resistance generally, knowledge has been imported from that body of work to construct 
models for the evolution and mitigation of Bt resi stance. The processes involved in Bt resistance and 
its management are generally appreciated by scientis ts, and mitigation strategies that have a strong 
scientific basis have been considered. By the la te 1990s, mathematical models of the population 
dynamics of resistant and susceptible biotypes were  being used to estimate the number of years for 
which the GM trait would remain effective in the f ace of genetic adaptation by the pest. The point is 
that sound scientific knowledge has been applied to this problem for several years.  
106. A strategy for mitigation needs protocols for both pre-emptive management, testing for 
resistance and managing it if found. The strategies mi ght involve providing refuges in or near the crop 
where resistant individuals do not have an advantag e over resistant ones, periodically controlling the 
pest by other means and growing different 'types' of Bt  maize, or Bt and non-Bt maize, either together 
or in sequence. Mitigation will be much easier to implement where the existing ethos is sympathetic 
to integrated pest management based on genetic and ecological principles. A useful, recent summary 
of the topic, much of it in layman's terms, directed at Bt maize in Kenya but based on generic arguments, is given by:  Fitt  GP et al., (2004). R esistance risks and management associated with Bt 
maize in Kenya. In Hilbeck A & Andow DA, eds. 2 004. Environmental risk assessment of genetically 
modified organisms. Vol 1, A case study of Bt maize in Kenya. CABI Publishing. 
Question 5:  On the basis of the information be fore the Panel, is there any scientific evidence to 
support the hypothesis that Bt maize varieties a re any more toxic to humans or animals than 
conventional maize under field conditions? If so, what risk management options exist to mitigate any resulting risks and what is their efficacy? 
Dr. Nutti  
107. Based on the information before the Panel, ther e is no evidence to support the hypothesis that 
Bt maize varieties are more toxic to humans or animals than conventional maize under field 
conditions. 
Dr. Squire  
108. (This response does not address the part of this question relating to humans.  Toxicity was 
considered as part of the Response to Q.3 and some  of the argument here is repeated.)  Assessing a 
product's toxicity to ecological processes is usually  more complicated than assessing the toxicity of, 
for example, a feedstuff for a domestic or farm an imal. The domestic or farm animal may have the 
food under test as its sole or main  diet in reality, whereas non-target  organisms genera lly have a wider 
choice of food throughout the habitat. Also, the ex pression of a toxin in a plant and its effect on 
animals eating the plant are influenced by local gr owing conditions, the weather, the behaviour or the 
local animals, etc., all of which differ between s ites. Therefore making inferences about toxicity to 
animals in one part of the world (e.g. a maize fi eld in a European country) from information in a 
constrained experiment, or field experience in anothe r part of the world, should be done with great 
caution.  The contention that nothing adverse has occurred when growing Bt maize in, say, North WT/DS291/R/Add.6 
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  America, should not be taken as definitive evidence by itself that nothing will occur in Europe, where 
the organisms and their interactions are different.  
109. Feeding experiments in which organisms are expos ed to live or dead Bt plant matter, and 
have no other choice of food, should be viewed as providing information only on the possibility that 
the Bt plant might be toxic to the animals in the fi eld. Many of the studies in contained experimental 
systems are of this type. Some do and others do not indicate harm occurred, but none should by 
themselves be taken to indicate that harm will nec essarily occur in the field. (Several major crop 
species would fail toxicity tests of this type.) Ma ny of the plot-scale experiments examined in EC-149 
were criticised by the authors of that review for a range of reasons, but taken as a whole, experiments at the scale of small field plots and one season's exposure indicate no acute toxicity to animals other than the pest.  
110. Evidence, either way, of harm to animals of growing Bt crops in the field in Europe is 
therefore inconclusive at present. The question could be approached by a range of experimental 
studies over longer periods, but the results would need  to be compared against the effects of other 
crop species on the animals, and against independent criteria defining a normal or healthy state for the 
animals in question (as for Q.3). 
Question 6:  On the basis of the information be fore the Panel, is there any scientific evidence to 
suggest that herbicide tolerant crops (whether biotech or developed through mutagenesis) are 
more persistent in the agricultural environment or more persistent in the non-agricultural 
environment than their conventional counterparts?  If so, do herbicide tolerant crops qualify as 
a potential "pest" as the term is used in the International Plant Convention's (IPPC) 
International Standard for Phytosanitary Measures (ISPM) 11 (EC-130)?  
(a) What is the potential for the establish ment and spread of herbicide tolerant 
plants arising from handling, spillage during transport of the plant/plant parts, 
or any other means outside of cultivation in the absence of application of the 
herbicide? How is any potential for establishment and spread affected by environmental conditions, the presences of wild or conventional relatives of the herbicide tolerant plants in an area, or other factors? 
(b) What is the potential for the establish ment and spread of herbicide tolerant 
plants in the presence of herbicide app lication (in fields, urban, domestic or 
other environments)?  How is any potential affected by the existence of feral related plant species; infertile wild relatives; seed survival in relevant pedoclimatic conditions; the reproduction biology of the species; or other factors? 
(c) Is this potential different for biotech crops tolerant to two wide-spectrum 
herbicides?  Please explain.  
(d) If significant risks of establishment and spread have been identified, what risk 
management options exist to mitigate any resulting risks and what is their efficacy? 
(e) What types of post-market monitoring and data collection activities could be envisaged on the basis of the monitori ng and review principles described in 
ISPM 11?  WT/DS291/R/Add.6 
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  Dr. Nutti  
111. According to the International Plant Conve ntion's (IPPC) International Standard for 
Phytosanitary Measures (ISPM) 11 (EC-130), the definition of pest is "Any species, strain or biotype 
of plant, animal or pathogenic agent injurious to plant or plant products".  In my opinion, herbicide 
tolerant crops can not be qualified as "pest", according to this definition. 
Dr. Andow  
112. I will provide a theoretical response to the ma in question and address only part (e) of the 
subparts of this question.  I will use the seven  kingdom taxonomy here and throughout in discussing 
organisms. 
113. Persistence of herbicide tolerant crops (wheth er biotech or developed through mutagenesis) 
will be determined by the relative fitness of the crop with the trait and the degree of release of the trait.  The only way that a GMHT would be more persistent than a non-GMHT  crop would be if it had 
a higher relative fitness and/or it was released at a higher rate.  Both factors would have to be assessed 
on a case-specific basis.  For GMHT maize, cotton,  soybean and beet, the question is moot because 
there are no comparably good non-GMHT varieties.   For GMHT oilseed rape, evidence from Canada 
suggests that the GMHT varieties are used more co mmonly than the non-GMHT varieties, thus there 
is some scientific evidence to suggest that GMHT  oilseed rape may be more persistent in the 
agricultural or non-agricultural environment th an their conventional HT oilseed rape.   
114. A similar argument holds for persistence of he rbicide tolerant crops (whether biotech or 
developed through mutagenesis) compared to thei r conventional counterparts.  When examining 
release rate, however, the relevant release rate for the conventional counterpart is that of a single 
variety. 
115. Annex 2 of ISPM 11 specifies "Phytosanitary ri sks from LMOs may result from certain traits 
introduced into the organism, such as those that in crease the potential for establishment and spread, or 
from inserted gene sequences that do not alter the pest characteristics of the organism by that might 
act independently of the organism or have uninten ded consequences."  Thus phytosanitary effects of 
the transgene outside of the original organi sm of introduction are covered by ISPM 11. 
116. Annex 2 elaborates on this further in the next clause, which states "In cases of phytosanitary 
risks related to gene flow, the LMO is acting more as a potential vector or pathway for introduction of 
a genetic construct of phytosanitary concern rather than as a pest in and of itself.  Therefore the term 
"pest" should be understood to include the potential of  an LMO to act as a vector or pathway for 
introduction of a gene presenting a potential phytosanita ry risk."  Phytosanitary risks associated with 
gene flow and persistence are covered by ISPM 11. 
117. Moreover, Annex 3 "Determining the potential for a living modified organism to be a pest", 
specifies that "potential phytosanitary risks fo r LMOs may include: a. Changes in adaptive 
characteristics which may increase the potential for introduction or spread, … b. Adverse effects of 
gene flow or gene transfer.  This indicates that th e potential for introduction and spread are a part of 
phytosanitary risk, as well as adverse effects of gene flow. 
118. From the perspective of gene flow and persistence, GMHT crops may qualify as a potential 
pest according to ISPM 11, as long as they can be sh own to be released at a higher rate and/or have a 
selective advantage compared to a conventional counterpart.   WT/DS291/R/Add.6 
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  119. Of course it is possible for a GMHT crop to qualify as a potential pest according to ISPM 11 
if persistence is expected to be the same as a conventional counterpart.  This would occur if it 
potentially resulted directly or indirectly in so me adverse effect that was different from the 
conventional counterpart.  For example, if contamin ation of conventional crop germplasm (related to 
the "coexistence" issue) were cons idered an injury to the conventi onal plant, then there would be a 
reason to believe that all GMHT crops can be c onsidered potential pests under ISPM 11.  All other 
potential pest risks would probably have to be considered on a case by case basis. 
120. ISPM 11 is ambiguous whether all possible e ffects of GMHT crops can be considered 
phytosanitary risks.  The definition of "pest" is given on page 6 of ISPM 11 as "Any species, strain or 
biotype of plant, animal or pathogenic agent injurious to plants or plant products [FAO, 1990; revised FAO, 1995; IPPC, 1997]"  The concept of "injurious to plants includes environmental risks, as indicated in supplementary text S1. 
121. Annex 2, which covers the scope of IPPC for LMOs states "PRA may constitute only a 
portion of the overall risk analysis for import and release of a LMO.  For example, countries may require the assessment of risks to human or animal health, or to the environment, beyond that covered 
by the IPPC."  This is a clear acknowledgement that  there are some environmental risks that are not 
covered by the IPPC. 
122. Annex 1 addresses the scope of the IPPC in regard to environmental risk.  This text is 
reproduced here: 
123. "The full range of pests covered by the IPPC  extends beyond pests directly affecting 
cultivated plants.  The coverage of the IPPC definition of plant pests includes weeds and other species that have indirect effects on plants, and the Conven tion applies to the protection of wild flora.  The 
scope of the IPPC also extends to organisms which are pests because they: 
– directly affect uncultivated/unmanaged plants  
 
124. Introduction of these pests may have few commercial consequences, and therefore they have 
been less likely to be evaluated, regulated and/or placed under official control.  An example of this 
type of pest is Dutch elm disease ( Ophiostoma novo-ulmi ). 
– indirectly affect plants 
 
125. In addition to pests that directly affect host pl ants, there are those, like most weeds/invasive 
plants, which affect plants primarily by other pro cesses such as competition (e.g . for cultivated plants:  
Canada thistle ( Cirsium arvense ) [weed of agricultural crops], or for uncultivated/unmanaged plants:  
Purple loosestrife ( Lythrum salicaria ) [competitor in natural and semi-natural habitats]). 
– indirectly affect plants through effects on other organisms 
 
126. Some pests may primarily affect other organi sms, but thereby cause deleterious effects on 
plant species, or plant health in habitats or ecosystems.  Examples include parasites of beneficial organisms, such as biological control agents. 
127. To protect the environment and biological di versity without creating disguised barriers to 
trade, environmental risks and risks to biologi cal diversity should be analyzed in a PRA."  WT/DS291/R/Add.6 
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  128. In considering indirect effects, Annex 1 a ddresses "indirect effects on plants" and "indirect 
effects on plant through effects on other organisms."  Indirect effects are not defined, but the two 
examples provided are two of the five fundamental  two-species interactions in ecological science, 
consumption (parasite-host or predator-prey or herb ivore-plant), competition, mutualism, amensalism, 
and commensalism.  Thus, indirect effects occur via any combination or pathway of these to-species 
interactions.  This is the standard interpretation of the concept of indi rect interactions which give rise 
to indirect effects in the field of ecology.  As the IPPC is science-based, I assume that standard scientific usage is appropriate for in terpreting key terms taken from science. 
129. Under this interpretation (and ot her interpretations as well), the effects of the herbicides 
applied to the GMHT crops is not covered under A nnex 1 and can not be considered a phytosanitary 
risk.  Herbicide use cannot be considered a direct  or indirect effect of the GMHT crop, because 
humans apply the herbicides.  It is inaccurate to say that this is an indirect effect of the GMHT crop 
through effects on other organisms.  The GMHT crop does not affect humans to apply herbicides.  
Causality works the other way.  Humans affect th e distribution of the GMHT crops and at the same 
time affect herbicide use.  Thus , the effects of herbicide use on GMHT crops is not covered under 
Annex 1. 
130. Section 2.3 of ISPM 11 covers "Assessment of potential economic consequences" and also 
covers environmental risk.  Under 2.3.1.2, indirect pest effects are considered.  This is a list of 
potential endpoints to consider given that it is an i ndirect effect.  Thus, section 2.3 does not provide an 
interpretation to cover the effects of herbicides applied to GMHT crops as a phytosanitary risk. 
131. It would be disingenuous to suggest that herb icide effects should be considered as if they 
were independent of the use of a GMHT crop.  While  it may be true that the environmental effects of 
herbicides are regulated under independent regulatory structures, this does not change the fact that 
they are used part and parcel with GMHT crops beca use that is their intended use.  Thus GMHT crops 
almost always will be accompanied by the use of the specific herbicide. 
132. The only ecologically consistent position would be  to identify humans as the potential pest.  
This, however, is absurd under ISPM 11. 
133. Thus I conclude that GMHT crops can qualify as a potential "pest" as the term is used in the 
International Plant Convention's (IPPC) Internationa l Standard for Phytosanitary Measures (ISPM) 11 
(EC-130).  However, not all of the risks associated with GMHT crops can be considered phytosanitary 
risks. 
(e) Post-market monitoring and data collection : 
134. Section 3.6.1 of ISPM 11 describes the monitoring and review of phytosanitary measures.  
This concentrates on the principle of "modification", and is repeated here. 
3.6.1 Monitoring and review of phytosanitary measures 
The principle of "modification" states:  "As conditions change, and as new facts 
become available, phytosanitary measures shall be modified promptly, either by inclusion of prohibitions, restrictions or requirements necessary for their success, or by removal of those found to be unnecessary" (ISPM N° 1:  Principles of plant 
quarantine as related to international trade ). WT/DS291/R/Add.6 
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  Thus, the implementation of particular  phytosanitary measures should not be 
considered to be permanent.  After app lication, the success of the measures in 
achieving their aim should be determined by monitoring during use.  This is often 
achieved by inspection of the commodity on arrival, noting any interceptions or any 
entries of the pest to the PRA area.  The information supporting the pest risk analysis 
should be periodically reviewed to ensure  that any new information that becomes 
available does not invalidate the decision taken. 
135. This suggests that an important part of th e risk management measures applied to GMHT 
crops should include a process to review the necessi ty of the management measures.  Given that many 
ecological effects are scale-dependent, manifesting more readily at larger spatial and temporal scales, some management measures could be linked to the sp atial extent of use of the GMHT crop.  If the 
spatial extent of use is not great enough, then certain management measures could be considered 
unnecessary.  Alternatively, if the GMHT trait persis ts in a given locality for long enough, additional 
management measures could become necessary. 
136. In a similar fashion, after certain time and area thresholds have been exceeded, it would be 
reasonable to review management measures to determin e if the measures need to be dropped, retained 
or strengthened.  Such thresholds should be agreed upon in advance.   
137. Finally, for precautionary management measur es, there should be certain time and area 
thresholds specified which would trigger a review to determine if sufficient information had 
accumulated to merit a reduction in the level of precaution.  Presumably the precautionary 
management measures would provide data from which it would be possible to assess their necessity. 
Dr. Snow  
138. Note: I use the terms herbicide resistance and herbicide tolerance interchangeably.  Weed 
scientists generally use the term resistance in this context to di stinguish between a newly evolved 
condition and an existing level of to lerance that has always been presen t.  Biotech companies prefer to 
use the term tolerant for transgenic crops that  have new genes for protection from herbicides. 
139. ISPM 11 definition of a pest (explained further in Annexes 1-3 of ISPM No. 11):  
• "Any species, strain, or biotype of plant. ... injurious to plants or plant products,"  
• "... many organisms indirectly affecting plan ts also satisfy this definition (such as 
weeds/invasive plants)" 
• Annex 3 mentions LMOs with increased pot ential for spread du e to ... "pesticide 
(including herbicide) resistance or tolerance" 
140. In summary, a crop with herbicide tolerance can qualify as a potential "pest" under the 
ISPM 11 definition if 1) it transmits herbicide resi stance to weedy volunteer plants or the crop's 
sexually-compatible wild relatives, and 2) this leads to worse weed problems.  Volunteer oilseed rape and its sexually-compatible relative, Brassica rapa, are considered to be w eeds because they compete 
with food crops and require management.  These plants  could become more abundant if they gain one 
or more types of herbicide resistance from the crop.  This can occur when the herbicide in question is 
used extensively (e.g., glyphosate) and herbicide-resistant volunteers become much more difficult to control.    WT/DS291/R/Add.6 
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  141. The magnitude of the problem, if and when th ere is a problem, depends on whether resistant 
volunteers and related weeds can be killed using othe r herbicides, crop rotation, and/or tilling, and on 
what amount of effort is needed to keep these plants from harming crop yields (e.g., Warwick et al. 
1999, Friesen et al. 2003).  This problem varies among species of crops and weeds that occur in 
different countries.  Brassica rapa is known to h ybridize with oilseed rape in Europe, but its 
abundance is usually kept under control by tilling and herbicide applications. 
142. I conclude that there is no evidence to suggest  that herbicide-resistant plants are more 
persistent in non-agricultural areas where herbicides are not used (e.g., Crawley et al. 2001), and there 
is no scientific reason to expect that this could ha ppen.  Also, each type of herbicide-tolerant crop 
should be considered individually – it is not possibl e to generalize across all herbicide-tolerant crops. 
143. ANSWERS 6a. and 6b:  Note: I assume that this question refers to plants that are cultivated 
by farmers, rather than seeds that ar e imported exclusively for processing. 
Routes of dispersal  
144. Seeds  – Genes for herbicide resistance, whether transgenes or not, can spread by means of 
seed movement.  Herbicide-tolerant crop plants can easily spread by seed dispersal that occurs during 
handling, transport, spillage.  Depending on the crop, seeds from volunteers, feral populations, and 
weedy relatives of the crop also disperse widely by wind, water, farm vehicles, and the transport of 
seeds, forage, and manure.   
145. Pollen  – Like other crop genes, transgenes for he rbicide tolerance can spread to sexually-
compatible crops and wild or weedy relatives that occur nearby by cross-pollination.  Therefore, the potential for spread and establishment of transgen es is greater when similar crops or wild/weedy 
relatives occur nearby.   
146. Pollen-mediated transfer of crop genes to ot her fields and to sexually-compatible wild 
relatives occurs more frequently in crops that typi cally cross-pollinate, such as maize and to a lesser 
extent oilseed rape, than in soybean, which is mostly  self-pollinated.  With respect to oilseed rape, the 
weed Brassica rapa is an obligate outcrosser that is known to hybridize with the crop (e.g., Jeorgensen 
and Andersen 1994). 
147. Transgenic tolerances to both glyphosate (Round-Up) and glufosinate (Liberty, Basta) are 
inherited as dominant, Mendelian traits.  Some transg enic varieties may have more than one insertions 
of a gene for herbicide tolerance, while others have just one.  A plant needs just one copy of the gene 
at one insertion site to be tolerant of the herbicid e in question.  This means that pollen from the crop 
can transfer the herbicide tolerance trait to seeds in other farmers' fields and to seeds of volunteer crop 
plants, related weeds, or wild relatives.  When different crop varieties have different genes for 
herbicide tolerance, weed populations can acquire sev eral types of herbicide resistance genes, as 
shown by Hall et al. (2001) for weedy, volunteer oilseed rape in Canada. 
Potential for establishment  
148. Some crops establish volunteer and feral populations more easily than others, depending 
largely on how thoroughly domesticated the crop is.  Oilseed rape is not highly domesticated in the 
sense that it can survive as free-living,  volunteer populations that can re-seed from year to year (e.g., 
Pessel et al. 2001).  Also, viable seeds of oilseed rape  can persist in the soil for several years, and then 
germinate and reproduce (Simard et al. 2002).  In contrast, maize does not establish feral populations WT/DS291/R/Add.6 
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  in Europe.  At most, maize plants can be present as volunteers in the year following the crop, but they 
do not establish problematic, long-term populations. 
149. Hybridization with sexually-compatible weed y relatives can further allow transgenes to 
spread and persist in and around agricultural fields.  Even when first-generation offspring between a 
crop and a weed are inferior to normal weeds, crop genes can often become incorporated into the local gene pool of the weed following further cross- pollination.  If progeny from these crosses are 
completely infertile, they will not produce seeds a nd they will not be a problem unless they establish 
clonal, vegetatively propagated populations, as in perennial grasses. 
Further spread after establishment  
150. Frequencies of specific crop genes in free-livi ng plant populations depend on their rates of 
introduction and also their effects on plant fitness (i.e, relative survival and reproduction). Unlike some types of nontransgenic herbicide tolerance, the transgenes that confer  tolerance to glyphosate 
and glufosinate are not expected to have any negative effects on crop yields or the fitness of crop 
relatives (e.g., Snow et al. 1998).   
151. In the absence of exposure to the herbicide in question, herbicide-tolerant plants will not have 
any selective advantage over their non-transgenic c ounterparts.  But when the herbicide is used 
repeatedly, it will select very quickly for plants that  are resistant to the herb icide.  The scientific 
literature in weed science is full of examples of rapid evolution and spread of herbicide resistant 
weeds (e.g., Warwick et al. 1999, WSSA 2005).  
152. ANSWER 6c:  In principal, the potential for the establishment and spread of herbicide-
tolerant plants is similar for nontransgenic vs. transgenic crops that have genes for these traits.  Rates 
of establishment and spread of herbicide-tolera nt crops are affected by whether the genes for 
herbicide resistance show dominant or recessive inheritance, whether the resistance genes are 
associated with fitness costs (i.e., re duced survival or reproduction), and the extent to which the plants 
are exposed to the herbicide(s) in question.  Transgenes that confer resistance to glyphosate or glufosinate show dominant inheritance and they are not  likely to be associated with fitness costs (e.g., 
Snow et al. 1998). 
153. In answers 6a and 6b, I discuss how biotech crops with resistance to either of these two wide-
spectrum herbicides might contribute to the spread and establishment of herbicide-resistant weeds.  
This can happen by gene flow to related weeds,  and also by another mechanism – spontaneous 
selection for weeds that are naturally resistant to  the herbicide.  The second mechanism has occurred 
in only a few species for the two herbicides in que stion.  Once a gene for glyphosate or glufosinate 
resistance is present, is likely to increase in fre quency in compatible weeds and volunteer populations 
that are exposed to these herbicides.  The more the herbicide is used, the stronger the selection 
pressure favoring herbicide-resistant weeds.  Gly phosate use is already common and is expected to 
increase further when crops are bred to have transgenic resistance to this herbicide.  Glyphosate is very useful to farmers because it is wide-spectrum, killing most weed species very efficiently, and it is considered to be "environmentally friendly", as compared  to other herbicides.  Glufosinate is used less 
widely, but its use also is expected to increase afte r biotech crops with glufosinate tolerance have been 
commercialized.  
154. ANSWER 6d:  Several risk management options ar e available to mitigate problems that result 
from plant pest populations that are tolerant of one or more herbicides, but they may or may not be 
very practical (e.g., Beckie et al. 2004, Devos et al. 2005).  One way to prevent herbicide-tolerant 
weeds from becoming more abundant is to rotate among herbicides with different modes of action  WT/DS291/R/Add.6 
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  from one year to the next, in a cycle that accounts for the persistence of viable seeds of herbicide-
resistant weeds in the soil.   
155. Another method for suppressing populations of herbicide-resistant weeds is to use several 
types of herbicides in tank-mixes each year, before or after a crop is grown, to kill off resistant plants.  
Management options become more challenging and more complicated when the pest population has 
genes for several types of herbicid e resistance.  In some cases, it ma y be necessary to revert to the use 
of herbicides that have greater toxicity and longer persistence in the environment (e.g., 2,4-D). 
156. The efficacy of different management options will vary depending on local conditions and the 
types of crops and rotation systems that are used.  For oilseed rape, which has a long-lived seed bank, 
seeds of weedy volunteer plants may emerge over a period of at least 4-5 years (Simard et al. 2002). 
157. As mentioned above, it is expected that transgenes that confer herbicide tolerance will not be 
associated with negative effects on the weedy plants that inherit them.  This me ans that the transgenes 
could persist indefinitely in weed populations, ev en in the absence of exposure to herbicides.   
158. ANSWER 6e:  In cases where the persistence and proliferation of herbicide-resistant weeds 
could pose problems, post-market monitoring could be  used to develop an early warning system for 
alleviating the problem.  Weed scientists are already acutely aware of emerging problems with 
herbicide-resistant weeds that develop in response to heavy herbicide use (e.g., WSSA 2005).  Many farmers are also familiar with these problems.  Stewardship programs can be developed for risk management, for example by encouraging farmers to  report cases of herbicide failure to the proper 
authorities. Studies of reported cases could be carried out  to test for resistance due to transgenes, and 
to determine whether the stewardship programs are working as planned.   
159. However, by the time the spread of herbicide resistance is detected in free-living pest 
populations, such as weeds or volunteer plants, it may be too late to prevent these plants from 
proliferating further.  By this time, continuous e fforts may be needed to keep their populations as low 
as possible.  After a transgene for glyphosate has spread widely in oilseed rape, as occurred in 
Canada, there is no easy way to eliminate the problem. 
Dr. Squire  
160. The background to this question is that several of the crops have become widespread feral 
plants or weeds (see Notes, Annex). Oilseed rape has been grown in Europe for centuries, but has 
become a weed in many parts of Europe following  a great increase in its cropped area since the 1970s. 
It is now a regular and persistent member of th e arable and wayside seedbank (buried viable seeds). 
Oilseed rape is not considered a problem on waysid es and is ousted by perennial vegetation such as 
grass. Within fields, it is treated as part of the broadl eaf weed flora. It also contributes to yield of the 
next oilseed rape crop, but has generally not been  considered a problem in this respect, since the 
quality of oil has generally been similar in the volun teers and crop plants. Similarly weed beet, arising 
from seeding crop beet, is common in beet-growing areas and brings similar but lesser problems.  
161. Are HT plants a potential pest? Oilseed rape and beet are both crops and pests, as are many 
other crop plants (pests as defined in ISPM-11, pa ge 6). The volunteers or ferals arising from HT 
crops would be no greater pests than those arising from non-HT crops, unless the specific herbicide was used to favour them as pests, or their presence in the field or in the yield itself had greater significance than the presence of non-HT. Since agriculture began, crops and weeds of the same 
species have existed side by side and exchanges ge nes – but this does not mean that volunteer/feral 
weeds are not pests.  WT/DS291/R/Add.6 
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  162. More serious problems to do with their persiste nce as pests will arise if labelling or marketing 
'rules' specified that a non-biotech crop had to be of a high degree of purity, i.e. to contain less than, 
say, 0.9% of GM in the yield. 
163. 6a. In the absence of use of the specific herbicide, HT plants would have the same potential as 
non-HT, as indicated in 6 above. Species would diffe r as in Table 1. Establishment and spread 
depends on local conditions in ways that are not clear. For example, feral wayside populations of 
oilseed rape differ greatly in number in areas st udied in France and the UK. Also, wild, weedy 
relatives differ in their presence and number in different parts of Europe, as do hybridisation rates 
between crops and between cr ops and wild relatives.  But the essen tial point is that – in the absence of 
the specific herbicide to which the plants are tolera nt – plants having HT and non-HT traits should act 
similarly.  
164. 6b. Suppose that HT plants were growing in mixed vegetation with non-HT plants of the 
same and other species, then applying the herbicide would favour the HT plants, lead to greater seed 
set on HT plants and their increase in the seedbank.  This would happen wherever the plants were 
growing and whether the HT trait was in volunteer/ feral plants of had been transferred to wild 
relatives. Whether such differences  occurred in practice would then depend on the how widely the 
specific herbicides were used (which itself would vary between countries and crops).  
165. 6c. In the absence of the specific herbicide, the potential for establishment and spread should 
be similar for biotech plants tolerant to the wide-spectrum herbicides glufosinate ammonium and glyphosate. The genes conferring tolerance to either s hould not enable the plants to be better at, say, 
persisting in the soil. Relative persistence between the two GMHT types would differ if one or both of 
the herbicides was used. As indicated, this will be hi ghly specific to the agronomy of a farm or region. 
For instance, in the UK, glyphosate has risen in the last few years to be the second (or maybe first) 
most widely applied herbicide in arable fields, while glufosinate ammonium is used little in fields or waysides. If GMHT glyphosate tolerant plants were present in fields, then they would be advantaged 
at this specific time and area, where glufos inate ammonium tolerant plants would not.  
166. 6d. Risk management options should be similar to those recommended for non-biotech 
varieties (oilseed rape and beet), but would need to  be more stringently applied if cropping was to 
ensure the proportion of GM in non-GM remained be low a threshold.  Establishment can be reduced 
by –  
• Reducing or preventing seed loss to the soil, e. g. by harvesting oilseed rape before too 
many pods split (not always possible) , uprooting flowering beet plants.  
• Not cultivating soil after harvest, leaving seeds to germinate on soil and then killing 
them by cultivation or herbicide spray. 
• As part of normal broadleaf weed control, ensure they do not flower and seed in later 
crops of other species.  
• Spread can be reduced by – 
• Clearing seed from combine harvesters and other machinery between crops. 
• Transporting seed from field to market in sealed containers or vehicles. 
• Cutting or spraying roadsides that support la rge populations of feral oilseed rape, but 
these practices will impinge on the semi-natural flora. 
• Using a pollen barrier to reduce field-to-fiel d geneflow (oilseed rape and maize), such 
as a strip of flowering crop 50 to 100 m wide between the donor and recipient crops and which is not harvested as part of the recipient crop.  WT/DS291/R/Add.6 
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  167. The main difficulty in preventing establishment and spread is with oilseed rape, specifically 
in that it will enter the soil and become dormant ev en if soil is not cultivated after harvest, it will 
flower and seed, usually unseen, in a later crop of oil seed rape and it is impractical to remove all seed 
from farm machinery. Lesser pr oblems occur with weed beet. 
168. 6e. Post-market monitoring:  ISPM 11 does not give great detail on monitoring. The type of 
monitoring in this instance would differ depending on purpose: for example, monitoring the effect of 
a HT cropping on biodiversity or ecosystem f unctioning would require a different set of 
measurements from monitoring the presence or abundance of a HT trait. What is clear from existing 
data and work in progress is that monitoring of this  type is far from simple and needs much time and 
effort, especially if the aim to measure low frequenci es (e.g. 1%, 0.1%) or small effects (e.g. 1.5-fold 
effects on populations or ecological processes). Recently introduced populations are highly 
aggregated or clumped and this increases the number of samples and area over which samples have to 
be taken. At present, there are no reliable and accepted monitoring schemes for the presence or impact 
of biotech-derived plants: research is in progress to develop such schemes (see Notes, paragraph 14), 
but it is not even certain that it would be feasibl e or practicable to monitor low frequency occurrences 
or ecological effects routinely in the field. 
Question 7:  On the basis of the information be fore the Panel, is there any scientific evidence to 
support the hypothesis that repeated use of a given biotech herbicide tolerant crop has adverse effects on flora and fauna, including soil micro - and macro-fauna? If so, how does this compare 
with any similar risks of adverse effects from the repeated use of a non-biotech herbicide tolerant crop (i.e, one developed through mutagenesis)? 
Dr. Andow  
169. I will restrict this answer to the following ge netically modified herbicide tolerant (GMHT) 
crops:  oilseed rape, fodder beet, cotton, maize, so ybean, and sugar beet.  I will use the seven kingdom 
taxonomy in discussing organisms. 
Adverse Effects of GMHT Crops : 
170. There is abundant evidence that repeated use of  a given biotech herbicide tolerant crop would 
likely result in the evolution of resistance in weeds to  the herbicide.  While it can be debated if this 
adverse effect results from repeated use of the GM HT crop or from the repeated use of the herbicide 
of which the GMHT crop is tolerant, in practice th e two are so tightly correlated, and the GMHT crop 
is expected to have the herbicide applied to it.  Hence a risk assessment should consider both as correlated causal factors.  In the la nguage before the panel, weed resi stance is a risk resulting from the 
associated changes in agricultural practices. 
171. Adverse effects on non-target flora and fauna could arise directly from transgene products, 
directly from the herbicide compounds, or indirectly through the effects of the transgenic crop or the 
herbicide on the environment.  Although the author s of the Farm-Scale Evaluation (FSE) Trials of 
GMHT crops in the UK36 concluded that all adverse non-target e ffects arise indirectly from the effects 
                                                      
36 Brooks et al. 2003, Phil. Trans. R. Soc. Lond. B, 358, 1847-1862.  Champion et al. 2003, Phil. Trans. 
R. Soc. Lond.  B, 358, 1801-1818.  Firbank 2003, Phil. Trans. R.  Soc. Lond. B, 358, 1777-1778.  Haughton et al. 
2003, Phil. Trans. R. Soc. Lond. B, 358, 1863-1877.  Ha wes et al. 2003, Phil. Trans. R. Soc. Lond. B, 1899-
1913.  Heard et al. 2003, Phil. Trans. R. Soc. Lond. B, 358, 1819-1832.  Hear d et al. 2003, Trans. R. Soc. Lond. 
B, 358, 1833-1846.  Roy et al. 2003, Phil. Trans. R. Soc. Lond. B, 358, 1879-1898.  Squire et al. 2003, Phil. 
Trans. R. Soc. Lond. B, 358, 1779-1799. WT/DS291/R/Add.6 
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  of the herbicide on the environment,37 this highly credible argument is not proved conclusively.38  In 
any event, the FSE Trials demonstrate that some, but not all, GMHT crops can have adverse effects 
on non-target organisms.  I believe that it is likely that additional adverse effects on non-target 
organisms may be reported in the future. 
172. Gene flow from a GMHT crop to a weedy relative can create weeds that are more difficult to 
control with herbicides.  This occurred for GMHT oilseed rape in Canada.  GMHT maize, cotton and 
soybean have not yet been grown legally in loca tions where there are weedy relatives and none occur 
in Europe, the US, Canada or Argentina, so this risk is not possible in these countries.  Beets have 
wild relatives in Europe, and weedy beets have developed as a consequence of gene flow in the past.   
173. Gene flow from a GMHT crop to another crop cultivar can contaminate seed supplies (part of 
the "coexistence" issue) or reduce genetic diversity in the crop.  Contamination is a serious concern, 
although it can be debated if this adve rse effect is on the flora (the crop) or the growers of the crop.  It 
is clear that the harm is to the growers of the crop.  Genetic diversity of cotton, maize and soybean is 
not known to be great in Europe, so this is unlikely to be a concern.  It may be possible that there are 
significant sources of genetic diversity in oilseed rape and beets in Europe.   
174. To my knowledge there are no reports of adverse effects on soil micro- or macro-flora or 
fauna separate from those in the UK-FSE trials.  Nor are there any reports of adverse effects on soil 
dwelling bacteria, algae, or protozoa.  However, to my knowledge there have not been any studies of 
any of these possible effects.  The Panel should not infer that the absence of information implies an 
absence of effect. 
175. To my knowledge, all reports have not found adverse effects on flora or fauna from antibiotic 
resistance genes or gene products.  Extensive st udies on nptII did not find any adverse effects, and 
found that any undetected adverse effects would like ly be several orders of magnitude smaller than 
naturally occurring phenomena. 
Comparison with non-GM HT Crops : 
176. There are several ways in which GMHT and non-GMHT crops may differ that are significant 
to risk to flora and fauna. 
177. GMHT traits are typically hemizygous, which means that there is only one copy of the locus 
in the plant.  Normal plant genes occur in two copies, that are either different (heterozygous) or the 
same (homozygous).  Gene flow to wild relatives or  other crop varieties will result in hemizygous 
offspring for GMHT traits, which are likely to ex hibit dominant expression.  For non-GMHT traits, 
hybrid offspring are most likely to be heterozygo us and may exhibit varying degrees of dominance.  
This means that whatever the selective advantage of the trait in the original HT plant, it is likely to be 
similar for GMHT hybrids, but possibly less for non- GMHT hybrids.  Because selective advantage is 
one of key determinants of spread of genes, this would suggest that GMHT traits could be more likely 
to spread than equivalent non-GMHT traits.39 
178. The promoters on most GMHT transgenes keep th e transgene turned on and expressing at all 
times.  The non-GMHT transgenes are regulated by plant promoters, which may or may not keep the 
                                                      
37 Champion et al. 2003, Phil.  Trans. R. Soc. Lond.  B, 358, 1801-1818.   
38 Andow 2003, Nature Biotechnology, 21, 1453-1454.   
39 It should be recognized that while the bits of information that comprise this argument can be found in 
the information before the Panel, the argument itself ca nnot be found in the information before the Panel.  WT/DS291/R/Add.6 
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  gene turned on all the time.  This may enable the herbicide to be used for a longer period of time on 
the GMHT crop than the non-GMHT crop.  If so, gr eater degrees of weed reduction may be possible 
in GMHT than non-GMHT crops, which would r esult in greater non-target effects and higher 
selection for weed resistance in more species of weeds.40 
179. Most of the GMHT crops tolerate glufosinat e and glyphosate, while most of the non-GMHT 
crops tolerate imidazolinone and sulfonylurea herbic ides.  It is possible that there are important 
differences in these herbicides that result in different risks to flora and fauna.  I am unaware of studies 
that address this possibility.  In addition, the opti ons for managing resistant weeds are likely to differ 
among the different herbicides. 
180. Scale of use has a significant effect on risk.41  Some GMHT crops have gained significant 
spatial scales of use that dwarf those of  non-GMHT crops.  For example, RoundUp Ready® soybean 
now occupies >60 of the US soybean area (>20 million hectares), while no non-GMHT trait has come close.  With greater scale, small effects can reinforce each other and become more apparent.  This 
would be especially true for non-target effect s, such as those found in the FSE trials. 
181. If contamination is an adverse effect on flor a, then GMHT crops have this risk while non-
GMHT crops do not.  This is based on the definition of harm, which is premised on distinguishing 
between GM and non-GM traits. 
182. If all of the factors mentioned in paragraphs 177 through 181 are equivalent between the 
GMHT and non-GMHT crop, then there will be no pred icted difference in the risks of adverse effects 
from the repeated use of a GMHT or non-GMHT crop. 
Dr. Squire  
183. The difficulties of argument in this topic revolve around what is classed as an adverse effect 
(Notes, paragraphs 32-35). There are no objective criteria for what is an ideal state and what therefore 
might be judged an adverse effect against that stat e. At best, HT cropping has been compared against 
an existing cropping system. Certainly in Europe, the important and relevant  flora and fauna should 
include those within the managed areas of fields.  
184. The Farm Scale Evaluations (FSE) in the UK (Notes, paragraph 14) detected small, but 
important shifts caused by using GMHT rather than the conventional management, and illustrate 
issues of context. The difference in weed management  rather than the GM or conventional crop plants 
per se was the effective agent. The direction of effect differed depending on the severity of the 
conventional management. In maize, where convent ional management uses pe rsistent, highly toxic 
herbicides, GMHT increased the flora and fauna; in spring oilseed rape and beet, where current 
practice was less effective against arable plants, it had the opposite effect, reducing the flora and 
fauna. The crucial point about the FSE – and one that  has been missed or misrepresented by many 
international commentators – is that the effects on the arable flora or weeds (though small by 
international standards) were important in the context of the UK's arable scene in the early 21st 
century. The flora and fauna of arable fields were important in the national biodiversity as perceived 
by many people; these flora and fauna had already b een severely depleted by intense agriculture, so 
further depletion was unnecessary and unacceptable.  
                                                      
40 It should be recognized that while the bits of information that comprise this argument can be found in 
the information before the Panel, the argument itself ca nnot be found in the information before the Panel. 
41 NRC (National Research  Council).  (1987).  Introduction of recombinant DNA-engineered 
organisms into the environment: key issues.   National Academy Press, Washington, D.C. WT/DS291/R/Add.6 
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  185. In principle, there should be no difference between the effects of GMHT cropping and non-
biotech HT cropping, though this has not been compared on a suitable scale. The BRIGHT project 
(Notes, paragraph 14) made some compar isons of GMHT and non-GM HT crops.  
186. A general knowledge of the macro- and micro-fa una in the soil suggests they will be much 
less sensitive to GMHT cropping than will the above-ground flora and fauna. The FSE and some other 
work included macrofauna caught on the soil surface, but no large-scale studies of herbicide tolerance 
have included soil micro-and macro-fauna. (ECOGE N will provide information on soil communities 
at three field sites for Bt maize.) All evidence from small-scale work in field plots and containers 
points to the herbicides glyphosate or glufosinate a mmonium being much less directly toxic to soil 
fauna than other agrochemicals and the GMHT pl ants themselves having no effect on soil organisms 
different from that of non-GM plants. 
Question 8:  What are the different detection methods currently available for testing for the 
presence of material from genetically modified plants?  
(a) Have commercially available detection methods changed since the mid-1990's? Were methods available in the mid-1990's event specific? 
(b) Please outline the steps necessary to va lidate a detection method, including the 
determination of what types of reference materials needed and differences in validation steps for qualitative and quantitative detection methods. 
(c) What are the differences in the intended uses of qualitative and quantitative 
detection methods? What are the diff erences between event specific and non-
event specific detection methods? How does the availability of different types of 
detection methods relate to risk assessment and risk management processes? 
Dr Nutti  
187. Answer 8a: Beginning in the 1990's, commercial protein-based and DNA-based detection 
methods have become available.  Both methods can  be used in a qualitative and a quantitative way.  
Early DNA-based methods have been mainly desi gned as qualitative methods only. More recently, 
there has been a shift towards quantitative PCR me thods. Today, most published methods are based 
on real-time PCR technology that can be operated bot h in a qualitative and a quantitative way.  Some 
DNA-based methods were designed for the identification of a specific event while others were 
designed to identify only a certain vector c onstruct or a common genetic element (e.g., 35S 
promoter).  Today, the development of these three different types PCR methods continues.  The selection of method depends on the intended purpose.  The experience for protein-based methods is 
similar to the experience with DNA-based methods – there are many commercially available protein-
based methods also.  These methods can confirm the presence or absence of specific proteins 
expressed by the different biotech events. These protein-based methods can be applied in both a 
quantitative and qualitative fashion. The protein based methods, while not event-specific, can identify 
uniquely most commercial events. 
188. Answer 8b:  I would like to inform that I am not  an expert in this area, and I will  list bellow 
the information that I could find in order to help the panel, but is important to point out that I will list 
the references and information founde d and not express my personal opinion.  WT/DS291/R/Add.6 
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  Interlaboratory studies : 
189. The International Union of Pure and Applied Chemistry (IUPAC) classify  interlaboratory 
studies into the following three categories: 
 1. Method performance:  Determines the bias and precision of an analytical method. 
 
2. Material performance: Assigns a valu e and an uncertainty (or reliability) to a 
characteristic (usually concentration) of a material.  
 3. Laboratory performance: Permits the ev aluation of each participant against preset 
criteria or criteria estimated from the study itself. 
 
190. Although the procedures regarding statistical data evaluation from these three types of 
interlaboratory studies may be identical, the use and interpretation of the resulting statistical estimates 
will be determined by the primary purpose of the study.   
Validation of methods : 
191. The validation of methods consists of two phases. The first is an in-house validation of all of 
the parameters except reproducibility.  The second is a collaborative trial, the main outcome of which 
is a measure of the repeatability and reproducibility in order to estimate the transferability of methods 
between laboratories.  Usually a small-scale colla borative trial should be performed to test the 
ruggedness of a particular method before the expense of organizing a large-scale trial is incurred. In 
case any improvement of the method or the method description is needed, only limited costs are 
incurred through the pre-trial, while a failure of a full interlaboratory method validation due to an 
ambiguous method description is a very costly failure . Implementation of an already validated method 
in a laboratory needs to include the confirmation that the implemented method performs as well under 
local conditions as it did in the interlaboratory me thod validation. A method must be validated using 
the protocols and reaction conditions under which it will be performed.  
192. The Procedural Manual of the  Codex Alimen tarius Commission, 12th edition, (2001), list the 
main definitions of the parameters for method validation, although the  concepts of a Limit of Detection (LOD), Limit of Quantification (LOQ), and Range of Quantification (ROQ) are not yet 
explicitly defined by Codex Alimentarius , they are listed below in order to  answer this question: 
193. Parameters for method validation:  Accuracy  – The closeness of agreement between the 
reported result and the accepted reference value. A ccuracy describes how close the measured value is 
to the actual value of a known reference sample. 
194. Precision – The closeness of agreement between  independent test results obtained under 
stipulated conditions. Precision describes how well the results agree between re peated analyses of the 
same material. Less precision is reflected by a larger  standard deviation of the combined results than 
the individual results. 
195. Sensitivity – Change in the response divi ded by the corresponding change in the 
concentration of a standard (calibration) curve, i.e ., the slope of the analytical calibration curve.   
196. Specificity – The ability of a method to respond ex clusively to the charact eristic or analyte.  
Specificity describes how often the analyte is  not detected if the analyte is not.... WT/DS291/R/Add.6 
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  197. Ruggedness (Robustness) – The ability of a met hod to resist changes in results when 
subjected to minor changes in environmental and pr ocedural variables, laboratories, personnel, etc. 
198. Applicability – The analytes, matrices, and concen trations for which a method of analysis is 
validated that may be used satisfactorily. 
199. Repeatability – Precision under repeatability conditions. These are conditions in which 
independent test results are obtained with the sa me method on identical test items in the same 
laboratory by the same operator using the same equipment within short intervals of time.   
200. Reproducibility – Precision under reproducibility conditions. These are conditions in which 
test results are obtained with the same method on id entical test items in different laboratories with 
different equipment and operators. 
201. Limit of Detection (LOD) – The lowest amount of  analyte in a sample that can be detected 
with suitable confidence but not necessarily quan tified as an exact value as determined by method 
validation. 
202. Limit of Quantification (LOQ) – The lowest am ount of analyte in a sample that can be 
quantified with suitable accuracy and precision as determined by method validation. 
203. Range of Quantification   (ROQ) – The range within which the amount of analyte in a sample 
can be quantified with suitable accuracy as determined by method validation. 
 I will assume a PCR detection method for outline the necessary steps. According to ILSI 2001, there 
are two primary ways in which PCR is used in th e detection of GM DNA in plants.  These are called 
quantitative PCR, which yields an estimate of the amount of the specific analyte present, and qualitative PCR, which yields a yes/no answer as to the presence of GM material.  
204. The  Sample Preparation is considered the fi rst step and it is necessary to take into account 
the: 
• Sampling the consignment of seed or grain to obtain the bulk sample. 
• Sampling of the bulk sample to obtain the laboratory sample. 
• Subsampling the laboratory sample to obtain the test sample. 
• Sampling the meal that results from grinding the test sample to obtain the analytical sample. 
• Sampling the DNA solution that results from extraction of the meal sample to obtain the test portion. 
205. The  DNA extraction is the second step and DNA qu antification is the third. I could not find 
more details for this topic. I also did not find re ferences for identify the differences in validation steps 
for qualitative and quantitative detection methods but I found that the parameters common to qualitative and quantitative methods are th e specificity and applicability.  
206. Reference Materials:  According to ILSI 2001 , and ISO Guides 30 to 35, reference materials 
play a number of roles in development, validati on and troubleshooting of PCR-based diagnostics, as 
well as in the routine conduct of such assays. In the context of assay validation, positive reference 
materials are used to establish the accuracy, precision, sensitivity, LOD, and the false negative rate in 
quantitative assays.  Negative reference materials are very important in determining the false positive 
rates and specificity. At the ISO guidelines on reference materials, it is defined that they can be of several levels of metrological quality:   WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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                                                       207. A Certified or Standard Reference Material (CRM or SRM) is accompanied by a specific 
certificate. This certificate states that one or more of the property values of the reference material is 
certified by a procedure that establishes the value's tr aceability to an accurate realization of the unit in 
which the property value is expressed; in addition,  the certificate states a level of confidence of  
uncertainty.  Usually these reference materials are issued by National Metrology Institutes. 
208. A Reference Material (RM) is a reference ma terial or substance one or more of whose 
properties are sufficiently homogeneous and well estab lished to be used for the calibration of an 
apparatus, the assessment of a measurement method, or for assigning values to materials. (ISO 
definition).  
209. A Working Standard (WS) is a secondary standard in regular use.  This working standard is 
equivalent to RM if it is quantified/characterized  by comparison with the CRM/SRM.  In order to 
guarantee the quality standards for the reference ma terials, each one should be accompanied by a  
certificate of analysis .  The certificate will describe the characteristics of the material, both as to the 
presence of the target material, and the absence of other possibly interfering materials.  In addition, a 
reference material may even be restricted as to th e method for which it can be used or is validated. 
Usually,  the certificate of analysis for a GM refe rence material will address the  target event or 
sequence; adventitious presence of other events; strength and purity; and genetic background.  The references consulted call the attention for the choice of the reference material, as they can have advantages and disadvantages, according to particular  purposes  and usually there are three references 
materials being used: Grain or seed or seed-deriv ed powders;  GM DNA of plant origin; Plasmid 
DNA or amplicons containing the target sequence.  As  I am not an expert in detection, I asked the 
EMBRAPA technicians in this area and they pointed out  that the key decision is the type of reference 
material to use.  This decision will be influenced by the availability of reference materials and must 
consider the  matrix effects.  In any case, each method should be validated in the laboratory using a 
reference material of the highest metrological standard available (SRM or CRM if possible).  After the validation, the laboratory may  use a referenc e material or working standard that has been 
calibrated back to the CRM/SRM.
42 
210. Answer 8c: Qualitative methods indicate the pres ence or absence of the analytical target; 
quantitative methods give a measure of  the quantity of the analytical target present. For the purpose of 
verifying compliance with thr esholds, both qualitativ e and quantitative DNA and protein based 
methods can be used. It is essential to establis h appropriate sampling plans for both methods. 
Statistical models that build the foundation of th e analysis of grain and seeds are made available 
through ISTA and GIPSA/USDA. 
211. An event-specific DNA-based method determines the presence of a specific trait at a specific 
locus in a plant. A construct specific DNA-based method determines the presence of a gene within a 
 
42 References: 
International Standardization Organization, Geneva, Switzerland:  
ISO Guide 30:1992 "Terms and definitions used in connection with reference materials", 
ISO Guide 31:2000 "Reference materials -- C ontents of certificates and labels", 
ISO Guide 32:1997 "Calibration in analytical chemistry and use of certified reference materials",  
ISO Guide 33:2000 "Uses of certified reference materials",  
ISO Guide 34:2000 "General requir ements for the competence of reference material producers ", 
ISO Guide 35:1989   "Certification of reference materials -- General and statistical principles". 
ILSI (2001) – Ilsi Europe Report Series: Method Development to in Relation to Regulatory 
Requirements for the detection of GMO's in the food chain. Summary report of a joint workshop held in 
December 2000. March 2001 (Prepared by the ILSI Euro pe Novel Food Task Force in collaboration with the 
European Commission's Joint Research Centre (JRC) and ILSI International Food Biotechnology Committee) WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  plant, independent of its specific integration lo cus; a screening method determines the presence of 
certain genetic elements, such as a promoter or a terminator. Protein based methods confirm the 
absence or presence of specific expressed traits such as herbicide tolerance or insect protection 
proteins. 
212. Detection methods as applied to food or feed labeling do not have a direct role in risk 
assessment or risk management.  However, while similar methods are used to establish the level of proteins in genetically modified products, and these levels are relevant to dietary intake and exposure 
assessments that form the basis of risk assessment, the common understanding of "detection methods" 
is that they are used to describe the presence or absence of GMO grain (or seed) in the context of 
conventional grain (or seed).  Thus, there are two ki nds of methods: methods that measure the analyte 
in the grain for the purposes of characterization a nd risk assessment, and methods that detect the 
presence or absence of the GMO (or level of the GMO) in  seed, in grain or in a finished food or feed.  
The manuscript referred to above describes the use of detection methods for this second purpose.
43   
Question 9: In what ways does molecular charac terization inform the risk assessment for 
any particular biotech product? Can a risk assessment be carried out in the absence of a 
comprehensive molecular characterizati on of each transformation event? 
Dr Nutti  
213. Answer 9: According to the Codex Alimentarius Guidelines for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003, Paragraph 18), the 
food safety assessment follows a stepwise process of addressing relevant factors. Molecular 
characterization informs the risk assessment the st eps of the food safety assessment related to the 
description of the recombinant-DNA plant, description of the genetic modification and 
characterization of the genetic modification. Ho wever, all the safety assessment steps must be 
fulfilled. My understanding is that the knowledg e achieved with a comprehensive molecular 
characterization of a transformation event is fundamental for the food safety assessment of a biotech product and, consequently, for its risk assessment. 
214. The molecular characterization of a particular biotech product can be used to determine the 
presence and absence of certain DNA-sequences.  It can be further used to determine the integrity of 
the inserted DNA, whether the sequence that was in tended to be introduced was indeed introduced 
and whether it was introduced in a way that produces the expected protein products. Specific types of 
molecular characterization could also be used to  assess the amount of a certain DNA-sequence.   
215. Sometimes, the term molecular characterization includes the biochemical characterization of 
expressed proteins, and will include the description of the mode of action of a protein.  Thus, 
conclusions about the safety of an inserted DNA sequence and its expression product is dependent upon: potential effects resulting from the assessment of the function of a gene, the mode of action a of 
any encoded proteins; the relatedness of the inserted pr otein to proteins that have a history of safe use 
or are related to protein toxins or allergens. This  evaluation needs to incorporate the biochemistry of 
                                                      
43 References:  
ILSI (2001) – Ilsi Europe Report Series: Method Development to in Relation to Regulatory 
Requirements for the detection of GMO's in the food chain. Summary report of a joint workshop held 
in December 2000. March 2001 (Prepared by the ILSI Europe Novel Food Task  Force in collaboration 
with the European Commission's Joint Research Centre (JRC) and ILSI International Food 
Biotechnology Committee)  
  WT/DS291/R/Add.6 
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  the organism the gene was introduced into, the organisms' intentional use, the conditions under which 
the organism is cultivated, its interactions with the environment, and related factors. 
Dr. Andow  
216. A risk assessment cannot be carried out in the absence of a comp rehensive molecular 
characterization of each transformation event.  A risk assessment could not address the risks specific 
to the transgene of interest without this informati on.  Without the information, there would be no clear 
basis for knowing when all reasonable scientific risk s have been assessed and there would often be an 
uncertain basis for determining if a specific risk w as scientifically justifiable or unjustifiable.   
217. Molecular characterization addresses three distin ct issues:  (1) specification of expected 
expression of the transgene in the plant; (2) charact erization of expression of the transgene in the 
plant; (3) genetic stability of the transgene under transmission to offspring. 
218. Specification of the expected expression of the transgene in the plant is necessary to 
characterize expression and to begin to clarify scientifi cally what can be considered an expected effect 
and an unanticipated effect.  Since about the year 2000, it has been technically routine and reliable to 
determine the number of transgene loci, the copy nu mber at each locus, and of DNA sequence each 
transgene locus.  For some crops, most notably ma ize, it was also possible to sequence out from the 
transgene through adjacent DNA until distinct plan t DNA sequences could be identified (these are the 
so-called flanking regions).  In 200 1 this was not possible for some cr ops, such as cotton.  Many other 
molecular methods are under development, including proteomics and others, but these are not yet 
ready for use in risk assessment now.  It is likely that some of these tools will become available in the 
future.44  
219. Characterization of expression of the transgene in  the plant is necessary to specify all gene 
products from the transgene locus or loci and to determine their patterns of expression (concentrations of gene products) in the plant, both as the plan t develops over time and as it generates new tissues and 
plant parts.  All gene products must be identified so  that their effects can be assessed.  If they are not 
all identified, unanticipated effects could result fro m the unidentified products.  It is important to 
characterize patterns of expression because transgenes  are typically expressed differently in different 
plant tissues and expression in a plant tissue typically changes over time.  In several cases, measured differences among tissues and changes over time ha ve proven significant for risk assessment. 
220. Genetic stability of the transgene under transmissi on to offspring is needed to demonstrate the 
transgene behaves similarly to ot her plant genes through development and reproduction.  If it was not 
stably inherited, most likely it would be silenced or  excised or otherwise inactivated.  In some such 
cases, this could lead to unanticipated effects.   
221. There is a paper that outlines the rationale fo r molecular characterization in detail for a 
particular case.45 
                                                      
44 Nap, J.-P., A. Atanassov and W. J. Stiekema (eds).  2004.  Genomics for Biosafety in Plant 
Biotechnology. IOS Press: Amsterdam, 247 + viii pp. 
45 Andow, D. A., D.A. Somers, N. Amugune, F. J. L. Aragão, K. Ghosh, S. Gudu, E. Magiri, W. J. 
Moar, S. Njihia and E. Osir.  2004.  Transgene locus structure and expression of Bt maize, pp. 83-116.  In A. 
Hilbeck and D.A. Andow (eds), Environmental Risk Assessment of Transgenic Organisms: A Case Study of Bt 
Maize in Kenya .  CABI: Wallingford, UK. WT/DS291/R/Add.6 
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  Dr. Healy  
222. General Approach to Assessing Safety :  It is well accepted that assessment of whole foods, 
such as foods from genetically modified organism s (GMOs; GM foods), involves the use of the 
'comparative approach', whereby GM foods are comp ared to their counterpart foods produced using 
conventional techniques and which have been safely consumed over significant periods of time.  The 
objective of such a comparison is to identify any di fferences with the conventionally produced food.  
Any identified differences are then examined for their biological impact in terms of health and safety. 
223. This approach to the assessment of the safety of food products has been advocated for over a 
decade (OECD, 1993,1996; WHO, 1991; 1996) and reconfirmed several times during that period.  
Most notably, a relatively recent expert consu ltation convened by WHO/FAO concluded that 'a 
comparative approach……is consider ed the most appropriate strate gy for the safety and nutritional 
assessment of genetically modified foods' (WHO, 2000) .  This approach is used in place of the 
traditional approach of assessing the safety of discr ete chemicals added to, or present in, food (eg food 
additives, contaminants) that are generally subjected to a range of toxicological evaluations in animal 
studies in a dose dependent manner (WHO, 1987).  The toxicological approach is not appropriate for 
whole foods because of the complex mixture of ch emicals present in a whole food, some of which 
will be present at very low levels, and the difficu lty of conducting meaningful dose response studies 
in animals while providing a nutritionally balanced diet. 
224. The comparative approach to ex amining the safety of a GM food is generally considered to 
encompass three major elements: molecular charact erisation of the inserted gene (transgene); 
biochemical, structural and functional properties of the protein product from the inserted gene; and 
analysis of the composition of the food.  This approach taking into account knowledge about the 
organism from which the transgene is sourced as we ll as the recipient organism.  Application of the 
comparative approach has been examined in de tail for food derived from GM plants (WHO, 2000; 
WHO, 2001a), GM micro-organisms (WHO, 2001b) and GM animals (WHO, 2003).   
225. The totality of  information available from these types of studies should be considered in 
coming to a view about the safety of the food; information from each element contributes to the 
assessment of safety.  Analyses of the information about these three aspects of the GM food provides a structured mechanism to identify both the intended changes to the food as well as any that may be an unintended consequence of the genetic manipul ation.  Some unintende d consequences may be 
predicted while others are unexpected. 
226. The comparative approach involving characterisation at the DNA, protein and compositional 
levels has been generally accepted and applied by  many countries around the world, some for more 
than a decade.  These countries include Austra lia and New Zealand (ANZFA, 2001), Belgium (Van 
Haver et al, 2003 ), Canada (Health Canada, 1994), European Union Member States (SCP, 1999; 
EFSA, 2004), Japan (Japanese MHLW 2001), United Kingdom (UK FSA, 2003) and the United States (USA FDA, 1992, 1997, 2001).   Approaches by other countries are summarised in OECD, 2000 and Kuiper et al, 2001.  A significant number of foods from GMOs have now been approved using this assessment approach (eg Japan
46, Australia/New Zealand47, Canada48, USA49 and 
Europe50).  International consensus on the appropriaten ess and utility of this approach resulted in the 
                                                      
46 http://www.mhlw.go.jp/english/topics/qa/dna/index.html. 
47 http://www.foodstandards.gov.au/whatsinfood/gmfoods. 
48 http://www.hc-sc.gc.ca/food. 
49 http://www.cfsan.fda. gov/~lrd/biocon.html. 
50 http://europa.eu.int/comm/food/ food/biotechnology/authorisation/258-97-ec_ authorised_en.pdf.  WT/DS291/R/Add.6 
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  development of international guidance on the asse ssment procedures by the body responsible for 
developing international food standards, the C odex Alimentarius Commission (CAC, 2003a, b, c, d). 
Role of Molecular Characterisation in Risk Assessments 
NOTE: QUESTION 9 REFERS TO THE ROLE OF MOLECULAR CHARACTERISATION IN A 
'RISK' ASSESSMENT.  HOWEVER, I HAVE AN SWERED THE QUESTION IN THE CONTEXT 
OF A 'SAFETY' ASSESSMENT, WHICH IN RELATION TO EXAMINING THE HEALTH AND 
SAFETY IMPACT OF FOOD, HAS A DEFINED MEANING (CAC 2003A) AND MAY BE PART 
OF A SUBSEQUENT RISK ASSESSMENT IF POTENTIAL HAZARDS ARE IDENTIFIED 
DURING THE SAFETY ASSESSMENT.  
227. The molecular characterisation is considered to be a very important part of the safety 
assessment of a biotech product.  It provides in formation about the number of copies of the 
transgene(s) that have been inserted, presence of  any multiple copies at the same or dispersed 
insertion site(s) and the structural organisation of the inserted transgene(s).  The molecular 
characterisation also includes an analysis of th e stability of  the inserted DNA.  Together this 
information provides verification that the intended genetic modification has occurred and provides 
some indication as to the likelihood of any un intended changes.  However, the molecular 
characterisation is not the only mechanism for id entifying unintended effects and the information 
from such studies should be considered in conjuncti on with the information from the other elements 
of the safety assessment. 
228. While a safety assessment could be conducted in the absence of a comprehensive molecular 
characterisation, current international good practi ce includes the molecular ch aracterisation (CAC b, 
d).  However, the issue does arise as to how comprehensive the molecular characterisation should be in order to fulfil the requirements of an appropriate safety assessment.  In large part, the answer to this 
question depends on the type and quality of informati on available for the three elements of the safety 
assessment, the information revealed from these st udies and the state of the scientific knowledge 
about the gene(s) to be transferred, the donor organism and the recipient organism. 
229. In recent years, there have been significant developments in the technologies to analyse the 
molecular biological and biochemical characteris tics of GMOs and their products (eg DNA sequence 
analysis, reverse transciptase polymerase chain reac tion, bioinformatics; micro array technologies, 
proteomics and metabolomics).  In some cases, these technologies can already significantly assist the 
safety assessment.  A recent example is the ready generation of DNA sequence data.  It should be noted that the guidelines for conducting safety assessments of GM foods that were recently adopted by the Codex Alimentarius Commission (CAC 2003 b,  d) require information sufficient to identify 
any new substances that may be included in food.  DNA sequence information on the junction regions 
of the transgene and for the transgene itself is one mechanism to obtain this information.   
230. It is now regarded as good practice to undertake DNA sequence analysis as part of a safety 
assessment, for several reasons.  First, some of  the gene constructs and the transformation 
technologies available today result in more complex segments of DNA and in rearrangements of the inserted DNA.  One of the most effective methods currently available for assessing the integrity and impact of the inserted DNA is sequencing.  Second, sequence information can now be much more readily generated than was possible using the laborious procedures available a decade ago. 
231. Although this type information has not genera lly been required in the past, a number of 
countries have now included requirements for its pr ovision in the future.  However, countries have WT/DS291/R/Add.6 
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  generally not required such information for GMOs a nd their food products that have previously been 
approved for entry to the marketplace.   
232. Some of the technologies being developed are currently not appropriate for use in safety 
assessments as they do not yet provide any further assu rance of safety or the results cannot be fully 
interpreted (eg NAS, 2004).  However, some of the profiling methods, such as metabolomics, may 
eventually prove very useful.  At some point in  the future, the development of these technologies and 
associated understanding about the impact of sma ll variations in gene expression levels and/or 
metabolites may be adequate, minimising th e need for molecular characterisation. 
233. It must also be acknowledged that the commerc ially produced GMOs gene rated to date have 
utilised well defined crops as recipients of the gene tic modification and well defined genetic elements 
in the transgenes.  Generally, the genetic elements have been extensively studied at both the DNA and 
protein levels. Consequently there has been a high level of confidence in the assessments carried out 
to date.  However, there have been ongoing develo pments in the molecular biological technologies 
that are being applied in the development of GM  crops (eg different transformation technologies; 
insertion of multiple and different genes; differe nt donor and recipient organisms) and these are 
raising new and more complex questions about the saf ety of the products of such crops in the food 
supply. 
234. Conclusion :  Currently the molecular characterisation is an important element of the safety 
assessment, providing verification that the intended genetic modification has occurred and 
information about unintended effects.  The extent of  molecular characterisation in any particular case 
should be addressed in the context of th e available scientific information.  
235. Approach to Addressing Specific Questions About Molecular Characterisation :  
Questions relating to requests for additional information for safety assessment purposes have been 
considered in the context of the general approach to assessing the safety GMOs and their food 
products.  In particular, requests for further molecular characterisation have been considered 
according to the principles and approaches outlined above. 
Dr. Squire  
236. The Guideline for the conduct of food safet y assessment of foods derived from recombinant-
DNA plants indicate full characterisation of the gene tic change should be provided. Such information 
may be essential for assessing some aspects of th e product but is not always necessary when 
considering spread or persistence of the biotech product or its effect on the ecosystem.  
237. Spread and persistence. In many of the studies in Europe (ongoing and not yet published), the 
purposes of the study can be achieved by detection based on an outward or phenotypic trait (i.e. whether a plant dies if sprayed with a specific herbicid e), a protein test (e.g. an antibody based test for 
the protein produced by the genes conferring tolera nce to glyphosate or glufosinate ammonium) or a 
DNA test for the gene (e.g. the bar gene). None of  these tests is absolutely accurate since they are 
affected by the condition of the plant tissue. If samp ling of plant material is done in real agricultural 
fields, it is impossible to ensure the plant tissu e is in the right condition – often it is not. 
Consequently, false-positives and false-negatives occur. Moreover, if the GM trait is thought to be at low frequency, e.g. 0.5% or lower, and the individuals possessing it are unevenly distributed or clumped in the field, then very large numbers of individuals have to be sampled to estimate presence 
or % frequency with a high degree of certainty.    WT/DS291/R/Add.6 
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  238. Ecological impact. For some aspects of comparing GM and non-GM plants, detailed 
knowledge of the molecular construc t is not necessary. For instance, if comparing the ecological 
effects of GMHT or Bt plants, the studies coul d be done equally well wi thout detailed molecular 
knowledge of the construct.  
239. More information would be necessary if r esearch was following the volunteers or pollen-
vectored genes originating from the GM crop: at least, knowledge of the genetic factors determining 
the proportions of male sterility and male fertility  would be important, but even then the detailed 
molecular knowledge of the construct would not be  essential. However, if many GM varieties had 
been grown in an agricultural area, and if it were important to ascertain the origin of an individual plant or population, then more detailed mol ecular characterisation would be required.  
240. More generally it can be argued, given the scientific  and public interest in GM issues, that it is 
reasonable for an assessing body to request full ch aracterisation (according to standards in the 
Guideline for the conduct…) of a GM construct (a) to enable its officers to confirm whether 
impurities existed in the original seed if they we re found or suspected (e.g. the presence in the 
breeding line of GM traits such as antibiotic resistance) and (b) to trace the persistence or spread of 
the GM trait if this was necessary in later years.  
241. While much of the text above under Responses 9 is generally appreciated by workers in the 
field, many of the scientific findings pertaining to th e spread and persistence of GM traits in Europe 
are not yet in the public domain (Notes, paragraph 14). 
ISSUE 1  
 
Background:   The following questions have the objective of assisting the Panel to determine whether 
the EC regulatory approval process for the specific  biotech products at issue in this dispute 
proceeded without unjustified delays on the part of the relevant EC regulatory bodies. The questions 
are aimed at determining for each product application (whether pending or withdrawn): 
 
(a) the scientific or technical grounds for the comments and/or objections raised by EC 
member States following the initial assessments of  the Competent Authority (CA) and of the 
relevant EC scientific body, in light of the sci entific evidence and evaluations available at the 
time; 
 
(b) the scientific or technical grounds for the requests for additional information from 
the notifier during or following the initial a ssessments of the CA and of the relevant EC 
scientific body, in light of the scientific eviden ce and evaluations available at the time; and 
 
(c) the justification on scientific or technica l grounds for the time taken to evaluate the 
additional information provided. 
 
Questions:  
 
Bayer oilseed rape (Falcon GS40/90)  
C/DE/96/05 (EC chronology 62) 
 
Question 10:  Given the information before the Pa nel, including the notification by AgrEvo (EC-
62/At.1-30) and the EC Scientific Committee for Plant (SCP)'s opinion (EC-62/At.74), was the information to assess the long-term effect of th e newly expressed protein on the biogeochemical WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-58 
  
  cycle and the food chain requested by the Ita lian CA (EC-62/At.95) necessary to ensure that 
conclusions of the safety assessment were valid? 
Dr. Nutti  
242. Based on the information provided by the appli cant and the analysis carried out by the EC 
Scientific Committee for Plant (SCP) and following  the Codex Guidelines, my understanding is that 
the request by the Italian CA (EC-62/At.95) was not necessary to ensure that conclusions for the 
safety assessment of the newly expressed protein in the food chain were valid. As pointed out by the 
EC SCP, the new protein has a very low potential for being allergenic or toxic and also is degraded 
within the gastric fluids. In my opinion, the conc lusion of the EC SCP that the protein was safe for 
consumption in the food chain is correct and w as based on sound scientific evidence, which was 
presented by the applicant.  
Dr. Andow  
243. The request by the Italian CA (EC-62/At.95, 14 March 2000) is repeated below. 
Referring to the conclusion of the last meeting of the Regulatory Committee under 
Directive 90/220/EEC, Italy would be very pleased to receive from the notifier more information concerning the assessment of the effect of the genic product on the 
biogeochemical cycles and on food chain and on the apreading of the gene due to the possibility of crossing between the PGM and wild species. 
244. The original notification by AgrEvo (EC-62/At.1-30, 1 April 1996) contains no studies on the 
safety of Falcon GS 40/90 to other organisms and no studies on outcrossing rates with wild species.  
Instead, the notifier argues that Falcon GS 40/90 is  in no way different from non-transgenic cultivars 
expect for the ppt gene.  They conclude that ther e is no reason to believe that Falcon GS 40/90 has 
any adverse effects on the environment. 
245. In my reading of the original notification,  AgrEvo's claim rests entirely on the SCI report 
"Glufosinate tolerant transgenic Winter Oil Seed Rape – Field observations of the variety Falcon GS 
40/90 pHoe6/Ac in comparison to Falcon non transgenic and conventional fa rmers rape," which is 
code number Hoe 039866 00 SL 01 A 201 (EC-62/At.30_SCI, 1 April 1996), and on the report "Supplementary ecological monitoring of a transgenic , Basta-resistant winter rapeseed crop cultivated 
at Friemar (Thuringia, Federal Republic of Germ any) during the season 1994/95" (EC-62/At.8).  I 
agree with the assessment of the lead CA that EC-62/ At.8 is difficult to interpret.  Without going into 
the details, the data are not scientifically convin cing that the environmental effects of Falcon GS 
40/90 are in no way different from non-transgenic cultivars. 
246. The lead CA requested improvements to EC-62/At.8 on 14 May 1996 (EC-62/At.33) and 
received an improved version from the notifier on 12  July 1996 (EC-62/At.37_SCI).  This includes a 
revision of EC-62/At.8.  The notifier admits that the small plot size in EC-62/At.8 precludes statistical 
analysis, so I conclude that the data are of li mited scientific value for evaluating environmental 
effects.   
247. The full application to the community was not incl uded in documents before the Panel, so it is 
not possible to determine conclusive ly the basis for the SCP assessment. 
248. Between the time of submission of the full appli cation to the community and the time of the 
SCP Opinion, there were several requests for information to the notifier from various countries and  WT/DS291/R/Add.6 
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                                                       the SCP.  The replies from the notifier are in EC- 62/At.45, EC-62/At.52, EC-62/At.54, EC-62/At.68 
and EC-62/At.71.  Information in EC-62/At.52 and EC-62/At.71 are relevant to the question at hand. 
249. In EC-62/At.52, 28 January 1997, the notifier clarified as follows: 
42.  Survival, multiplication, and dissemination of the GMO(s) in the 
environment : 
The comparison study mentioned in this section has only taken place in a growth 
chamber which is big enough to handle ev en maize plants.  Field observations are 
discussed in document A 56991. 
Five plants each from the recipient and from the transformant have been analysed in 
the growth chamber. 
250. In EC-62/At.71, 5 June 1998, the notifier provided extensive information related to 
environmental impact that was not available previo usly.  This addressed dispersal of oilseed rape 
pollen, the potential invasiveness51 of Falcon GS 40/90 oilseed rape, and a number of aspects related 
to fitness, weediness and outcrossing (data and sources not provided). 
251. The SCP concluded that there is no evidence to indicate that Falcon GS 40/90 is likely to 
cause adverse effect on human health and on th e environment (EC-62/At.74, 14 July 1998).  
However, they also indicate that "Few studies have  been conducted on the safety of modified oilseed 
rape to other organisms."  No studies were conducte d on biogeochemical cycling or on the food chain. 
252. It must be stated clearly at this point that th e lack of evidence does not imply that there is a 
lack of an effect.  Either the SCP did not base their conclusion about non-target effects on sound scientific reasoning or the reasoning they used is no t apparent from their Opinion (EC-62/At.74).  In 
either event, their conclusion does not follow from the data provided by the notifier.   
253. The SCP did address the possibility of the spr eading of the gene due to crossing between 
Falcon GS 40/90 and wild species.  The SCP indicated that the likelihood of crossing to wild species 
was small, especially when compared to the likelihood of crossing with another oilseed rape cultivar.  
They suggested that appropriate risk management measures would be likely to avoid these risks. 
254. The conclusions by the SCP related to outcr ossing and invasiveness are based on the sound 
interpretation of the data present at the time.  Howeve r, there is likely to be several approaches to risk 
management, and these are not specified.  
255. The Italian CA (EC-62/At.95) requested inform ation to assess the long-term effect of the 
newly expressed protein on the biogeochemical cy cle and the food chain.  While a request for 
additional/ clearer assessment of the possible effect s on environment can be readily justified on the 
basis of the preceding analysis, such a request must it self be clear and specific.  For example, it is not 
clear that all of the environmental hazards have  been identified let alone assessed.  A request for 
additional/ clearer assessment of the possible effects on the environment would not be clear or 
specific enough to allow a notifier to know how to respond, and hence although information on the 
environmental impacts is necessary to ensure that conclusions of the safety assessment were valid, a 
general request for such an assessment would not be an appropriate way to request such information.  
In a similar way the request by the Italian CA is not clear or specific enough to be considered 
 
51 Crawley et al. Nature 363: 620-622. WT/DS291/R/Add.6 
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  necessary.  There are hundreds of possible processes in biogeochemical cycles that could be 
investigated, and thousands of possi ble ways to evaluate food chains.  Unless the Italian CA can point 
to prior regulatory precedents wh ere these terms are clarified, the phrasing of the request is not 
scientifically justified.  Alternatively, had the It alian CA specified certain biogeochemical cycles and 
food chains to assess, then it would be possible bo th for the notifier to assess them and for me to 
determine their necessity to ensure that conclusions of the safety assessment were valid. 
256. The Italian CA request came on 14 March 2000 .  On 10 November 1999 Aventis submitted 
and updated notification, which was circulated  to the CAs on 13 December 1999.  The AFFSA 
Opinion was issued 5 January 2000 and Aventis provided additional information on 28 February 
2000.  The time between the receipt of materials un til the Italian CA response can be calculated as 
either 15 or 125 days.  Of the 125 days, 33 were used to process the file administratively, and Italy had the materials for 92 days.  The shorter time is a very rapid response time.  The longer time is probably too long, but mainly because 33 da ys seems excessive for processing the file 
administratively. 
Question 11:  Given the information before the Pa nel, including the notification by AgrEvo and 
the conclusions of the EC SCP, was the info rmation regarding the post-event monitoring 
protocol to assess the likelihood of spreading re quested by the lead CA necessary to ensure that 
conclusions of the safety assessment were val id (EC-62/At.100)? If so, what other risk 
management options are available to mitigate this risk?  
Dr. Nutti  
257. Three questions presented in EC-62/At.100 are on environmental issues. I can only refer to 
item 7.3 (oilseed rape animal feeding study), where a doubt was raised about which event was used in 
the male broiler chicken studies. It is mentioned in  EC-62/At.103 that copies of both studies were 
submitted by the notifier in order to answer this point. I could not find these studies in the 
attachments, but examining the information provided by the applicant to EC and the answers given in 
EC 62 (Attachments 003, 005, 006, 007, 010, 011, 012, 015, 017, 018, 019, 021, 022, 023, 024, 025, 
026, 027, 028, 049, 050, 051, 053, 057, 060, 063, 065, 071, 073, 074, 075, 081, 082, 085, 091, 093 and 0103) and the analysis carried out by the EC Scientific Committee for Plant (SCP) (Exhibit US-42), where it is relevant to note: 
258. Item 7 (Overall Assessment): "there is no evidence to indicate that the placing on the market 
of line transformant Falcon GS 40/90 oilseed rape, with the purpose to be used as any other oilseed 
rape is likely to cause adverse effects on human health and on the environment".  
259. Item 6.2.2: "in food of animal origin from liv estock animals fed with feedingstuffs after the 
application of glufosinate-ammonium to tolerant  rape, no residues are expected above the limit of 
determination".  
260. My understanding is that there is no significant risk to humans or livestock with the ingestion 
of the gene product. All the food safety aspects indi cated in the Codex Alimentarius Guidelines have 
been accomplished. It is important to point out that the nutritional composition of the entire seed, meal and oil from the genetically modified rape has been analysed. Information on the contents of oil, fibre, ash, protein, fatty acid composition, glucosinolate, sterols and tocopherols showed no differences that could be attributed to the genetic  modification. The Scientific Committee for Plants 
appointed within the EC Commission has, in its opinion on rape, stated that no significant changes in nutritional value have been identified.   WT/DS291/R/Add.6 
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  261. I cannot express any opinion on the post-event monitoring protocol since this is an 
environmental issue. According to the follow- up programme, monitoring will be carried out on 
herbicide use, biodiversity and spread of the gen es introduced via waste plants and wild relatives. 
Dr. Andow  
262. The information requested by the lead CA rega rding the post-event monitoring protocol to 
assess the likelihood of spreading is in EC-62/At .100, 25 July 2001, a nd reproduced below. 
Ad_Document_3 ("Draft Post-Marketing Monitoring Plan for InVigor ®, SeedLink ® 
and LibertyLink®  Oilseed Rape"): 
III.2.  "Existing networks of experti se to carry out General Surveillance": 
On principle, we think that a more deta iled description of the tasks and the kind of 
data that will be collected by the different  networks would further acceptance of the 
monitoring plan by the other Member States.   We expect that relevant information 
will be supplied by Aventis after the diffe rent networks have elaborated their 
programs for the general surveillance. 
III.2.2.  "Plant protection networks": 
In Germany, the "Bundessortenamt" is th e competent authority for plant variety 
registrations (as mentioned under III.2.1.),  but its focus is not on evaluating the 
impact of agricultural practices on the environment, specifically on water, soil, 
wildlife and flora.  Since several federal and regional ("Länder") authorities are responsible for these questions in Germany, it would be difficult to give a complete list.  We suggest either to omit reference to a particular institution in Germany or, alternatively, to mention – as the main  federal and regional institutions – the 
"Biologische Bundesanstalt für Land- und Forstwirtschaft", the "Umweltbundesamt" and the "Pflanzenschutzämter". 
263. The first mention of a monitoring protocol is in the SCP Opinion (EC-62/At.74, 14 July 
1998).    
2.  The SCP is also of the opinion that the potential transfer of the herbicide resistance 
gene to wild Brassica relatives is a new issue in Europe in view of the limited scale of release to date.  The SCP has examined the available evidence from monitoring and 
research programmes to date.  After evaluating all the information available to the SCP, it was concluded that herbicide tolera nt volunteers that may appear would be 
canola plants and not wild Brassica relativ es.  Such herbicide-tolerant volunteers 
could be controlled in subsequent crops by conventional agricultural methods other 
than by the use of glufosinate-amm onium.  The SCP recommends that the 
introduction of herbicide tolerant crops should be accompanied by: 
i)  an agreed code of practice for field ma nagement of the particular modified crop 
involving the active participation of the notif ier to promote best practice by farmers. 
ii)  a research programme with an agreed design and implementation plan to detect the occurrence and the establishment of herbicide tolerant volunteers and weeds 
under field conditions in the EU. WT/DS291/R/Add.6 
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                                                       264. The SCP is recommending a "code of practice" in order to ensure that herbicide-tolerant 
volunteers are eliminated.  In other words, the purpose of the risk management measure is to eliminate 
volunteers as they occur.  In addition, it is re commending research design and implement monitoring 
to detect herbicide-tolerant volunteers and herbicide-tolerant weeds in the EU.   
265. The notifier indicates they are developing a monitoring plan in EC-62/At.75, 22 June 1998, 
even before the SCP is published), with some deta ils in Annex 3.  Annex 3 is not a part of the 
materials before the Panel. 
4.  that PGS and AgrEvo contribute to and collaborate with different programmes 
monitoring the occurrence and establishment  of herbicide tolerant volunteers and 
weeds under field conditions.  In annex we present examples of collaborations in the 
UK, France and Germany.  PGS and AgrEvo will keep the Scientific Committee on 
Plants as well as the competent au thorities informed of the results. 
266. The notifier provided a monitoring plan (EC62/At.78, 25 January 1999) entitled "A 
Structured Stewardship and Monitoring Programme for Agronomic Impact of Growing LibertyLink™ 
and SeedLink™ Oilseed Rape in Europe – A mon itoring and quality assurance strategy."  The main 
objective of this plan is to increase understanding of  the appropriate management of these products by 
their users and to improve public awareness and acceptance.52 The second objective is to promote 
practices, which ensure the quality and stability of the crops, in both the farmers' and AgrEvo's own 
interest.53   
267. In the monitoring plan is a section entitled "2 .3.2 Which Guidance?" in which the notifier 
states that they will provide farmers with guidan ce on volunteer management: post-harvest treatment 
of the area.  However, there are no details on the gui dance that will be provided.  Moreover, there is 
no concrete discussion on how a monitoring plan will be implemented (see my answer to question 24a 
for criteria on judging the completeness of a monitoring plan). 
268. This monitoring plan (EC62/At.78, 25 January 1999) does not meet the specifications 
suggested by the SCP. 
269. In EC-62/At.81-82, 8 July 1999, the notifier rep eats information in EC-62/At.71, 5 June 1998. 
270. In EC-62/At.83, 3 August 1999, the notifier reiterates the content of EC-62/At.78, 25 January 
1999. 
271. In EC-62/At.90_SCI, 10 November 1999, the notifier modifies the proposed monitoring plan 
from that in EC62/At.78, 25 January 1999.  The main objective is still to increase understanding of 
the appropriate management of these products by their users and to improve public awareness and 
acceptance.  There is no secondary objective.  [xxx] 
272. The lead CA requested (III.2 in EC-62/At.100, 25 July 2001) more deta iled description of the 
tasks and the kind of data that will be collected  by the different networks.  As the monitoring 
objective of the notifier does not fully correspond wi th the monitoring recommendations of the SCP, 
or monitoring objectives of what will become Annex VII of Directive 2001/18/EC, and there are few details in any of the proposed monitoring plans submitted by the notifier, and the submitted 
monitoring plans do not address the main manage ment measure recommended by the SCP (how 
 
52 EC-62/At.78, p. 9 of pdf file. 
53 EC-62/At.78, p. 9 of pdf file.  WT/DS291/R/Add.6 
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  conventional practices will eliminate volunteers), th is request for additional information is necessary 
to ensure that conclusions of the safety assessment were valid.  
273. The lead CA also requested (III.2.2 in EC-62/At.100, 25 July 2001) a modification to the list 
of proposed plant protection networks  that will participate in monitoring.  This seems like a useful and 
important suggestion to the notifier, and should be c onsidered necessary to ensure that conclusions of 
the safety assessment were valid. 
274. There are many other possible risk management  options to the monitoring systems proposed 
by the notifier.  The most evident is to follow up rigorously on the SCPs original suggestion that 
conventional practices may be sufficient to eliminat e volunteers.  This would require the notifier to 
consider all the possible practices that may follow  an oilseed rape crop and determine which aspects 
of these are responsible for elimination of volunteers.  I would suggest that the competitiveness of the 
subsequent crop, the phenology of crop management  activities (disturbance regime), and management 
of field margins (tillage or herbicide application) may be critical factors that would be sufficient to 
eliminate nearly all volunteers.  Monitoring would shift from looking for glufosinate-tolerant 
volunteers and weeds to monitoring the cropping prac tices of farmers.  Monitoring for glufosinate-
tolerant volunteers and weeds could then be restricted to those farmers or regions where management of the subsequent crop was inappropriate for eliminating volunteers. 
275. The lead Ca requested the information on 25 July 2001.  The notifier provided the reviewed 
proposal on 10 November 1999.  This is a 1 y ear 8 month interval, and is excessively long. 
Dr. Snow  
276. In summary, asking for information about the post-event monitoring protocol appears to be 
justified for two reasons.  First, when the EC SC P rendered its opinion in July 1998, questions were 
raised about how quickly transgenic resistance to glufosinate would spread to volunteer oilseed rape plants and to weedy Brassica rapa.  The EC SCP stated that these questions could be addressed by 
post-release monitoring.  Second, information about  monitoring is now required under EC Directive 
2001/18, which went into effect in March 2001.  Discussions about whether to require monitoring 
protocols were probably taking place while the pr evious Directive was in effect as well.   
277. With regard risk management options, the spr ead of volunteer oilseed rape or wild Brassica 
species that acquire resi stance to glufosinate can be managed by other methods of weed control, 
including applications of other herbicides.  However, if glyphosate-tolerant oilseed rape is introduced 
in the future, problems with herb icide-resistant volunteers could be compounded.  This concern is 
mentioned specifically in the EC SCP (EC-062-At. 074). 
278. I noticed two shortcomings in the notifica tion for Falcon GS40/90 by AgrEvo (EC-062-At. 
003) and the July 1998 conclusions of the EC Sc ientific Committee on Plants (SCP; EC-062-At. 074): 
(a) The documents show that both AgrEvo and the EC SCP concluded that transgenes from oilseed rape are unlikely to spread to weedy Brassica rapa and multiply, despite 
the fact that several early studies showed  that persistence of the transgenes is 
expected (Jeorgensen and Andersen 1994, Mikkelsen et al. 1996, Snow et al. 1998).  
The SCP stated ". . . there may be a very low level of natural crossing with related 
species particularly Brassica rapa and Brassica juncea under field conditions. . . The risk assessment assumes that transfer will occu r at a very low level."  This could be 
correct, depending on local conditions.  Ho wever, the EC SCP then stated: "After 
evaluating all the information available to the SCP, it was concluded that herbicide WT/DS291/R/Add.6 
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  tolerant volunteers that may appear would be canola plants and not wild Brassica 
relatives."  The basis for this conclusion is not clear (also, it doesn't make sense to 
refer to wild relatives as a type of volunteer). 
(b) AgrEvo and the EC SCP did not specifically address the issue of how the widespread 
adoption of glufosinate-tolerant canola would affect the efficiency of weed control, 
which has implications for biodiversity in farmland habitats (see above).  This question had not been evaluated at the time and is still under investigation. 
Dr. Squire  
279. If long term events or emergent properties are envisaged as a result of introducing a GM plant 
and practice (and this seems to be the case for oilseed rape in Europe), then it is legitimate to expect a 
rigorous post-event monitoring protocol to be integral to a pre-release risk assessment. Risk management options for this GMHT product are si milar to the generic ones included in Responses 
6d-e. When they are applied, the practices appear  to work in keeping weedy oilseed rape to 
manageable levels, but the gene ral level and type of management have not prevented it from 
becoming established throughout Europe as a weed. 
Question 12:  Given the information before the Pa nel, including the notification by AgrEvo and 
the conclusions of the EC SCP, was the informat ion regarding the molecular characterization of 
this product requested by the lead CA (EC-62/At.106) necessary to ensure that conclusions of the safety assessment were valid?  
Dr. Healy  
280. In 1996 AgrEvo submitted a request to the German  CA for the authorisation of the marketing 
of oilseed rape carrying the Falcon 40/90 tran sformation event.  The German CA expressed a 
favourable opinion in late 1996.  Subsequently , the request was forwarded to the European 
Commission and distributed to the Member States in December 1996.  A number of the Member 
States raised concerns and requested that additiona l information be provided.  The original dossier, 
together with additional material supplied, was considered by the Scientific Committee for Plants 
(SCP), with a favourable opinion being issued in mid 1998. 
281. Information Submitted (EC 62 – 1-30 37, 73):  The recipient oilseed rape line was 
transformed with a gene encoding the enzyme phosphinithricin acetyl transferase (PAT) from a common soil bacterium.  The PAT enzyme inactiv ates the herbicide glufosinate ammonium and 
confers herbicide tolerance to the genetically modified oilseed rape. The gene was constructed so that the regulatory sequences for the pat coding region were derived from the cauliflower mosaic virus.  
These genetic elements are well described in the litera ture and have been used to transform a variety 
of crops, both in the combination used in this case as well as in combination with other coding regions 
and/or regulatory sequences.  Furthermore, a numbe r of oil seed rape lines transformed with the pat 
gene, sometimes in combination with other genes, have been assessed for safety and approved for food use in a number of countries around the world (eg Japan
54, Australia/New Zealand55, Canada56, 
USA57 and Europe58). 
                                                      
54 http://www.mhlw.go.jp/english/topics/qa/dna/index.html. 
55 http://www.foodstandards.gov.au/whatsinfood/gmfoods. 
56 http://www.hc-sc.gc.ca/food. 
57 http://www.cfsan.fda. gov/~lrd/biocon.html.  WT/DS291/R/Add.6 
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                                                                                                                                                                      282. The molecular characterisation submitted included a sequence analysis of the pat  gene 
isolated from the soil bacterium, full DNA sequence analysis of the DNA construct containing the pat 
gene and Southern blot and Polymerase Chain Reac tion (PCR) analysis of the transgene.  The latter 
demonstrated that the pat gene was stably inserte d into two separate locations within the recipient 
strain and that vector sequences outside the border regions had not integrated.  Analysis of the 
biochemical and structural properties of the protein included heat stability, pH optimum, enzyme kinetics, inactivation studies in th e presence of gastric juices from a variety of species and under a 
variety of conditions.  These studies were conducted with the PAT protein isolated from a variety of 
transformed organisms, including an over expressing E. coli strain and maize and oilseed rape line 
transformed with the pat gene, which were demonstr ated to have similar immunological properties to 
each other.  The DNA sequence of the pat gene used  to generate Falcon GS 40/90 was compared to 
major sequence databases.  These studies also allow an  assessment of the allergenicity potential of the 
PAT protein. 
283. The PAT protein was tested for dose responsive toxicity effects in animals.  The treated 
animals were subjected to extensive analysis for toxic effects including mortality, food consumption, clinical parameters, clinical biochemistry an d pathology on an array of internal organs. 
284. The composition of fractions derived from seeds we re analysed for nutrients appropriate for 
the food (oil) and feed derivatives of oilseed rape (OECD, 2001).  The analysis addressed the key fatty acids in oil (including the toxin erucic acid) as well as nutrients and toxins in oilseed rape meal. 
285. Conclusions of the Safety Assessment:  The SCP in July 1998 (EC 62-74) concluded that 
having considered the submitted dossier and the background information available, 'there is no evidence to indicate that the placing on the market  of line transformant Falcon GS40/90 oilseed rape, 
with the purpose to be used as an y other oilseed rape, is likely to cause adverse effects on human 
health….'.  Furthermore, the SCP did not request any additional information or suggest any additional 
research in relation to the safety assessment.  It  appears that the information submitted met the 
requirements for a safety assessment as outlined  in Annex 11 B of Directive 90//220/EEC. 
286. I have reviewed the scientific information submitted and consider  that a reasonably 
comprehensive information package was developed to support the safety assessment of oilseed rape 
line Falcon GS 40/90.  The information package de veloped was consistent with internationally 
accepted approaches to the safety assessment at that time, as outlin ed above.  The information 
package addressed the three major elements that are usually cons idered in assessing the safety of a 
GM product and included molecular characterisation of the inserted gene, characterisation of the 
protein expressed by the inserted gene and an analysis of key compositional constituents relevant to 
the food product (ie oil) derived from the Falcon GS  40/90 line.  The experimental procedures were 
conducted in accordance with standard methodologies.   
287. Having examined the scientific information underpinning the safety assessment and the 
opinion of the SCP, I conclude that food (oil) de rived from oilseed rape Fa lcon GS 40/90 line is as 
safe for human consumption as food from conventional produced oilseed rape varieties.  There is no 
indication from the scientific evidence submitted for consideration by the Competent Authority that 
the food poses a health or safety risk.  Furthermore,  there is no indication of human health and safety 
issues arising from the consumption of food from other lines of oilseed rape carrying the pat gene that 
have been approved around the world and which ar e/have been in commercial production, some for 
significant periods of time.  I therefore concur with the opinion of the SCP,  issued in July 1998. 
 
58 http://europa.eu.int/comm/food/ food/biotechnology/authorisation/258-97-ec_ authorised_en.pdf. WT/DS291/R/Add.6 
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  288. The Lead CA sought addition information (EC 62-106): 
• on the DNA sequences flanking the transgene locus in Falcon GS 40/90 (ie spanning 
the left and right junctions between  the inserted DNA and the plant DNA), 
• comparison of these DNA sequences with those of the pre insertion site in 
nontransformed lines, preferably from the Falcon variety. 
289. The information on the flanking sequences is lik ely to provide a full se quence analysis across 
DNA junction between the genomic DNA and the inserted DNA (pat gene).  Such information can be 
used to analyse the DNA for potential novel protei ns that may be generated as a result of the 
juxtapositioning of the different segments of DNA.   
290. Such information will also provide a more detaile d description of parts of the structure of the 
transgene that was actually inserted into the genom ic DNA, facilitating the identification of any small 
rearrangements or other modifications to the DNA th at may occur during the transformation process.  
Some transformation techniques are more prone th an others to generating such modifications. 
291. Comparison of the insertion sites in the transformed line with that of its parental non 
transformed line may give additional information about any minor DNA changes at these sites (eg 
rearrangements, deletions).  It may also reveal other nucleotide changes (polymorphisms) that are a 
result of natural variation between individuals within lines and which are not related to the 
transformation process. 
292. Impact of the Additional Information on the C onclusions of the Safety Assessment:  The 
additional information requested by the Lead CA is unlikely to influence the conclusions of the safety 
assessment carried out by the SCP.  The rationale for this view are: 
• The transgene was inserted into the Falcon GS40/90 line via agrobacterium mediated 
transformation techniques.  This technique is less likely to result in DNA rearrangements and other modifications of the inserted DNA, compared to some other transformation techniques (eg micro projectile bombardment).  The molecular characterisation provided by AgrEvo does not indicate that any modifications to the 
structure of the inserted DNA have occurred although the possibility of small 
modifications that cannot be detected by Southern blot analysis cannot be entirely 
excluded.  This is well exemplified by the example of Roundup Ready soybean, for which the initial molecular ch aracterisation did not reveal any modifications in and 
around the inserted gene, although subseque nt sequence analysis revealed the 
presence of additional DNA fragments (Windels et al, 2001). 
• The molecular characterisation originally submitted did include a PCR analysis, which indicated that only the DNA sequences associated with the pat gene had integrated into the recipient strain.  In pa rticular, the analysis verifies that that no 
sequences from the vector, others than intende d, integrated into the recipient strain. 
• Additional information of the sequences at the sites of insertion may reveal fine 
structural details and identify similarities and differences with the parental line at 
these sites.  Such detailed structural analyses usually aim to provide an indicator of 
unintended effects from the genetic modification.  However, in some cases it may be 
difficult to determine the biological signif icance of any sequence differences because 
of a lack of knowledge about the extent of sequence variation between individual organisms within the parental line.  Furthermore, other indicators of unintended effects, that are biologically meaningful, are obtained from other elements of the safety assessment (eg analysis of protein, composition of food).  WT/DS291/R/Add.6 
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  • A comprehensive package of informati on was provided that addressed the key 
elements required in a safety assessment and there was no indication of any safety 
issues when all the available data was take n into account.  Furthermore, the pat/PAT 
gene/protein is well characterised, has been  utilised successfully in a number of crops 
and their resultant food products and w as derived from a well described organism. 
293. Conclusion:  The additional molecular characterisation requested by the Lead CA is unlikely 
to affect the conclusions of the safety assessment and was not necessary to ensure that the conclusions of the safety assessment were valid.  The totality of in formation provided in the dossier to that point in 
time were adequate to support the validity of the conclusions of the safety assessment without the 
need for the additional data requested  in the letter dated 2 April 2002. 
Dr. Snape  
294. The comments below relate to Question 12 concerning the molecular characterisation of 
exhibit EC-062.  These were examined relative to the EFSA-Q-2003-005 guidance document produced by the Scientific Panel on Genetically Modified Organisms. 
295. Exhibit EC-062:  Oilseed rape event Falc on GS40/90 (also named GS40/90pHoe6/Ac) was 
produced, using plasmid pHoe6/Ac, by means of Agrobacterium-mediated gene transfer. The T-DNA of the plasmid pHoe6/Ac used for transformation carries a chimeric pat expression unit conferring resistance to the herbicide glufosinate. Oilseed rape event GS40/90pHoe6/Ac  contains two functional 
transgenic loci. Both transgenic loci will be present in the commercialised GM plants. Information relative to the molecular characterisation of GS40 /90pHoe6/Ac has been found primarily in EC-062 
attachments 3, 13, 14, 113, 114. A series of commen ts and questions are numbered below. This is  
followed by a conclusion proposing answers to Question 12. 
296. The molecular characterisation of GS40/90pHoe6/ Ac initially provided was not complete and 
failed to identify the exact transgenic make-up of th is GM plant. Initially, two intact copies of the 
CaMV35S:pat:35T expression unit were  believed to be inserted at tw o independent f unctional loci 
(EC062 attachment 3 and 14). Later it was determin ed, following requests for additional information, 
that in fact one of the two functional loci contained two CaMV35S:pa t:35T expression units in 
inverted tail-to-tail orientation (EC062 attachment  114) bringing the total copy number of  the pat 
gene to three in GS40/90pHoe6 /Ac. This re-emphasizes the need, expressed in general comment 2 
(accompanying document) by this Expert, to conduct independent molecular analyses for each 
transgenic locus present in a GM plant. This also means that two sets of full molecular analyses are 
expected to be provided, one for each tran sgenic locus present in GS40/90pHoe6/Ac.   
297. The segregation analysis of transgene phenotyp e indicates the presence of two functional loci 
in GS40/90pHoe6/Ac but does not account for n on-functional transgenic sequences potentially 
inserted into additional genomic location (i.e. third transgenic locus). An inheritance study, based on 
the presence or structure of transgenic sequences in  progeny plants should be conducted to confirm 
that only two transgenic loci are present in GS40/90pHoe6/Ac (see comment 3 in accompanying 
document).  
298. EC062 – Attachment 3:  The text cross-refere nce annexes that are not included in this 
attachment. This reviewer assumed that annex 8 and 9 corresponded to attachment 13 and 14.  
299. EC062 – Attachment 13:  Only a partial sequenc e of the pHoe6/Ac vector (including the T-
DNA region and surrounding vector sequences) is provided. Attachment 13 (annex 8) does not 
provide information about the "insert" as stated in  page 16 section 30a and 30b of attachment 3.  WT/DS291/R/Add.6 
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  300. EC062 – Attachment 14:  The Southern blot analyses do not provide definitive answers about 
the total number of copies of transgenic seque nces introduced into GS40/90pHoe6/Ac. Further 
analyses (attachment 113, 114) will show that an additi onal copy to the two identified here are in fact 
inserted into the nucleus of GS40/90pHoe6/Ac.  
301. EC062 – Attachment 74:  This Expert disagre es with the comments in paragraph 6.1.3 
"Transgenic construct in the GM plant". So far, th e data presented only show that two functional loci 
are present in GS40/90pHoe6/Ac. No structural analysis of progeny has been conducted to 
demonstrate that only two transgenic loci were present and that each locus was structurally stable. The 
Southern blot analysis presented in attachment 14 (see above) does not provide information about the 
structure of each of the two transgenic loci. The use of the term "insert" is here again confusing as the 
sentence "It is shown that the insert is stable a nd follows standard Mendelian inheritance" means in 
fact that two functional loci have been identified and that the segregation of transgene phenotype (i.e. 
herbicide tolerance) across generations is compatible  with two functional Mendelian loci. This is not 
completely informative about the structural stability  or the number of transgenic loci (with the 
exception that there is at least two of them).  
302. EC062 – Attachment 113:   Page 70 of the PDF file and onwards, what is "transgen" In 
figures 1,2,3,5,6,7? Does "transgen" mean line GS40/90pHoe6/Ac? 
303. EC062 – Attachment 113:  This attachment c ontains, among many other documents, the study 
A59211 entitled "Southern analysis performed on the gl ufosinate tolerant 6Ac rape line". This Expert 
disagrees with the conclusion of this study that "no region outside the two border sequences of the 
binary vector pHoe6/Ac are integrated into the geno me of the 6Ac rape line" stated page 69 of the 
PDF file. The Southern blot analyses undertaken in this study seem to have been conducted on a rape 
line containing only one copy of the CaMV35S:pa t:35T expression unit integrated into the plant 
genome (the XbaI/XhoI digest hybridized with th e pat gene produces only one band in figure 5). This 
is not compatible with the fact that GS40/90pHoe6/ Ac contains at least two functional loci (i.e. at 
least two copies of the expression unit). Further molecular analyses should be conducted using 
restriction enzymes which cut only once into the T-DNA and using the same set of probes 1,2,3,4 and pat.   
304. EC062 – Attachment 114:  Page 5 should read "three copies of the T-DNA are inserted in 
oilseed rape event falcon GS40/90 at two indepe ndent functional loci. It  was shown that the 
expression of the insert is stable and follows Mende lian inheritance". In the absence of molecular 
analysis of the progeny plants, the exact number and stability of transgenic loci cannot be established.  
305. EC062 – Attachment 114:  The full sequence of the transgenic locus EE1 is provided with 
flanking genomic sequences providing a full and optimal characterisation of this locus. 
306. EC062 – Attachment 114:  The sequence of the transgenic locus EE2 should be provided, 
especially as it contains a combination of two T-DNAs . This reviewer could not locate the southern 
blot analyses underlying the architecture proposed for EE2.  
307. Conclusion – Response to Question 12:  Since the first submission in 1996, the following 
molecular information about GS40/90 pHoe6/Ac has been established: 
• GS40/90pHoe6/Ac contains two independen t functional loci, named EE1 and EE2; 
• The locus EE1 and its plant genomic flanki ng regions have been fully sequenced and 
characterised. One copy of the CaMV35S:p at:35T expression unit is present in EE1;  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-69 
 
 
  • The locus EE2: A structural organisation involving two CaMV35S:pat:35T 
expression units in tail-to-tail orientation has been proposed and plant genomic flanking regions have been sequenced.  
308. For a full molecular characterization to satisfy all regulatory requirements, this Expert would 
suggest that more informa tion is still required about: 
• The locus EE2: the Southern blot data supporting the structural organisation of this locus could not be found by this reviewer. It would be desirable to sequence the EE2 
locus in order to provide the same type of complete information already available for the EE1 locus. 
• The molecular analysis of GS40/90pHoe6/ Ac for the presence of unwanted backbone 
sequences needs to be re-visited as inconsiste ncies appear in the current analysis (see 
attachment 113  – the plant analysed seems  to contain only one pat transgene copy 
and not three as expected from GS40/90pHoe6/Ac). 
309. The structural analysis of progeny plants is required to ensure that no additional transgenic 
sequences have been integrated in other genomic locations and that EE1 and EE2 are structurally 
stable across generations. 
310. Additional information may have submitted to the EC by the company. Is so, it should be 
examined to see if it answers some of the requests formulated above. 
Question 13:  Given the information before the Pa nel, including the notification by AgrEvo and 
the conclusions of the EC SCP in relation to the potential persistence or invasiveness of Bayer oilseed rape (Falcon GS40/90), would this produc t qualify as a potential "pest" as the term is 
used in ISPM 11?  
Dr. Nutti  
311. According to the International Plant Conve ntion's (IPPC) International Standard for 
Phytosanitary Measures (ISPM 11) in EC-130, the defin ition of pest is "Any species, strain or biotype 
of plant, animal or pathogenic agent injurious to plant or plant products".  In my opinion, Bayer oilseed rape (Falcon GS40/90) cannot be qualified as  a potential "pest", according to this definition. 
Dr. Andow  
312. This question is a special case of the general c ase covered in my answer to question 6.  My 
answer to question 6 holds in this special case.  Sp ecifically, it appears that on the issue of persistence 
that the SCP did not explicitly consider the issue of release rate or scale, nor did it determine whether contamination of conventional varieties was an inju ry to plants.  Indeed, the data presented by the 
notifier, the argument of the notifier, and the argum ent implicit in the SCP Opinion all suggest that 
scale was not considered.  Hence the SCP Opinion must be considered incomplete for allowing a determination of "pest" status.  I conclude that the pest status of Falcon GS 40/90 cannot be determined based on the information before the Panel. 
Dr. Snow  
313. I conclude that in some situations, this product qualifies as a potential "pest", as I discuss in 
Answer 6.  If the herbicide glufosinate becomes used more widely, as expected, volunteers and weedy WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  Brassica rapa that develop resistance could qualify as worse "pests".  However, this problem should 
be manageable over the short term by using other methods of weed control. 
Dr. Squire  
314. In that oilseed rape as a volunteer or feral plant is a pest as defined in ISPM 11, e.g. a weed 
competing with a crop for resources, and having ot her potential influences, the Bayer oilseed rape 
(Falcon GS40/90) has the potential to be a pest, si nce it would leave volunteer and feral descendents. 
Whether it would be more or less a pest than othe r forms of oilseed rape depends on whether it would 
be sprayed as a volunteer or feral with the herbicide glufosinate ammonium (see Responses 6b-c). 
That would be context-specific, e.g. whether farm ers in the region or country used this specific 
herbicide widely or repeatedly in fields. 
Bayer hybrid oilseed rape (MS8/RF3)  
C/BE/96/01  (EC chronology 63)  
Question 14:  Given the information before the Pa nel, including the conclusions of the EC SCP 
(EC-63/At.54) in relation to the potential persi stence or invasiveness of Bayer hybrid oilseed 
rape (MS8/RF3), would this product qualify as a po tential pest according to ISPM 11?  If so, are 
the proposed post-market monitoring plans consistent with the monitoring and review 
principles described in ISPM 11?  
Dr. Nutti  
315. According to the International Plant Conve ntion's (IPPC) International Standard for 
Phytosanitary Measures (ISPM 11) at EC-130, the definition of pest is "Any species, strain or biotype 
of plant, animal or pathogenic agent injurious to plant or plant products".  In my opinion, Bayer oilseed rape (MS8 / RF3) cannot be qualified as a potential "pest", according to this definition. 
Dr. Andow  
316. Regarding the definition of potential pest, this question is answered more generally in my 
response to question 6.  That answer applies to this particular case.  Specifically, it appears that on the issue of persistence that the SCP did not explicitly consider the issue of release rate or scale, nor did it determine whether contamination of conventional varieties was an injury to plants.  Indeed, the data 
presented by the notifier, the argument of the notif ier, and the argument implicit in the SCP Opinion 
all suggest that scale was not considered.  Hence th e SCP Opinion must be considered incomplete for 
allowing a determination of "pest" status.  I conclu de that the pest status of MS8/RF3 cannot be 
determined based on the information before the Panel. 
317. The need for risk management and monitoring  was outlined in the SCP (EC-63/At.54, 19 
May 1998) as follows:   
2.  The Committee was also of the opinion th at the potential transfer of the herbicide 
resistance gene to wild Brassica relatives is a new issue in Europe in view of the 
limited scale of release to date.  The Comm ittee has examined the available evidence 
from monitoring and research programmes to date.  After evaluating all the information available to the Committee, it was concluded that herbicide-tolerant 
volunteers that may appear would be canola plants and not wild Brassica relatives.  
Such herbicide-tolerant volunteers could be controlled in subsequent crops by  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  conventional agricultural methods.  The Co mmittee recommends that the introduction 
of herbicide-tolerant crops  should be accompanied by: 
i)  an agreed code of practice for the particular modified crop involving the active 
participation of the notifier to promote best practice by farmers. 
ii)  a monitoring programme with an agreed  design and implementation plan to detect 
the occurrence and the establishment of herbicide-tolerant volunteers and weeds 
under field conditions in the EU. 
318. The SCP is recommending a "code of practice" in order to ensure that herbicide-tolerant 
volunteers are eliminated.  In other words, the purpose of the risk management measure is to eliminate 
volunteers as they occur.  In addition, it is re commending research design and implement monitoring 
to detect herbicide-tolerant volunteers and herbicide-tolerant weeds in the EU.   
319. In addition, the objectives of Annex VII, Directive 2001/18/EC also are relevant and are 
acknowledged as such by the notifier (EC-63/At.124, p. 6). 
320. The notifier proposes a two-part monitoring  system: case-specific monitoring for HT 
volunteers and HT weeds, and general surveillance fo r unanticipated effects (EC-63/At.124, p. 7ff).  
These parts are intended to meet the concerns expressed by the SCP and the objectives of Annex VII. 
321. Section 3.6.1 of ISPM 11 describes the monitoring and review of phytosanitary measures.  
This concentrates on the principle of "modification", and is repeated here. 
3.6.1 Monitoring and review of phytosanitary measures 
The principle of "modification" states:  "As conditions change, and as new facts become available, phytosanitary measures shall be modified promptly, either by inclusion of prohibitions, restrictions or requirements necessary for their success, or by removal of those found to be unnecessary" (ISPM N° 1:  Principles of plant 
quarantine as related to international trade ). 
Thus, the implementation of particular  phytosanitary measures should not be 
considered to be permanent.  After app lication, the success of the measures in 
achieving their aim should be determined by monitoring during use.  This is often achieved by inspection of the commodity on arrival, noting any interceptions or any entries of the pest to the PRA area.  The information supporting the pest risk analysis 
should be periodically reviewed to ensure  that any new information that becomes 
available does not invalidate the decision taken. 
322. This suggests that an important part of th e risk management measures applied to GMHT 
crops should include a process of review of the ne cessity of the management measures.  Additional 
general issues are discussed in my response to question 6. 
323. The notifier has proposed a review process in the monitoring plan (EC-63/At.124, p. 21), 
which is repeated here. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-72 
  
  Review  
This monitoring plan will be revised along with the expertise acquired.  The 
monitoring plan and its associated methodology will be reviewed at the end of each 
growing season and updated as necessary in  light of results obtained during the 
monitoring programme.  Reviews will examine the effectiveness and efficiency of 
data measurements and collection in order to  be able to improve the quality of the 
monitoring programme. 
324. In addition, the notifier proposes to terminat e case-specific monitoring after five years. 
325. Thus, I conclude that the proposed post-marke t monitoring plans are consistent with the 
monitoring and review principles described in ISPM 11.  The proposed plans are the most thorough 
and well-considered of any of the monitoring pl ans in the material before the Panel.   
326. However, I also believe that the proposed plan could be much improved so that it is not 
merely consistent with ISPM 11 but actually meets the full intent of ISPM 11. 
Dr. Snow  
327. I conclude that this product could qualify as a potential pest, as I discuss in Answers 6 and 13.  
If the herbicide glufosinate becomes widely used, as expected, glufosinate-resistant volunteers and 
weedy Brassica rapa could become worse pests.  Ho wever, this problem can be managed using other 
methods of weed control.  (note: the EC SCP conclusions about risks dealing with gene flow, 
volunteers, and wild relatives are the same as tho se for Bayer oilseed rape, above, with the same 
shortcomings; see Answer 11). 
328. The ISPM 11 monitoring and review principles (section 3.6.1) discuss the need to modify 
phytosanitary measures as needed  when new information becomes available.  The post-marketing 
monitoring plans that are proposed by the notifi er are consistent with these principles.  If 
implemented, these plans would be useful for detecting the spread of glufosinate resistance to 
volunteer plants and wild relatives.   
329. Caveat – The monitoring plans do not address broader concerns about monitoring for changes 
in biodiversity in and around farmland as a result of more efficient and extensive weed control, and 
they do not provide unique identifying markers for monitoring gene flow (e.g., these issues are 
discussed in the May 2004 Danish position; EC-063 At. 173). 
Dr. Squire  
330. The basic answer is similar to that given for Q.13.  A few statements need comment, 
however. The EC SCP (EC-63/At.54, section 6.3.1) gave the opinion that "rape is a poor competitor" 
and "not regarded as an environmentally-hazardous colonising species", and while the latter is still 
probably acceptable in semi-natural ha bitats, the continued widespread persistence of oilseed rape in 
and around arable fields, both from original seed and from re-seeding, points to its competitive ability 
being greater than "poor" but similar to many second -order weeds (i.e. weeds that are less important 
than the most aggressive few species but are still important).  The proposed post-marketing 
monitoring plans (EC-63 At.060) are generally consistent with the principles in ISPM 11, but do not 
give specific detail on, say, how a field is to be sampled to estimate % GM presence among 
volunteers with a stated degree of certainty (see Responses 6e and 9).  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-73 
 
 
  Question 15:  Given the information before the Pane l, including the conclusions of the EC SCP, 
was the information regarding the assessment of the long-term effect of the newly expressed 
protein on the biogeochemical cycle and the food chain requested by the Italian CA 
(EC-63/At.87) necessary to ensure that conclu sions of the safety assessment were valid? 
Dr. Nutti  
331. Based on the information provided by the appli cant (EC-63/At.01 to 176) and the analysis 
done by the EC SCP presented in CDA-35A and EC-063/At.54, the information presented in CDA-56 
and following the Codex Guidelines, my understandi ng is that the request by the Italian CA (EC-
63/At.87) was not necessary to ensure the conclusions for the safety assessment of the newly expressed protein in the food chain. As pointed out by the EC SCP in item 6.2 – Safety Aspects, there are no antibiotic resistance marker genes in this GM O. The bargene is controlled by a plant promoter 
which is not functional in bacteria. Conseque ntly, its expression in the unlikely event of 
transformation would not occur. Even if, due to ge netic recombination, the gene would be expressed 
in intestinal micro-organisms or human or animal cells, the probability of which is remote, no negative effects are expected b ecause the only known substrate of the enzyme phosphinothricin 
acetyltransferase PAT is the herbicide glufosinate ammonium. 
332. The PAT protein has been detected in very  low amounts in dry seed (0.1 mcg/mg seed 
protein). As almost no protein is present in the oi l extracted from the plants, the risk for human 
consumption is non existent. The amounts of PAT (t he new protein) present in the seed-meal fed to 
animals would be too low to cause even theoretical concern. The low amount of PAT protein in vegetative tissues of the plants is an additional gua rantee of safety in case of occasional consumption 
of the green parts of the plant by farm or wild an imals. The low levels of PAT protein and the weight 
of evidence available elsewhere c oncerning the safety of PAT leads the Committee to conclude that 
there is no significant risk to humans or livestock following the ingestion of the gene product.  
333. Compositional analysis were carried out on the seed harvested from the original plant lines, 
their hybrids, and lines developed from them by mu ltiple backcrosses to different oil seed rape 
varieties from field trials in Europe and North America, where locally adapted commercial varieties were used as controls. Information on fat content, gl ucosinolate levels, fatty acids profiles (including 
erucic acid), vitamin E and mineral content showed  no differences which could be attributed to the 
genetic modification, leading to the assumption that no significant changes in nutritional value have 
been identified.  
334. I agree with item 7 of the Overall Assessment, where the EC SCP states that there is no 
evidence to indicate that the placing on the market of hybrid seed of sweed rape (consisting of 
crossing of parentals derived from genetically m odified sweed rape lines MS8 and RF3) with the 
purpose to be used as any other sweed rape is lik ely to cause any adverse effects on human health. 
Based on the scientific evidences presented, my understanding is that the new protein is safe for consumption in the food chain. 
Dr. Andow  
335. In EC-63/At.87, 14 March 2000, the Italian CA requested the following information. 
Referring to the conclusion of the last meeting of the Regulatory Committee under Directive 90/220/EEC, Italy would be very pleased to receive from the notifier more 
information concerning the assessment of the effect of the genic product on the WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-74 
  
  biogeochemical cycles and on food chain and on the apreading of the gene due to the 
possibility of crossing between the PGM and wild species. 
336. This is an identical request for information on  the same date as for Falcon GS 40/90 (EC-
62/At.95).  Even without looking into the specifics of this case, my genera l comments on this request 
to the notifier of Falcon GS 40/90 in my response to question 10 in paragraph 252 also holds in this 
case. 
337. The Italian CA made the request on 14 Ma rch 2000.  The notifier provided an updated 
notification on 10 November 1999, which was circulated to the CAs on 13 December 1999.  The 
notifier provided additional information on 25 Febr uary 2000 and 1 March 2000.  Except for the dates 
that additional information was provided, this is  the same timeline as Falcon GS 40/90, and my 
conclusion in paragraph 256 holds here. 
Question 16:  Given the information before the Panel, including the conclusions of the SCP, was 
the information regarding molecular characterizati on of this product requested by the lead CA 
(EC-63/At.107) necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Healy  
338. Following receipt in September 1996 of the notification from Plant Genetic Systems (PGS, 
now Bayer Crop Science) seeking approval for oilseed rape lines MS8 and RF3, the lead CA (Belgium) expressed a favourable opinion in January 1997. The dossier was then sent to the European 
Commission and distributed to other Member States for comment. Supplementary information from 
PGS required by Member States was added to the dossier, which was submitted to the SCP for 
assessment. In May 1998, the SCP also expressed a favourable opinion on MS8, RF3 and hybrid MS8xRF3 lines with respect to human health and safety.  
339. Background:  The two oilseed rape lines under c onsideration, MS8 and RF3, both contain a 
bacterial gene, pat, that confers tolerance to  the herbicide phosphinothricin, also known as 
glufosinate-ammonium. The presence of the pat gene enables the rape plants (Brassica napus) to produce an enzyme, phosphinothricin acetyl transferase (PAT), which chemically inactivates the herbicide, allowing the plants expressing the PAT protein to function normally in the presence of the herbicide. The pat gene was used as a selectable mark er gene in the individual lines and also to confer 
tolerance to commercial applications of glufosinat e-ammonium herbicide in MS8/RF3 hybrids. There 
were no other marker genes used and there are no antibiotic resistance genes in either MS8 or RF3. 
340. In conjunction with the herbicide tolerance trait, MS8 contains another bacterial gene, 
barnase. Expression of barnase in specific parts of the flower at a particular developmental stage gives rise to plants that do not produce pollen (male-st erile, MS). The barnase gene prevents pollen 
formation by producing a non-specific ribonuclease that destroys the tapetal cell layer in which it is expressed.  
341. The RF3 line contains the corresponding bacteria l gene, barstar, as well as the herbicide 
tolerance trait. Expression of the barstar gene in the same floral tissues, the tapetal cells, produces a 
protein that specifically binds and inactivates the barnase, thereby restoring normal pollen production. Hybrid MS8/RF3 plants are phenotypically normal and fully fertile. The primary objective of the modifications in MS8 and RF3 is to generate pollin ation-controlled parental oilseed rape lines with 
superior agronomic performance for use in a breeding system that generates hybrids with significantly 
higher seed yields.   WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-75 
 
 
  342. Molecular characterisation data:  PGS submitted a range of company studies on the molecular 
characterisation of MS8 and RF3 lines in its origin al dossier. These data were consistent with the 
approach generally considered appropriate at the ti me for the assessment of the safety of transgenic 
crop plants and derived food products  intended for human consumption.  
343. Descriptions of the plasmids pTHW107 and pTHW118 used to generate the MS8 and RF3 
lines respectively were provided, including the size,  source and function of the transgenes and their 
regulatory elements. In addition to  standard Southern blot hybri disation analyses that generate 
information on the number and size of insertions, the data included DNA primer sequences, PCR 
methods for analysing the specific insertion ev ents, and detailed DNA sequence analyses of the 
integration region in both lines. The CA (Belgium) declared in 1997 that the data provided showed 
that the transgenes in lines MS8 and RF3 are not in serted into a known functional plant gene (EC 063, 
attachment 007). 
344. Approximately 4900 base pairs (bp) of the inserted DNA sequence in MS8 was provided, 
showing exact similarity with the transforming plas mid sequence between the left and right borders of 
the T-DNA, with no deletions or rearrangements. Flanking nucleotide sequence was provided at the 
5'end (864 bp) and the 3'end (357 bp) of the inser ted DNA.  These flanking sequences were analysed 
for homology with known sequences. Part of the 5' flanking sequence showed some degree of 
similarity with published sequences from Arabidops is thaliana chromosomes 5 and 3. However, no 
homology with known sequences was found  using the 3' flanking sequence. 
345. The DNA sequencing analyses of RF3 showed that the inserted DNA corresponds exactly 
with the transforming plasmid, however from the data  it was evident that an inversely-oriented second 
partial fragment of T-DNA was present at the left bo rder of the introduced DNA at the same insertion 
site. The second copy includes a functional part of the anther specific TA-29 promoter, the coding 
region of the barstar gene, 3' nos  termination sequence and a non-func tional part of the PssuAra with 
the T-DNA sequence ending 750 bp upstream of the ATG initiation codon of the bar gene. Detailed 
nucleotide sequencing across the integration sites ge nerated 1077 bp at the right border, 1457 bp at the 
inverted repeat junction, and 1501 bp at the left  border. Approximately 8900 bp corresponding to the 
entire RF3 insertion event was determined. Flanking  nucleotide sequence was provided at the 5' end 
(812 bp) and at the 3' end (1275 bp) of the inser ted DNA. These flanking sequences were analysed for 
homology with known sequences. Parts of the 3' flan king sequence showed some degree of similarity 
with published sequences from Arabidopsis thaliana  chromosomes 1 and 5. However, no significant 
homology with known sequences was found using the 5' flanking sequence.  
346. Conclusions of the Safety Assessment:  The SC P considered in 1998 that the data submitted 
in the dossier was satisfactory concerning information on the transformation techniques, vector constructs, insertion event in the transgenic plan ts and transgene and cryptic gene expression. The 
overall assessment and conclusion of the SCP was that 'there is no evidence to indicate that the placing on the market of hybrid seed of swede rape (consisting of crossings of parentals derived from genetically modified swede rape lines MS8 and RF3)  with the purpose to be used as any other swede 
rape is likely to cause adverse effects on human health and the environment'. 
347. Additional Information Sought by Lead CA:  Although junction regions at the sites of 
integration in the transformed lines were separately cloned and sequenced, there was minimal DNA 
sequence data generated from the wildtype isogenic lines at the corresponding locus. Consequently, 
the submitted homology searches were performed using sequence data obtained only from the 
transgenic lines. Subsequently, molecular details of  the flanking regions were not considered to be 
adequate by the lead CA and the results of further PCR and sequence analyses were sought.  WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-76 
  
  348. Impact of Additional Information on the C onclusions of the Safety Assessment:  The 
additional molecular characterisation data sought by the lead CA in 2002 were not required to 
demonstrate the safety of food products derived from MS8, RF3 or MS8xRF3 hybrid lines. The 
rational for this view are: 
• Finely detailed molecular analysis of a defined chromosomal region in commercially 
adapted plant lines such as oilseed rape is likely to reveal minor nucleotide 
differences between various lines that have no significance with respect to the safety 
of derived food products. In the absence of  an equivalent nucleotide analysis from a 
number of commercial food-producing oilseed rape lines, these data do not contribute 
substantially to the bank of information th at is necessary to adequately characterise 
MS8 and RF3 at the molecular level. Moreover, it is not clear how such data should 
be interpreted in an assessment of transgenic plants.  
• The data provided at that point in time  (i) allowed adequate description of the 
insertion events in both transgenic lines, (ii) was sufficiently detailed, presented 
clearly and of acceptable quality, and (iii) was consistent with a generally accepted 
approach to the molecular characterisation of transgenic crops used for food 
production.  
• The most significant elements of the assessment of MS8 and RF3 oilseed rape lines more appropriately focus on the molecular characterisation of the insertion events and 
the resultant novel gene products, particularly  in terms of their potential toxicity and 
allergenicity. The food products derived from transgenic oilseed rape are likely to 
contain at most only trace amounts of plant proteins due to processing. Comparative compositional data from the seeds of bot h transgenic lines and the corresponding 
isogenic lines therefore provides necessary information to determine unintended effects.  
349. Conclusion: The totality of information provided in the dossier to that point in time contained 
sufficient information to support the validity of th e conclusions of the safety assessment without the 
need for the additional molecular ch aracterisation data requested in the letter of the Biosafety Council 
dated 28 March 2002.  
Dr. Snape  
350. The comments below relate to Questions 16 and 18 concerning the molecular characterisation 
of exhibit EC-063.  These were examined relative to the EFSA-Q-2003-005 guidance document 
produced by the Scientific Panel on Genetically Modified Organisms. 
351. Oilseed rape event Ms8 was produced, using plasmid pTHW107, by means of 
Agrobacterium-mediated gene transfer. The T-DNA of the plasmid pTHW107 used for transformation carries two expression units: one contai ns the bar gene, conferring resistance to the 
herbicidial compound glufosinate and one contains the barnase gene to engineer male sterility. A 
barstar gene (driven by a bacterial promoter) is  also present in the backbone of pTHW107. Oilseed 
rape event Ms8 is described as containing one functi onal transgenic locus containing one copy of the 
pTHW107 T-DNA.   
352. Oilseed rape event Rf3 was produced, using pl asmid pTHW118, by means of Agrobacterium-
mediated gene transfer. The T-DNA of the plasmid pTHW118 used for transformation carries two expression units: one contains the bar gene c onferring resistance to the herbicidial compound 
glufosinate and one contains the barstar gene to engineer fertility restoration. An additional copy of the barstar gene (driven by a bacterial promoter) is also present in the backbone of pTHW118. Oilseed  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-77 
 
 
  rape event Rf3 is described as containing one functio nal transgenic locus containing two copies of the 
pTHW118 T-DNA in inverted orientations, one copy of the T-DNA being intact the other one being 
partially deleted.   
353. Information relative to the molecular charact erisation of Ms8 and Rf3 has been found 
primarily in EC-063 attachments 4, 19, 20, 43, 54, 98, 114, and 115. A series of comments and questions are numbered below. This is followed by a conclusion proposing answers to Questions 16 
and 18: 
354. EC063 – attachment 001:  (1) Contains only the ta ble of content of the initial notification. The 
data corresponding to the molecular analysis in part1 section III and IV (pages 7 to 20) were not 
found by this Expert in subsequent attachments. When requested, this info rmation was not available 
from WTO either. It is likely that some relevant information was initially submitted by the company. 
However in its absence this Expert cannot determine: 
(1a) The sequence of pTHW107 and pTHW118  
(1b) If oilseed rape event Ms8 contains only one copy of the bar gene and one copy of the 
barnase gene.  
(1c) If oilseed rape event Rf3 contains only one  copy of the bar gene and two copies of the 
barstar gene. 
355. EC063 – attachment 019 and 020:  Presents a PCR analysis suggesting the absence of Sm/Sp 
antibiotic resistance gene in Ms8 and Rf3. 
356. EC063 – attachment 043:  Presents a Southern blot analysis demonstrating the absence of 
vector backbone sequences into Ms8 and Rf 3 including the bars tar gene in Ms8. 
357. EC063 – attachment 098:  The transgenic locus in Ms8 and its plant ge nomic flanking regions 
have been fully sequenced and analysed providing an  optimal characterisation of this locus. This 
transgenic locus contains one copy of the pTHW107 T-DNA.  
358. The transgenic locus in Rf3 and its plant genomic flanking regions have been fully sequenced 
and analysed providing an optimal characterisation of this locus. This transgenic locus contains two 
copies of pTHW118 T-DNA in inverted orientations , one copy of the T-DNA being intact the other 
one being partially deleted.  
359. Conclusion – Response to Questions 16 and 18:  Additional information may have been 
submitted to the EC by the company (see point 1a, 1b, 1c above). Experts should examine if this 
information answers some of the requests formulated below. 
360. Ms8:  Since the first submission in 1996, the following molecular information about Ms8 has 
been established: 
• Ms8 contains one transgenic locus (if conf irmed by Southern analysis see point 1b). 
• This locus and its plant genomic flanking regions have been fully sequenced and 
characterised. One copy of the pTHW 107 T-DNA is present at this locus. 
• Transgenic sequences outside the T-DNA of pT HW107 have not been integrated into 
Ms8. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-78 
  
  361. This Expert concludes that no more informati on is required (if Southern analysis confirm 
point 1b). As Ms8 contains a single copy of the bar and barnase gene, the monitoring of transgene 
expression across generations provides a satisfactory estimation of the transgenic locus structural 
stability and inheritance.  
362. Rf3:  Since the first submission in 1996, the following molecular information about Rf3 has 
been established: 
• Rf3 contains one transgenic locus (If confir med by Southern analysis see point 1c). 
• This locus and its plant genomic flanking regions have been fully sequenced and 
characterised. Two copies of the pTHW118 T-DNA in inverted orientations are 
present at this locus, one copy of the T-DNA being intact the other one being partially 
deleted.   
• Transgenic sequences outside the T-DNA of pTHW118 to have not been integrated 
into Ms8. 
363. In the opinion of this Expert, to satisfy all re gulatory requirements, more information is still 
required about the structural analysis of progeny plants to ensure that the transgenic locus is 
structurally stable across generations. As Ms8 cont ains two copies of the barstar gene the monitoring 
of transgene expression across generation is not in formative on the stability and inheritance of the 
transgenic locus.  
Question 17:  Were detection meth ods commercially available in 2001 sufficient to enable the 
detection of the transgenic proteins expressed by  the plant line hybrid oilseed rape MS8/RF3? 
Given the information before the Panel, including the SNIF (EC-63/At.109) and the updated 
environmental risk assessment (EC-63/At.110-14 0), was additional information regarding a 
quantitative detection method (EC-63/At.141) necessa ry to ensure that conclusions of the safety 
assessment were valid? 
Dr. Nutti  
364. A qualitative method available at the time. EC-063/At.141 asks for a quantitative event 
specific detection tool for elite events and hybrids.  It is recognized that a qualitative detection method 
and reference materials were provided by the co mpany. Based on the information provided at CDA-
56, I can infer that there was no general validation of the method used by the notifier. So far, only 
DNA extracted from unprocessed raw mate rial has been tested. It was observed that this detection 
method should also be demonstrated to work usi ng other matrices. Further, the sensitivity of the 
detection method should still be assayed by testing th e presence of the elite or hybrid events in mix 
samples. Finally, based on the given method, one can not make a distinction between the hybrid and a 
mixture of the two parental lines. My conclusi on is that the method presented was technically 
sufficient for the safety assessment, although it would have to be validated. 
365. Although a quantitative method will provide rele vant information for labelling and to the 
consumer, it is not necessary to ensure the validity of the safety assessment. It is important to point 
out that the EC SCP has considered that there is no evidence to indicate that the placing on the market 
of hybrid seed of oilseed rape (c onsisting of crossing of parentals derived from genetically modified 
oilseed rape lines MS8 and RF3) with the purpose to be used as any other oilseed rape is likely to cause adverse effects on human health.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-79 
 
 
  Dr. Healy  
Question 17 – part 1 : 
 
366. The transgenic oilseed rape lines MS8 and RF3 are developed specifically to generate high 
yielding seed produced by the MS8xRF3 hybrid. Fo od products intended for human consumption are 
therefore derived from the hybrid seed rather than from the individual parental lines. Novel transgenic 
proteins expressed in the hybrid plants include th e PAT protein (herbicide tolerance), and the two 
bacterial proteins barnase and barstar (for pollinatio n control in the parental lines). The patterns and 
levels of gene expression conformed to those pred icted and intended by the modification process. 
367. The SCP acknowledged that the dossier containe d appropriate information on PCR detection 
methods for identification of MS8 and RF3 transgenic lines (Opinion, 19 May 1998). 
368. Barnase and barstar:  The barnase and barsta r genes, derived from the bacterium Bacillus 
amyloliquefaciens, each encode a different small si ngle-chain protein. Both of these proteins have 
been studied extensively as models for protein fold ing because of their small size, and there is an 
abundance of published scientific information relati ng to research work conducted since the early 
1960s. 
369. The barnase gene encodes a ribonuclease that is  naturally secreted by the bacterium. 
Ribonucleases are ubiquitous in nature, and serve many  biological functions. In this case, the secreted 
ribonuclease serves to protect the environment of the b acteria.  Conversely, the barstar gene encodes a 
specific protein inhibitor of this ribonuclease. In th e Bacillus species from which the two proteins are 
derived, the function of the barstar protein is to protect the organism from the otherwise toxic effects 
of its own barnase activity. This naturally occurring system is well studied and the interaction of the two proteins is known to be highly specific. 
370. Under the control of a highly tissue-specific plant promoter from tobacco (PTA29), 
expression of barnase and barstar in the MS8xRF3 hy brids is restricted exclusively to the pollen 
producing cells in developing anthers and only when the plants are flowering. The two proteins are not expressed elsewhere in the plant, including the leaves, stems or seeds. 
371. Gene expression data:  For the parental RF3 line, barstar messenger RNA (mRNA) was 
barely detected in flower buds only, but not in any other plant tissues, including the seeds. As expected, because expression of the ribonuclease resu lts in cell death, barnase mRNA could not be 
detected in any tissues from the MS8 line. 
372. Expression of PAT protein:  The enzyme responsible for herbicide tolerance, PAT, is mainly 
expressed in the green tissues of th e plant. There is some expres sion in other tissues including the 
seeds, but at such low levels that specific en zyme activity was not detectable. Messenger RNA 
(mRNA) corresponding to the bar gene  could be detected at extremely low levels in the leaves and 
flower buds of parental lines MS8 and RF3, but not in the seeds of the plants. 
373. Hybrid MS8xRF3 would be expected to express hi gher levels of PAT than either parental 
line. Data were provided indicating that the levels of PAT expressed in the seeds of the individual parental lines were detectable using the speci fic Enzyme Linked Immunosorbent Assay (ELISA) 
system, with a detection limit of approximately 5 ng/ml. As expected, the level of PAT protein in various oil fractions of seeds derived from the MS 8xRF3 hybrid is below the limit of detection. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-80 
  
  374. Protein detection methodology:  As well as detailed DNA-based detec tion protocols, the 
company provided protein-based detection and identification methodologies (ELISA and test kit) 
which were evaluated at the Sept ember 2001 meeting of the Scientif ic Committee "Transgenic Plants" 
of the Biosafety Council (EC 63-30). In its discuss ions of the information, the Committee raised 
several matters concerning the protocol for detec tion of the PAT protein using ELISA. Concerning 
amounts of PAT protein detected, there were questions  raised on the use of the standard curve and on 
the limit of detection. It was also remarked that the detection methods proposed by the company were 
qualitative rather than quantitative.  
375. However, quantitative immunoassay methods to detect novel proteins in foods derived from 
transgenic crops were under development during th e late 1990's. The two most common tests are 
ELISA and lateral flow strips. Commercial immu noassay methods were reportedly available for 
detection and  quantification of a number of transg enic proteins including the PAT protein in 200059. 
As there are numerous transgenic food crops that ha ve been genetically modified for tolerance to the 
glufosinate-ammonium herbicide, detection of PAT in the MS8xRF3 hybrids is  not an event-specific 
detection method. Information supplied by Strategi c Diagnostics Inc (Delaware, USA) indicates that 
their Lateral Flow test for oilseed rape was commercially available in April 2002. 
376. Conclusion: The available evidence indicat es that immunoassay-based detection methods 
suitable for the detection of PAT protein in MS8xRF3 hybrid transgenic plants were commercially available as early as 2000.  
Question 17 – part 2 : 
 
377. Additional information regarding the provision of  an event-specific quantitative detection tool 
was sought on 25 February 2003 (EC 63-141). The re quest for a detection method that is "event-
specific" directly implies the use of a DNA-based method rather than a protein-based method, which 
can be quantitative but in this case is not event-specific.  
378. The company provided both DNA-based (PCR primers and protocols) and protein-based 
methods (ELISA and test kit) for detection and iden tification of its transgenic lines. This information 
together with reference material was used in an  independent laboratory to evaluate the detection 
protocol. The results of this evaluation indicated  that the DNA-based PCR detection methods were 
reproducible and valid for the transgen ic oilseed rape lines MS8 and RF3.  
379. The provision of event-specific oligonucleotide primers for unambiguous identification of 
transgenic plant lines readily enables use of qualitative PCR methods, but also allows development of quantitative PCR technology according to plant species. Quantitative PCR methods have been 
developed for a range of food commodities including  soybean and maize products but validation of 
these methods is not straightforward. Moreover, it is generally recognised that quantitative protein-
based methods of detection are more directly accessible.  
380. Quantitative detection is an integral part of  enforcement capabilities especially concerning 
labelling regulations. However, it is not a necessary component of a safety assessment. Given the comprehensive nature of the information and ma terial provided in the updated dossier regarding 
identification primers, protocols and plant-deri ved DNA reference material, and the existence of 
                                                      
59 International Life Sciences Institute (ILSI) Euro pe Novel Food Task Force in collaboration with the 
European Commission's Joint Research  Centre (JRC) and ILSI International Food Biotechnology Committee, 
Joint Workshop: Method Development in Relation to Re gulatory Requirements for the Detection of GMOs in 
the Food Chain, December 2000 . Journal of AOAC Internati onal, Vol. 85, No. 3, 2002.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-81 
 
 
  established quantitative protein-based detection methods , I consider that further information relating 
to quantitative event-specific detection tools for tr ansgenic oilseed rape lines MS8 and RF3 is not 
necessary to ensure that conclusions of the safety assessment were valid. 
381. Conclusion:  Additional information regardi ng an event specific, quantitative detection 
method requested in February 2003 is not necessary to ensure that the conclusions of the safety 
assessment are valid. 
Question 18:  Given the information before th e Panel, including the SNIF and the updated 
environmental risk assessment (referenced ab ove), was the information regarding molecular 
data requested by the CA (EC-63/At.144) necessar y to ensure that conclusions of the safety 
assessment were valid? 
Dr. Healy  
382. The original dossier was supplemented with a dditional molecular characterisation data and 
other information to conform with particular requi rements of the Belgian Biosafety Council, the SCP 
and Member States. The totality of the data a nd information provided allowed a comprehensive 
assessment of the safety of food and feed derived from transgenic oilseed rape lines MS8, RF3 and 
hybrids, as well as the potential environmental impact. Previously, both the Biosafety Council and the 
SCP had declared that these lines do not pose human health and safety concerns, and the additional 
information sought between 1998 and 2002, and sub sequently provided by the company, had not 
altered these favourable conclusions.  
383. Additional Information Sought by CA:  The new Belgian guidelines on molecular 
characterisation were developed over a period of time culminating in the final draft version 
(version 6) being distributed for comments to th e Scientific Committee in November 2001. This 
version was submitted to the members of the Biosaf ety Council for final approval at the meeting of 
February 2002 (EC-63/At.105).  Additional informat ion was sought 'in order to bring the molecular 
data in the file into line with the new Belgian guidelines on molecular data: evaluation of the presence and functionality of new chimeric ORFs via bi oinformatics on the sequence of the insert and the 
flanking areas'. 
384. It is noted that more detailed requirements c oncerning molecular characterisation data were 
required by Belgium prior to September 2001. In r esponse, an extended package of information was 
provided by the company, and this additional inform ation was evaluated at tw o subsequent meetings 
of the Scientific Committee "Transgenic Plants " on 27 September 2001 and 7 February 2002. After 
some modifications, the Scientific Committee approved the information supplied in these additional documents. It is also noted however that the new Belgian guidelines were deve loped in parallel with 
the ongoing assessment of the dossier and requests to  the company for further molecular information. 
It is surprising therefore that the informati on necessary to comply with the new molecular 
characterisation guidelines was not requested until July 2003. 
385. Impact of Additional Information on the Safe ty Assessment:  Given the pace of advancing 
knowledge in the field of molecular biology and plant biotechnology and the rapidly evolving technical capabilities, for a foreseeab le time, there will often be a discrepancy between the scientific 
data submitted in a dossier for assessment, and the information possible from the most recently 
developed experimental techniques. In the specifi c case of the frequently updated dossier on MS8, 
RF3 and hybrids, it is clear from the wording of the request to the company that the additional 
information sought is for the purpose of "simply" ma king the file consistent with the current Belgian 
guidelines on molecular data.  This additional inform ation does not add substantially to the weight of WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-82 
  
  evidence that supports the lack of human health an d safety concerns associated with the use of the 
transgenic oilseed rape.  
386. In this constantly changing environment,  the data requirements for the molecular 
characterisation of transgenic crops are not static. In general, there is a recognised need to constantly 
monitor the progress of technical advances and adapt regulatory guidelines accordingly as techniques move from the highly experimental area to more  validated and established methodology. It is 
acknowledged for example that newly evolving research fields such as proteomics and metabolomics may play a strategic role in the future assessment of  food products derived from transgenic organisms.  
387. Conclusion:  The additional information sought by the CA in the email of 14 July 2003 (EC 
63-144) on molecular data was requested to upda te the dossier to new guidelines and was not 
necessary to ensure the conclusions of  the safety assessment were valid.  
Dr. Snape  
388. See answer given to Question 16 
Question 19:  Given the information before the Panel, including the SNIF, the updated environmental risk assessment and the clarific ation provided by the notifier (EC-63/At.147), 
was the information regarding ecological effect s of this product on agricultural systems 
requested by the lead CA (EC-63/At.149) necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Andow  
389. The lead CA requested the following information (EC-63/At.149, 10 October 2003): "The 
Council found a shortcoming highlighted in the report to be sufficiently serious in terms of Annex 2, 
D2 points 4, 5, 7, 8, 9 of Directive 2001/18:  the data on file are not precise enough to inform the Council properly about the impact of commercial crops of Ms8 or Rf3 or their hybrids, in the presence of glufosinate on the parameters set in the aforementioned points in agricultural ecosystems.  
Further data are awaited concerning: farmland dive rsity (macro-fauna, weed flora and microbial soil 
ecosystem), food web integrity (trophic structur e), population dynamics of key species, life-cycles, 
etc." 
390. The lead CA is referring to Directive 2001/18/ EC Annex 2, section D2, which is reproduced 
here:  
D2. In the case of genetically modified higher plants (GMHP);   
4. Potential immediate and/or delayed envi ronmental impact resulting from direct and 
indirect interactions between the GMHP and target organisms, such as predators, parasitoids, and pathogens (if applicable);   
5. Possible immediate and/or delayed environmental impact resulting from direct and indirect interactions of the GMHP with  non-target organisms, (also taking into 
account organisms which interact with ta rget organisms), including impact on 
population levels of competitors, herbivores, symbionts (where applicable), parasites 
and pathogens.;  
7. Possible immediate and/or delayed effects on animal health and consequences for the feed/food chain resulting from consumption of the GMO and any products derived from it if it is intended to be used as animal feed;   WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-83 
 
 
                                                       8. Possible immediate and/or delayed effects on biogeochemical processes resulting 
from potential direct and indirect interacti ons of the GMO and target and non-target 
organisms in the vicinity of the GMO release(s);   
9. Possible immediate and/or delayed, direct and indirect environmental impacts of the specific cultivation, management and harvesting techniques used for the GMHP 
where these are different from those used for non-GMHPs.  
391. The notifier's original response to these A nnex 2 guidelines is given in EC-63/At.112, 
14 January 2003. 
392. The notifier's full response to point 460 was "This is not applicable to glufosinate tolerant 
oilseed rape."  This is an insuffi cient response.  At a minimum there should be an argument as to why 
the point is not applicable.  I conclude that the re quest by the lead CA for more information on point 4 
was necessary to ensure that conclusions of the safety assessment were valid. 
393. The notifier's response to point 5 covers 4 pages.61  The notifier concludes  
– Scientific experts confirm that the hor izontal gene transfer from the GMHP to 
bacteria is extremely unlikely although theoretically it cannot be totally excluded.  In the very unlikely case wher e such a transfer would occur this 
would have no impact since the transgenes involved would not provide a selective advantage. 
– Scientific experts also confirm that the GM OSR has no effect on honeybees 
and epigaeic predatory arthropods of oilseed rape. 
– There are no identified potential effe ct of the GMHP on birds and small 
mammals. 
394. I believe that the notifier's first conclusion is well supported by the data and arguments they 
muster.  I believe that the data on epigeal predator s is weak, but even with additional data, I am not 
convinced that a major adverse effect will be identi fied.  The data on birds and rabbits are also weak, 
but again, I am not convinced that additional data will reveal a major adverse effect.   
395. As there are literally hundreds of species of non- target organisms that could be tested, it can 
always be argued that more species should be evaluated.  Indeed, several important ecological functional groups were not evaluated, including parasitoids and detritivores.  Without a specific 
reason, it is difficult to argue that testing a paras itoid is necessary for the risk assessment.  A case 
could be made that a detritivore would have been a better choice for study than epigeal predators.  
However, if this was the specific concern of the lead  CA, it would have been appropriate to clarify the 
point.  Hence, I conclude that the request by the lead CA for more information on point 5 was not necessary to ensure that conclusions of the safety assessment were valid. 
396. The notifier's response to point 7 covers 3 pages.62  The notifier argues that there is no reason 
to believe that the feed value of GMHT oilseed ra pe will be different from conventional oilseed rape, 
provides a summary of data on the major nutrients of seed and meal, and report the results on a rabbit and chicken feeding study.  It is possible that the compositional studies are not adequate or the wrong 
 
60 EC-63/At.112, p. 28, 14 January 2003. 
61 EC-63/At.112, pp. 29-32, 14 January 2003. 
62 EC-63/At.112, pp. 37-39, 14 January 2003. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-84 
  
  species have been used for feeding studies.  I am unable to conclude that the request by the lead CA 
for more information on point 7 was necessary or not necessary to ensure that conclusions of the 
safety assessment were valid. 
397. The notifier's response to point 8 is one page.63  The notifier claims that oilseed rape does 
participate in biogeochemical cycles, therefore there are no expected effects on biogeochemical cycling.  The notifier further supports this view by  reporting that there have been no observed effects 
on rhizoshere bacteria and no observed effects on the plants growing in the field the year following a 
crop of GMHT oilseed rape. 
398. The notifier is mistaken to claim that oilseed rape does not participate in any biogeochemical 
cycles.  The root and leaf litter participate in carbon cycles, and it may have subtle effects on phosphorous cycles, as it will reduce proliferation of my corrhizal fungi relative to most other plants.  
It is likely that participation in carbon cyclin g is one of the main ways it participates in 
biogeochemical cycles.  A simple litter degradation st udy would determine if it is likely to have any 
effects on carbon cycling.  Hence, I conclude that the request by the lead CA for more information on point 8 was necessary to ensure that conclu sions of the safety assessment were valid. 
399. The notifier's response to point 9 covers two pages.64  The notifier argues  
The only change in cultivation techniques used on the herbicide tolerant (hybrid) 
oilseed rape is the possibility to use glusof inate ammonium as selective herbicide.  
However, glusofinate-containing herbicide can be used on the crop only if they are 
registered for this specific use in the different Member States according to Directive 
91/414/EEC.  The safety assessment and the assessment of the impact of the herbicide use on the environment are done in the said 91/414 application. 
400. The notifier argues that except for herbicide use, other cultivation practices are unlikely to 
change.  This contrasts sharply with claims by others that GMHT crops are likely to result in changes 
in tillage practice.  The notifier does not address th is possibility in detail a nd states only that soil 
preparation practices will be identical.  This seem s to be an insufficient argument.  In addition, 
although the UK-FSE trails will not be published until later in 2003, everyone involved was aware of 
the experiments and the possibility that the associated herbicide use would have adverse 
environmental effects.  These issues are not addr essed in the response of the notifier.  Hence, I 
conclude that the request by the lead CA for more  information on point 9 was necessary to ensure that 
conclusions of the safety assessment were valid. 
401. The lead CA requested information on 10 October 2003.  The notifier submitted the material 
to be reviewed on 14 January 2003.  The 269 days th at elapsed seem excessively long to complete the 
review and articulate the questions. 
Dr. Snow  
402. The vagueness of this request and the lack of related information from the notifier make it 
difficult to provide a clear answer to this question from the Panel.  
403. The lead CA asked for inform ation about effects on "farmland diversity (macro-fauna, weed 
flora and microbial soil ecosystem), food web inte grity (trophic structure), population dynamics of 
key species, life-cycles, etc." (EC-63/At. 149 translation).  Although this request seems to ask for 
                                                      
63 EC-63/At.112, p. 40, 14 January 2003. 
64 EC-63/At.112, pp. 41-42, 14 January 2003.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-85 
 
 
  some unnecessary data (and the request is quite vague), several Member States were concerned about 
the ecological effects of more intensive herbicide use.  I assume that th is is the focus of concern – that 
more information was requested to determine the e ffects of cultivating new herbicide-tolerant crops 
on the weed plants that support insect and animal popul ations in farmland habitats in these countries.    
404. Realistically, this is a difficult set of questions  to answer, regardless of whether one uses basic 
theory or empirical research.  As noted above, the indirect effects of introducing herbicide-tolerant 
crops to countries like the UK are still being investigat ed, so in this sense th e requested information 
could be considered as necessary.  However, it not feasible to obtain scientific data on all of the 
processes listed by the CA without extensive multi-year studies.  Even the Farm Scale Evaluations are 
too short and too small-scale to answer these questions (e.g., Andow 2003, Squire et al. 2003).  Adverse effects on flora and fauna are mentioned in SPS and ISPM 11, but it is not possible to test for 
all of these effects prior to deregulation.  Inst ead, scientific committees typically use their best 
judgement to recommend approving or denying applications for marketing.   
Dr. Squire  
405. The updated environmental risk assessment is comprehensive on topics for which data are 
available. The further information on ecological ef fects requested by the lead CA was clearly not 
available, and could only be in existence if there had been either large scale experimental 
measurements on the habitats typical of where th e crop would be grown commercially or specially 
commissioned experiments on trial crops, as in the UK's Farm Scale Evaluations. Since cropping with 
this variety and its herbicide has potentially new eff ects on the arable flora (i.e. different from those of 
other oilseed rape varieties with other herbicides) , which may be severely depleted in any case, it is 
legitimate to ask what such effects might be. However, the general matter of the need for a comparator is relevant here (Notes, paragraphs 
32-35). Surely it is incumbent on both sides in the 
argument to proffer their standard or comparator against which the new technology should be judged. 
Question 20:  Are the conclusions and recommendati ons in the Report of the Group of Experts 
Mandated by the Belgian Biosafety Advisory Council (EC-63/At.167 pp.20-21) regarding the agricultural guidelines proposed by the applicant consistent with the Belgian Biosafety Advisory 
Council's conclusion that the agricultural guidelines are "impracticable, hardly workable and hard to control"? 
Dr. Andow  
406. The Belgian Biosafety Council concluded (EC-63/At.166, 27 January 2004) as follows 
Concerning the environemental risk, the Biosafety Advisory Council is of the opinion that some risks associated with these GM crops will be reduced provided that the 
following conditions are strictly applied: 
– The agricultural guidelines must be (1) adapted to the recommendations of 
the experts and to the recommendations made by the Member States due to differences in agricultural practices a nd landscapes, (2) applied by all the 
operators supported by appropriate legislation and control, and (3) 
continuously updated according to the ne w available scientific information. 
– The post-market monitoring plan must (1) assess compliance with the 
agricultural guidelines, (2) assess and determine the effectiveness of the 
proposed risk management strategies of  the agricultural guidelines in limiting WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  gene flow and its potential conse quences and in preserving farmland 
biodiversity, (3) be adapted to the recommendations made by the Member 
States of the European Union due to di fferences in agricultural practices and 
landscape, (4) be continuously upda ted according to the new available 
scientific information and (5) the no tifier must provide a more detailed 
description of the tasks and the kind of data that will be collected by different 
networks involved in the general su rveillance.  In this context the 
detection/identification method must be validated. 
Furthermore, the Biosafety Advisory Council considers that presently, a number of recommendations of the agricultural guide lines are impracticable, hardly workable 
and hard to control in current agricultura l practices, hence vertical gene flow and 
negative consequences on biodivers ity may not be controlled. 
407. The expert recommendations referred to are (EC-63/At.167, 3 February 2004, pp. 20-21) 
408. 4.2.3.  Agricultural guidelines  
Taking the importance of the agricultural guidelines into account, the Group of Experts recommends that the agricultural guidelines should be translated in the national or local language(s) of each MS  of the EU.  The guidelines should be 
readable and understandable by all the opera tors (e.g. farmers, seed suppliers) that 
will handle the seed, crop and product of MS8, RF3 and MS8xRF3.  A widely 
comprehensible language should be used.  Moreover, the agricultural guidelines 
should be adapted to the recommendations  made by the Member States of the 
European Union because of differences in agricultural practices and landscape and be 
continuously updated according to the ne w available scientific information. 
Given that the occurrence of spontaneous inter-specific crossings among oilseed rape, 
Brassica rapa and Brassica juncea crops has already been reported, the Group of Experts recommends that each farmer growing B. napus, B. juncea or B. rapa crops in the neighbourhood of the transgenic oilseed rape fields is aware of the agricultural 
guidelines. 
Considering that seeds will be imported and transported and that seed spillage might occur, feral oilseed rape plants might estab lish and persist outside the fields (e.g. on 
roadsides, railways, wastelands, points of import).  For this reason, the Group of Experts recommends that every operator should be informed on the appropriate management measures to be taken in the case of accidental seed spillage and the establishment of feral oilseed rape populations.  It should also be made clear to whom 
these events must be reported.  Where seed  spillage occurs, the agricultural guidelines 
should recommend that the seeds must be swep t or shovelled into sealed containers.  
In addition, seed spills should be recorded and monitored in subsequent years in order to allow appropriate control. 
To limit seed spillage during transport and the potential establishment of feral herbicide-tolerant oilseed rape popula tion, the agricultural guidelines should 
recommend transporting the seeds in closed and sealed containers.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-87 
 
 
  To limit the development of multiple herbicid e-tolerant plants through vertical gene 
transfer of the herbicide-tolerant trait,  the agricultural guidelines should recommend 
that: 
– the cultivation of transgenic oilseed rape  with tolerance to other herbicides in 
the same or nearby rotation must be avoided, 
– oilseed rape must not be grown on the same land more than one year in four. 
– Given that reliance on a single mode of herbicide control exerts a high 
selective pressure on the weed population and volunteers, which may lead to 
the development of resistance to the concerned herbicide and that rotating 
active ingredients reduces resistance de velopment, the agricultural guidelines 
should recommend that: 
– the glufosinate ammonium must be used  in combination with other herbicides 
during the same rotation cycle, 
– the use of different crops tolerant to glufosinate ammonium must be avoided 
in the same rotation cycle, 
– integrated weed management systems should be applied. 
Given that agricultural weeds become l ess abundant in fields where glufosinate 
ammonium is applied and that the environm ental disbenefits of very clean fields 
might be judged unacceptable, uncropped fields and/or field margins and untreated 
field margin strips might be the only physi cal habitats to preserve these plants and the 
whole chain of living organisms living on and from these plants.  Within those fields, 
margins or strips, the agricultural weeds and the accompanying fauna may find a place to survive, provided that the farm ers allow them to.  For this reason the 
agricultural guidelines should  recommend farmers to preserve field margins (hedges, 
hedgerows, grassy borders, small woodlots and others), leave field margins unsprayed 
and limit herbicide drift.  The agricultural guidelines should also recommend farmers to use band spraying if the negative impact of cleanliness is to be reduced. 
To limit any selective pressure of the glufosinate ammonium on plants outside the field (e.g. herbicide-tolerant feral oilseed ra pe plants, wild relatives in field margins), 
the agricultural guidelines should recommend farmers to avoid herbicide drift in field 
margins according to the current principles of good agricultural practices. 
409. The original proposed Agricultural Guidelines are in EC-63/At.123, 14 January 2003. I 
consider the question from the Panel to be ambi guous.  The conclusions and recommendations in the 
Report of the Group of Experts (RGE) are about improving the original Agricultural Guidelines 
(OAG) proposed by the notifier.  The conclusion by  the Belgian Biosafety Advisory Council (BBAC) 
is also about the original Agricultural Guidelines.  The stated question may be interpreted to be: do 
the conclusions and recommendations in the RGE support the conclusion by the BBAC that the OAG 
are "impracticable, hardly workable and hard to control"?  Alternatively, the stated question may interpreted to be: is there anything in the conclu sions and recommendations in the RGE that contradict 
the conclusion by the BBCA that the OAG are "impracti cable, hardly workable and hard to control"?  
I will assume that the stated question is not anythi ng similar to: Are the OAG "impracticable, hardly WT/DS291/R/Add.6 
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  workable and hard to control," or are any of  the conclusions or recommendations in the RGE 
"impracticable, hardly workable and hard to control"?  I will address the first possible alternative here. 
410. First, it should be clear that the RGE does not contain any conclusion similar to that of the 
BBAC, i.e., that the OAG are "impracticable, hardly workable and hard to control." 
411. The RGE states 
To allow safe and sound integration of MS8, RF3 and MS8xRF3 oilseed rape in 
Europe the notifier proposed agricultural guidelines giving guidance to farmers and 
seed suppliers.  Since the experts considered  that the guidelines would be crucial in 
limiting vertical gene flow and its potential consequences, it was strongly recommended that the practical mitigation measures as described in the guidelines 
would be followed. 
412. This implies that some of the mitigation measur es in the OAG are consider impracticable, as 
there would be no need to specify "practical m itigation measures" in the statement if all were 
considered practical. 
413. The RGE also states 
Moreover, it was proposed that the effectiv eness of the proposed risk management 
strategies in limiting vertical gene flow  (and its potential consequences) and in 
preserving farmland biodiversity should be assessed in the post-market monitoring plan.  In addition, an independent farmers' audit to monitor compliance with the 
agricultural guidelines should be  foreseen on a regular basis. 
414. This is an critically important control point th at was lacking in the OAG.  This implies that 
the RGE considers some of the risk management me asures proposed in the OAG to be hard to control. 
415. The RGE organizes the recommendations for th e Agricultural Guidelines along routes of 
escape and potential adverse effects.  The OAG is organized around farm operations.  The OAG emphasizes workability for farmers and seed distri butors, while the RGE emphasizes workability for 
attaining the risk management objectives.  Obviously , both must be met ultimately, but it is not clear 
from the BBAC conclusion what kind of workability is considered. 
416. Thus the RGE supports the BBAC conclusion that the OAG are impracticable and hard to 
control.  It is not clear if the RGE supports th e BBAC conclusion that the OAG are hardly workable. 
417. In passing, and not really on the point, I ag ree with the BBAC that parts of the OAG are 
"impracticable, hardly workable and hard to cont rol," but would prefer to consider these parts as 
needing considerable improvement before they ar e acceptable.  I also consider some of the 
recommendations in the RGE to be "impracticable, ha rdly workable and hard to control," and overall 
the Agricultural Guidelines will need  additional work so that they  accomplish the risk management 
goals. 
Dr. Squire  
418. The question is whether the words "impracticable, hardly workable and hard to control" used 
by the Belgian Biosafety Advisory Council are justified on the basis of the report by its Group of 
Experts. The Group of Experts does not use this wo rding as such but makes ca utionary remarks that  WT/DS291/R/Add.6 
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  the guidelines are not sufficient as they stand and shou ld be extended and that there could be practical 
problems in successfully implementing them. Examples include –  
• "each farmer growing B. napus , B. rapa and B. juncea , in the neighbourhood of the 
transgenic oilseed rape field is aware of the agricultural guidelines": this requires that 
non-GM farmers need to make themselves aw are of GM issues, and that all farmers 
will be cooperative neighbours.  
• "every operator should be informed on the appropriate management measures to be 
taken in the case of accidental seed spillage  …etc.": this in reality is probably 
unworkable, since many spillage events w ill go unnoticed, and there are such a large 
number of feral populations arising from such events. 
• "seed should be swept or shovelled into sealed  containers" and "(spillage sites) should 
be recorded and monitored in subsequent years": these are likely to be impracticable 
in commercial agricultural areas; the measu res would place an intolerable burden on 
whoever was considered responsible if that could be decided (the grower, the 
transported, the buyer, the roads authority?). 
419. Several other of the Group of Experts' recommendations are workable, but the above three 
examples would appear to justify the Belgian Safety Advisory Council's choice of words.  
Trifolium/Monsanto/Danisco Roundup Ready fodder beet (A5/15)  
C/DK/97/01  (EC chronology 64) 
 
Question 21:  Given the information before the Pa nel, including the lead CA's positive opinion 
(EC 64/At. 29-30) and the conclusions of the EC SCP (EC-64/At.83), did the additional risk assessment provided by the notifier (EC-64/At.104-105) in response to requests by the Dutch CA for a theoretical safety assessment address outstanding scientific concerns related to the potential risks associated with this product? 
Dr. Nutti  
420. Based on the information provided by the applican t in EC-067/At.1 and the analysis done by 
the EC SCP (CDA-35A) and following the Codex Guid elines, my understanding is that the additional 
risk assessment provided by the notifier was not necessary in the first place. It does not address outstanding scientific concern since they are not re lated to the potential risks associated with this 
product.  
421. It is important to point out that both the EC  SCP and the Danish CA overall assessments have 
stated that there is no evidence indicating that the use of the fodder beet tolerant to glyphosate with the purpose to be used as any other fodder beet is likely to cause any adverse effects on human health 
and the environment. 
Dr. Andow  
422. The issue addressed in EC-64/At.104-105, 19 October 1999, was the existence and sequence 
of backbone DNA.  This issue had not been addressed previous to this date for this transgenic fodder 
beet.  The notifier indicated that they would pr ovide information documenting that the backbone DNA 
was absent, but in the meantime would provide a risk assessment assuming the entire backbone DNA 
was present (EC-64/105, 19 October 1999).  This risk assessment was not available in any of the 
materials before the Panel. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  423. The issue addresses the possible activity of back bone DNA in the plant.  If it exists and it 
becomes active, it could result in unanticipated phenotypes that could lead to adverse effects on 
human health or the environment. 
424. Thus I conclude that the additional risk assessment would have addressed an outstanding 
scientific concern related to the potential risks associated with this product. 
425. The request by the Dutch CA was on 4 August 1999, following the launching of the Inter-
Service Consultation on 4 September 1998.  The notifier provided additional information on 24 September 1998, 25 September 1998, 5 Octobe r 1998, 13 November 1998 and 5 March 1999.  
Counting from the date of the launching of the In ter-Service Consultation, the Dutch CA took 334 
days.  Counting from the date the notifier last pr ovided additional information, the Dutch CA took 
152 days.  In either case, the number of days  seems like a long time to make the response. 
Question 22:  Given the information before the Pa nel, including the conclusions of the SCP's 
risk assessment, was the inform ation requested by the Italian CA in March 2000 (EC-64/At.116) 
necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
426. Based on the information provided by the applican t in EC-067/At.1 and the analysis done by 
the EC SCP (CDA-35A), I understand that there was no need, as far as food safety is concerned, for the request made by the Italian CA (EC-64/At.116) in  order to ensure that conclusions of the safety 
assessment were valid. 
Dr. Andow  
427. The information requested by the Italian CA (EC-64/At.116, 14 March 2000) is as follows. 
Referring to the conclusion of the last meeting of the Regulatory Committee under Directive 90/220/EEC, Italy would be very pleased to receive from the notifier more information concerning the transfer and the recombination of genes in natural 
conditions, on the efficacy of the use of the Roundup herbicide and on the evaluation 
of the possible crossing with spontaneous species. 
428. Issues related to the transfer and recombinati on of genes in natural conditions and to the 
evaluation of possible crossing with spontaneous (w ild?) species were addressed in the SCP Opinion 
(EC-64/At.83, 23 June 1998) and were a ddressed in the original notification. 
429. It is possible that the Italian CA believed these assessments to be inadequate.  If so, the CA 
should have indicated this in the question.  However, as discussed below, this is unlikely. 
430. Issues related to the efficacy of the use of glyphosate were not addressed in the SCP Opinion, 
but I fail to understand how such issues relate to a risk assessment, and the Italian CA provides no 
guidance.  This question was NOT necessary to ensu re that conclusions of the safety assessment were 
valid.   
431. In the response to the Italian CA (EC-64/At.119,  12 July 2000), the notifier states that there 
are no new data in the document, only clarifications.  Given that the Italian CA did not follow up on 
this response, I must assume that the response satisfied the Italian CA's concerns.    WT/DS291/R/Add.6 
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  432. Thus, the issues raised by the Italian CA had been addressed in previous documents.  Based 
on the detailed responses from the notifier in EC- 64/At.119a, the question on possible crossing with 
spontaneous species was NOT necessary, but the ques tion on transfer and recombination in natural 
conditions was necessary to ensure that conclusions of the safety assessment were valid.   
Question 23:  Given the information before the Panel, including the conclusions of the lead CA's 
positive opinion (EC-64/At.29-30) and EC SCP op inion, did the additional information provided 
by the notifier in response to requests by the Du tch CA and by the UK for additional data 
regarding molecular characterization address outstanding scientific concerns related to 
potential risks associated with this produc t (EC-64/At.113 and 119)?  Was the molecular 
characterization provided by the applicant suffi cient to enable the Dutch CA and the SCP to 
conduct a risk assessment and to support the conc lusions reached regarding the safety of the 
product? 
Dr. Andow  
433. The issue addressed in EC-64/At.104-105, 19 October 1999, was the existence and sequence 
of backbone DNA.  This issue had not been addressed previously for this transgenic fodder beet.  The 
notifier indicated that they would provide in formation documenting that the backbone DNA was 
absent, but in the meantime would provide a risk assessment assuming the entire backbone DNA was 
present (EC-64/105, 19 October 1999).  This risk assess ment was not available in any of the materials 
before the Panel.  The notifier provided the Dutch CA with the molecular evidence in EC-64/At.113, 
23 February 2000. 
434. This issue addresses the possible activity of backbo ne DNA in the plant.  If it exists and it 
becomes active, it could result in unanticipated phenotypes that could lead to adverse effects on 
human health or the environment. 
435. Thus I conclude that the additional informa tion addressed an outstanding scientific concern 
related to the potential risks associated with this product. 
436. The UK CA also addressed the same issue to th e notifier, apparently unaware that the issue 
had been raised by the Dutch CA and addressed alrea dy by the notifier.  The notifier clarified this in 
EC-64/At.119, 12 July 2000. 
437. The molecular data was included with a summary and transmittal letter from the notifier on 
23 February 2000.  I will not comment on the sufficiency of these data. 
Monsanto Roundup Ready cotton (RRC1445)  
C/ES/97/01  (EC chronology 66) 
 
Question 24:  Does the information before th e Panel, including the full application 
(EC-66/At.3-12) and the EC 's SCP opinion (EC-66/At.43), provide scientific support for  the 
objections raised by EC member States (EC-66/At.57) concerning the adequacy of the 
monitoring plan, the antibiotic resistance marker genes, and herbicide residues? 
(a) What criteria can be used to judge if the final monitoring plan submitted by Monsanto in January 2003 was complete? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  Dr. Andow  
Scientific support for objections:  
438. This response addresses only issues related to the adequacy of the monitoring plan, and does 
not address issues related to antibiotic resist ance marker genes and herbicide residues. 
439. The lead CA reached the following conclusions  (EC-66/At.05, Submission of lead CA to 
COM, 19 Nov 1997, Overall Assessment).   
2. From the risk assessment it is conc luded that there is no reason to suppose 
that the harvest and handling of RRC Line 1445 tolerant to glyphosate herbicide, 
have adverse effects on the environment and human health. 
9. The dossier was considered by Nationa l Commission on Biosafety.  The main 
aspects considered in the risk assessment were: 
– Capacity to survive, establish and disseminate. 
– Potential for gene transfer. 
– Products of expression of inserted sequences. 
– Phenotypic and genetic stability. 
– Pathogenicity to other organisms. 
– Potential for adverse effects to humans. 
10. The National Commission on Biosafety considers that, for the considered 
uses, there is no significant difference as fa r as environmental and human health risks 
related to other cotton. 
16. Finally, as far as potential effects for non-target organisms is concerned, CP4 EPSPS protein is broadly present in nature.  Therefore organisms which feed with 
plants and microorganisms are exposed to this protein.  Studies with birds feeded with RRC line 1445 cottonseed meal have been conducted and no significative 
difference of this feeding was detected.  Moreover, EPSPS protein exist in nature and 
is considered non-toxic to animal species.  On the other hand, cotton is a unique crop 
that mammals and other species which cons ume vegetation avoid feeding on the plant 
due to both gossypol in the plant and the morphology of the plant. 
440. These excerpts show that the risk assessment da ted 19 November 1997 by the NCB did not 
consider indirect effects on non-target organisms, long-term or spatial scale effects on non-target species, effects associated with cha nges in the cropping system or th e evolution of resistance in weeds 
to glyphosate.  The NCB does consider whethe r there are any significant differences between 
anticipated risks from RRC 1445 compared to conven tional cotton.  Although the NCB concludes that 
there are no significant differences (point 10), they do not provide a scientific argument that this 
conclusion extends to the potential effects not cons idered in the risk assessment.  Because the NCB 
considered that the risks they assessed were inc onsequential, the NCB did not propose any monitoring 
plan.  WT/DS291/R/Add.6 
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  441. The SCP provided the following Opinion (EC-66/At.43, 14 July 1998.  Opinion of the 
Scientific Committee on Plants). 
6.3.3. Safety to non-target organisms:  Exposure of non-target species to seeds can 
be considered very low, due to the morphology of the boll.  Feeding studies with 
birds (seeds) and mammals (both proteins) indicate very low toxicity of the proteins which also occur ubiquitously in the environment in plants and microorganisms.  Field studies on agronomic performance showed equivalent susceptibility of line RRC 1445 and non-modified varieties to diseases and insect pests. 
6.3.4. Resistance and tolerance issues:  Any selective advantage of cotton line RRC 
1445 is restricted to cases where no herbicide other than glyphosate is used on early stages of cotton.  Under normal applicati on rates, the introduced glyphosate-tolerance 
is effective up to the 4-leaf stage only.  Other herbicide, cultivation of rotational crops or winter conditions will kill both modified and non-modified plants.  Volunteers 
should be dealt with by standard agricultural practice except that glyphosate should 
not be used. 
442. These excerpts show that they did not consider indirect effects on non-target organisms, long-
term or spatial scale effects on non-target species, effects associated with changes in the cropping 
system or the evolution of resistance in weeds to  glyphosate.  Because the SCP considered that the 
risks they assessed were inconsequential, the SCP did not propose any monitoring plan. 
443. Sweden commented as follows (EC-66/At.57, 26 April 1999.  Consultation of the Committee 
by Written Procedure).   
Sweden has, in different EU contexts and in earlier statements, put forward the view that herbicide tolerant crops should not be placed on the market until the long-term effects of herbicide tolerant crops on the environment have been better analysed.  
Common principles for evaluation and monitoring of the risks connected to the 
cultivation of herbicide tolerant  crops should be established. 
444. Sweden suggests that long-term effects shoul d be studied prior to marketing and that 
principles for monitoring risks related to the cu ltivation of herbicide tolerant crops should be 
established.  Sweden is saying that effects associ ated with changes in the cropping system should be 
considered both in the assessment and monitoring of  risk.  The scientific literature at that time 
indicated that long-term effects frequently elude de tection when assessed on short time scales, so one 
of the only reasonable ways to address these kinds of effects is via monitoring.  It does not seem appropriate to require long-term experiments for risk assessment because that could delay the process 
by a decade, so monitoring is a possible alternative. 
445. The United Kingdon commented as follows (EC-66/At.57, 26 April 1999.  Consultation of 
the Committee by Written Procedure).  
We would also like to draw to the attenti on of other Member states where GM cotton 
might be widely grown, that this cott on line may have a negative impact on 
biodiversity arising from changes in the way the herbicide tolerant crop is managed. 
446. The United Kingdom is drawing attention to spa tial scale effects and effects associated with 
changes in the cropping system.  The scientific literatu re at that time indicated that large-scale effects WT/DS291/R/Add.6 
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                                                       frequently elude detection when assessed at smaller spatial scales.  One of the reasonable ways to 
address these kinds of effects is via monitoring. 
447. The information in the full application (EC-66/At.3-12) and the EC's SCP opinion 
(EC-66/At.43) do not provide scientific support for the objections raised by EC member States (EC-66/At.57) concerning the adequacy of the mon itoring plan.  This is because the scientific 
information in the full application and the EC-SCP  opinion do not address the scientific basis for the 
objections raised by the EC member states con cerning the adequacy of the monitoring plan. 
448. The objections of the member States (EC-66/ At.57) concerning the adequacy of the 
monitoring plan raise new scientific issues that we re not assessed in the full application (EC-66/At.3-
12) or the EC's SCP opinion (EC-66/At.43).  There is  no monitoring plan proposed in either the full 
application (EC-66/At.3-12) or the EC's SCP opi nion (EC-66/At.43), so the EC member States' 
objections can only be interpreted that a monitoring plan may be or is necessary. 
449. The objections of the member States (EC-66/At.57) concerning the adequacy of the 
monitoring plan are scientifically justifiable.   The EC member States raise specific scientific issues 
that can be addressed in a monitoring plan.  Howeve r, the necessity of a monitoring plan cannot be 
determined from these objections.   
450. It should also be noted that the objections of  the member States (EC-66/At.57) concerning the 
adequacy of the monitoring plan are not all clearly  stated as monitoring issues, and the objections do 
not provide clear guidance to an applicant for how to fully respond.   
451. Excerpt from EC-66/At.64.  Letter from Span ish CA to Monsanto requesting additional 
information regarding the monitoring plan, 1 January 2003. 
Plan de seguimiento 
Se deberán concreter y desarrollar aquello s aspectos susceptibles de ser sometidos a 
una vigilancia general, indicando las posibles actuaciones en cada caso. 
En este sentido, el Plan de seguimiento deberá contemplar, en su caso, el uso del herbicida Glifosato y sus potenciales efect os a largo plazo (incidencia de malas 
hierbas, resistencias, etc), así como cualquier otro efecto relacionado con cambios en las prácticas agrícolas convencionales. 
452. I believe the Spanish CA is requesting that the monitoring plan address potential effects of 
large spatial scale (for example, weed incidence, resi stance) and in relation to changes in agricultural 
practice.  These echo the comment of the UK (EC-66/At.57) and some of the comment of Sweden (EC-66/At.57). 
453. The UK Farm Scale Evaluations (FSE)65 of GMHT crops published in 2003 indicate that one 
anticipated effect of GMHT crops is an alterati on in weed populations and communities compared to 
conventional production.  The precise alteration probably depends on the herbicides used on the 
 
65 Andow 2003, Nature Biotechnology, 21, 1453-1454.  Brooks et al. 2003, Phil. Trans. R. Soc. Lond. 
B, 358, 1847-1862.  Champion et al. 2003, Phil. Trans. R. Soc. Lond.  B, 358, 1801-1818.  Firbank 2003, Phil. 
Trans. R. Soc. Lond. B, 358, 1777-1778.  Haughton et al. 2003, Phil. Trans. R. Soc. Lond. B, 358, 1863-1877.  
Hawes et al. 2003, Phil. Trans. R. Soc. Lond. B, 1899-19 13.  Heard et al. 2003, Phil.  Trans. R. Soc. Lond. B, 
358, 1819-1832.  Heard et al. 2003, Trans. R. Soc. Lond . B, 358, 1833-1846.  Roy et al. 2003, Phil. Trans. R. 
Soc. Lond. B, 358, 1879-1898.  Squire et al. 20 03, Phil. Trans. R. Soc. Lond. B, 358, 1779-1799.  WT/DS291/R/Add.6 
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  GMHT crop and the conventional crop.  Nearly a ll other adverse effects on non-target species would 
likely follow from these changes in weed populations and communities.  Changes to weed populations 
and communities have not been reported in GMHT cotton on a scale similar to the UK-FSE trials.  
These studies follow on a concern published in 2000 that GMHT crops could adversely affect 
skylarks in the UK.66  Although none of these studies existed at the time of the decisions by the NCB 
or the SCP, they partially validate some of the hypothetical concerns expressed by the various 
countries, especially related to spatial and temporal scale. 
454. Considerable theory and evidence indicates that another anticipated effect of GMHT crops is 
the development of resistance to glyphosate in some weed populations.67  Resistance to glyphosate in 
a species of morning glory, which is a weed found in GMHT cotton in southeastern US, has been recently reported.
68  However concerns about resistance have  been widely recognized for some time 
before 1998. 
455. Potential long-term effects of GMHT cotton have not yet been identified and verified 
scientifically. 
456. The Member States submitted questions to the notifier on 22 February 1999.  The notifier 
submitted materials to the SCP on 6 July 1998.  The SCP returned an Opinion on 14 July 1998.  The 
notifier submitted additional information that was circ ulated on 20 November 1998.  After this follow 
3 decisions to postpone the decision-making pro cess.  Depending on which dates are used, the 
Member States used either 94 or 231 days to respond  to the most recent submission by the notifier.  
The shorter time frame is reasonable, especially as it spans the winter holiday season when most 
offices are closed for long periods of time.  The longer period of time seems excessive to formulate and provide the responses to the notifier. 
Criteria to judge monitoring plan:  
457. The specific purpose of monitoring  should be clearly stated.   This purpose should be linked to 
the management of some risk.  This linkage ties monitoring to risk management, and delimits the 
monitoring endpoint.  Although Annex VII.A of Directive 2001/18/EC provides a statement about the objective of a monitoring plan, this statement is not specific enough as the purpose of any particular monitoring plan.  The plan should be more closely linked to actual potential risks, as indicated in Annex VII.C.1-2 of Directive 2001/18/EC. 
458. For example, there are several possible pur poses for monitoring herbicide resistance69 in 
weeds, including: 
                                                      
66 Watkinson et al. 2000, Science, 289, 1554-1557. 
67 See www.weedscience.org , which lists all occurrences of weeds resistant to a herbicide worldwide, 
including cases of resistance to glyphosate. 
68 Baucom and Mauricio 2004, PNAS 101: 13386-13390. 
69 Here I will not distinguish between resistance and to lerance, and will refer to  both as "resistance."  
Baucom and Mauricio (2004, PNAS 101: 13386-13390) distinguish tolerance from resistance, basing the 
distinction on Painter's (1958, Annu. Rev. Entomol. 3: 2 67-290) framework.  They defi ne tolerance as a trait to 
compensate from herbicide damage and resistance as a tra it that prevents herbicide damage.  Painter, however, 
considered both of these to be a part of the concept of resistance, and sugge sted that resistance is divided into 
"tolerance", "antibiosis" and "nonprefe rence."  Antibiosis and nonpreference correspond to the narrow definition 
of "resistance" advanced by Baucom and Mauricio.  I adopt the broader definition of resistance stemming from 
Painter's work. WT/DS291/R/Add.6 
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                                                       • Purpose R1.  Document/Measure the occurren ce of herbicide-resistant weeds.  This 
would provide information prior to any control failures that could be used to alter the 
use of the herbicide or herbicide-tolerant70 crop to delay or a void higher levels of 
resistance in the weed.  Because this o ccurs before any control failures, it would 
provide time to develop a reasoned response to the threat.  This would be particularly 
advantageous to prolong the useful life of the herbicide in question, especially if it had replaced herbicides that caused greater damage to the environment. 
• Purpose R2.  Document/Measure the occurre nce of a weed problem that cannot be 
controlled by the herbicide.  This could provide information of localized control 
failures that could be used to alter the use of the herbicide or herbicide-tolerant crop 
to delay or avoid higher levels of resist ance in the weed.  Because some control 
failures will have occurred, it may be n ecessary to mobilize a rapid response to 
prolong the useful life of the herbicide. 
• Purpose R3.  Document/Measure  the widespread occurrence of a weed problem that 
cannot be controlled by the herbicide.  This  would provide information of widespread 
occurrence of the risk, and would be an indi cation that the risk management practices 
had failed.  One crucial use of monitoring is  to determine when a predefined point of 
failure is reached. 
459. Similarly there are several possible purposes for monitoring changes in weed populations and 
communities, including:   
• Purpose W1.  In the UK, there has been a concern that GMHT crops would adversely effect the skylark, a desirable species.
71  Skylarks feed on weed seeds, so monitoring 
of weed populations and communities could be aimed to monitor the abundance of food for skylarks.  This approach could be extended for any other non-target species of concern. 
• Purpose W2.  There is a possibility that "unanticipated" or "unexpected" adverse effects could follow from changes in weed populations and communities.  Monitoring 
these weeds would be a prelude to discovery of unanticipated or unexpected adverse effects. 
460. In addition, there are several possible purpo ses served for monitoring for "unexpected" or 
"unanticipated" effects, including: 
• Purpose U1.  Document the geographic and temporal pattern of use of the GMHT crop so that there is a database availa ble that would enable retrospective 
epidemiological-like investigations should an "unanticipated" or "unexpected" effect 
be observed.
72   
• Purpose U2. Train personnel who normally visit agricultural fields and natural areas near agricultural fields to be aware of the possibility that agriculture generally and 
GMHT crops specifically may have "unexpected " or "unanticipated" effects.  Inform 
these people of the occurrence of GMHT crops .  Training should include information 
 
70 The use of "tolerance" in this context is different from the use of tolerance as defined either by 
Painter (1958) or Baucom and Mauricio (2004).  In  actuality, these GMHT (genetically-modified herbicide-
tolerant) crops are not damaged by the herbicide, unless the herbicide is applied inappropriately. 
71 Watkinson et al. 2000, Science, 289, 1554-1557. 
72 This was recommended by an NRC committee (N RC 2002, Environmental e ffects of transgenic 
plants: The scope and adequacy of regulation. NAS Press, Wash, DC).  It finds resonance in Annex VII.C.4 of 
Directive 2001/18/EC, but the Annex is not as clear as the recommendations in NRC 2002.  WT/DS291/R/Add.6 
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  about the potential mechanisms by which such effects could possibly arise.  For 
example, "unanticipated" effects of weed co mmunity shifts should receive attention.  
This training will provide the many eyes needed to notice possi ble changes in the 
environment.73 
• Purpose U3.  Document changes in agricultu ral practices associated with the use of 
GMHT crops.  There is a possibility that "unanticipated" or "unexpected" adverse 
effects could follow from changes in agri cultural practices.  Monitoring these 
practices could be a prelude to discovery  of unanticipated or unexpected adverse 
effects. 
461. Clear specification of the purpose of monitoring is probably the most critical step in 
developing a useful monitoring system. 
Monitoring must have a sequel  
462. The act of monitoring should not be an end in  itself.  The information gathered during the 
monitoring activities should be used to make a respon se.  This response should be related to the risk, 
including activities ranging from those to better estimate the risk to those activities to avoid, mitigate or tolerate the risk.
74  Specification of a response is probably the second most critical step in 
developing a useful monitoring system.  Although Annex VII.C.6 of Directive 2001/18/EC states that a response should be considered, it does not require a response. 
Action Trigger  
463. In addition to a sequel, a monitoring system mu st have a well-defined action trigger.  An 
action trigger is a criterion or set of criteria, which if met (or exceeded) according to the information from monitoring, would require taking the response actions.  Without a clear action trigger, it could become quite difficult to determine when monitoring would precipitate a response.   
464. Important logistical issues  include: (1) who will monitor,  (2) who is responsible for 
monitoring, (3) who handles and synthesizes the mon itoring information, (4) who verifies the quality 
of the monitoring, information obtained from monito ring and synthesis of this information, (5) to 
whom are monitoring results reported and at what frequency, (6) how will the monitoring effort be 
sustained, (7) how can monitoring be conducted in a co st-effective manner.  Most, but not all, of these 
logistical issues are recognized in Annex VII.C.3 and 5 of Directive 2001/18/EC. 
465. Important methodological issues  include: (1) what 'endpoint' will be monitored, (2) what 
frequency will monitoring be conducted, (3) what will be the spatial density (grain) of monitoring, (4) 
can monitoring be stratified by potential risk.  A fe w of these issues are recognized in Annex VII.C.3 
of Directive 2001/18/EC.  The endpoint of monitoring is what is actually measured and/or estimated by the people conducting the monitoring.  For exampl e, for weed resistance it could be the frequency 
of resistance genes or resistant phenotypes in the weed population; for non-target effects, it could be total weed biomass, production of weed seeds that ar e normally consumed by skylarks, and so on.  
Choice of endpoint can enable or restrict possible responses.  The frequency of monitoring will depend on several factors, including the anticipat ed response.  If the response involves a series of 
                                                      
73 This was recommended by an NRC committee (N RC 2002, Environmental e ffects of transgenic 
plants: The scope and adequacy of regulation. NAS Press, Wash, DC).  It finds resonance in Annex VII.C.3.2 of 
Directive 2001/18/EC, but the Annex is not as clear as the recommendations in NRC 2002. 
74 This point has been made emphatically in NRC 2001 .  Ecological monitoring of genetically modified 
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                                                       processes that would take several years to comple te, it might be appropriate to increase monitoring 
frequency so that the monitoring process does not in troduce additional delays in responding to a 
potential threat.  The grain of monitoring will be depend on several factors, including the expected 
grain of the effect being monitored.  For example, if regional weed resistan ce is the concern, then 
monitoring can be done at a regional scale.  If weed resistance on farms is the concern, then 
monitoring will probably need to occur at a finer grain.  Weed community shifts might be done on 
several spatial scales.  If the adverse consequences are focused on bird species, regional monitoring 
may be sufficient.  If they are focused on less mob ile species, then a finer grain will be necessary.  
Finally, it will be essential that m onitoring is stratified so that it o ccurs at places and times most likely 
related to possible risks.  Monitoring is costly a nd monitoring resources must be allocated efficiently.  
For example, monitoring for unanticipated effect s could be stratified according to the geographic 
distribution of the GMHT crop.  Monitoring coul d occur mostly or only at places where the GMHT 
crop is used considerably, with a threshold inte nsity of usage determining the distribution of 
monitoring effort. 
466. Monitoring for unanticipated or unexpected effects.  The first step in developing a monitoring 
system for these possible effects is to specify clearly wh at effects, if any, are anticipated or expected.  
Without this clear statement, it will not be possible to determine if any observed effect is unanticipated or unexpected.  For example, if no adverse effects ar e anticipated or expected, then it 
must be granted that any subsequently observed effect must be considered unanticipated or 
unexpected.   
467. General critique of proposed monitoring plan (EC-66/At.62).  (1) Specific purpose of the 
proposed monitoring plan is to monitor for unanticip ated or unexpected effects.  It does not address 
concerns associated with weed  resistance or chang es in weed populations and communities, as 
indicated by the EC officials.  The purpose of th e monitoring for unanticipated or unexpected effects 
is not entirely clear.  Consequently it is difficult to know how the proposed monitoring will enable the 
identification of any unanticipated or unexpected e ffects.  (2) The proposed response is to conduct a 
scientific evaluation of the observed potential unanticip ated effect to confirm that it is in fact an 
unanticipated effect.75  While it is stated that the response should be proportionate to the risk, it is not 
clear what procedure and standard will be used to determine a proportionate response.  Second is 
unclear who is responsible for conducting the scien tific evaluation and how to ensure that this 
information will be collected in a timely fashi on, who will have access to the information, who 
determines the adequacy of the design of the evalua tion and so on.  (3) The triggers for initiating a 
scientific evaluation are not clear.  It would be folly to initiate a scientific evaluation of all possible 
observations of possible adverse effects.  Ho w will these be screened to trigger a scientific 
evaluation?  When does the scientific evaluation provide sufficient evidence to trigger remedial 
action?  These issues are not resolved in the prese nt proposed monitoring plan.  (4) The logistical 
issues are better specified than the other component s of the proposed plan.  Important weaknesses in 
the proposal include lack of specification for how the seed supply and distribution network will be 
linked to the monitoring procedures, that key exte rnal networks are not committed to monitoring, 
procedures to verify the quality of monitoring, in formation from monitoring and synthesis of this 
information, short time span and long intervals for reporting, and so on.  (5) Methodologically, the 
proposal has several important weaknesses.  No e ndpoint is specified and it is not clear how people 
who might be monitoring would recognize an unantic ipated effect.  In this case these people should be 
informed that any adverse effect mu st be considered an unanticipated  effect, and should be reported.  
The frequency and grain of these obser vations is unclear.  There seems to be little stratification of 
effort by potential risk.  
 
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  Dr. Squire  
468. The EC's SCP opinion is generally positive about  the application, whereas the EC member 
states raise several objections. The issue of antibiotic resistance was considered in the SCP's opinion 
(EC-66/At.53) and found not to pose risk, but ther e is now widespread perception that antibiotic 
resistance should not be introduced through GMHT products. The basis of objection by some member 
states is that general effects of HT cropping on farmland habitats are uncertain, and this applies 
whatever the species or the land area it occupies. However, the context for this biotech product in 
cotton is very different from the context of those products which are varieties of oilseed rape. Cotton 
occupies a very small area in Europe and does not present potential problems of the type associated with oilseed rape or even maize or beet (Table 1). This notwithstanding, and as in other instances, unless criteria can be given, from both the proposer and objector as to what is a desirable or acceptable comparator, then progress with the discussion is impossible, as it became in this instance.  
469. There appeared to be no monitoring plan in the original proposal, and in the 2003 document, 
the relevant section indicated that little specific m onitoring was necessary b ecause of the low risk. 
Monitoring the effects on habitat would be feasibl e but suitable criteria on which to base monitoring 
have not been proposed or agreed by either side.  
Amylogene starch potato  
C/SE/96/3501  (EC chronology 67) 
 
Question 25:  Given the information before the Panel, including the application (EC-67/At.13-
44), and additional information provided by the notifier (EC-67/At.51, 57, 61-63, 75-83, 87, 92-93, 94-95, 101, and 103), was the information regarding molecular characterisation, toxicity, protein analysis, animal feed trials, effects on non-target organisms, bleomycin resistance, and 
substantial equivalence requested by the Scient ific Committee for Food (SCF) (EC-67/At.84-86, 
96, 98, 100, 102, 104, 105 and 106), necessary to support a valid safety assessment? 
Dr. Nutti  
470. Based on the information provided by the applicant in EC-067/At.13-44 and the analysis done 
by the EC SCP and following the Codex Guidelines,  it is clear that the information required was 
necessary to support a valid safety assessment. The no tifier failed to provide information on several 
fundamental issues concerning safety such as substantial equivalence, toxicity, protein analysis and 
animal feeding trials. 
Dr. Andow  
Necessity for valid safety assessment : 
471. In this answer I will address only the non-target or ganism part of the question.  The transgenic 
potato produces elevated concentrations of amyl opectin by blocking starch synthesis and also 
expresses nptII.  Based on molecular analysis there ar e multiple copies of the transgene in the plant. 
472. EC-67/At.84, 4 February 1999, First request from SCP to Amylogene for clarification: 
In conclusion, I would like to inform you that the Committee will only consider at 
this stage additional data that is of a non-confidential nature.  In this respect, I would be obliged if you would include a statement to  this effect in the covering letter with 
any data you may wish to submit in r esponse to the Committee's questions.  The WT/DS291/R/Add.6 
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                                                       reason for this is that it is not possible at this stage to repeat the notification 
procedure, which provides for agreement between the notifier and the competent 
autority on confidentiality (Article 19 of  Council Directive 90/220/EEC).  However 
should you consider that certain of the data requested by the SCP is of a confidential 
nature and that you would prefer not to submit the data without obtaining a 
confidential status, the SCP will then complete its evaluation on the basis of the available data.
76
8) No data are provided on the safety of modified crops to non-target organisms.  
No risk assessment has been made.77
3.5. Environmental Aspects 
3.5.1. Geographical relevance of data 
Wherever possible data should be provi ded from field experience in those 
geographical regions where the GM plant will be grown commercially to reflect 
relevant meteorological, soil and agronom ic conditions.  Where data from field 
studies on other continents are supplied,  the notifier should submit a reasoned 
argument that the data is applicable to Europe.  Bridging studies may be particularly 
useful. 
3.5.2. Impact on non-target organisms 
Clear and well-defined risk assessments should be carried out for each of the different 
functional environmental compartments that are exposed to the GM plant;  this will 
depend on the specific crop and if any parts of it will remain in the environment after 
harvest.  For example, exposure should be estimated to soil organisms and function 
(e.g. earthworms, micro-organisms, leaf litter breakdown), non-target arthropods 
(including pollinators, beneficial arthr opods), grazing birds and mammals or, if 
appropriate, the aquatic environment.  Th is risk assessment should take account of 
where in the plant the inserted genes are expressed and the consequent exposure of 
non-target organisms.  The assessment s hould also address the fate of the expressed 
substance in those environmental compartm ents where they are introduced and may 
cause exposure of non-target organisms (e.g. in soil after the incorporation of plant 
material).  Data on the comparative su sceptibility of the GM plant to pests and 
diseases compared to the non-modified plants  are useful together with observations 
on agronomic performace during greenhouse and experimental release trials.78
473. The SCP indicated that no non-target assessment had been conducted, and provided guidance 
(3.5) for completing such an assessment.  At this time, possible risks could arise from the transgenic 
plant or processing wastes, including fruit juices and fruit water. 
474. EC-67/At.86, 12 July 1999, Draft opinion of SCP 
6.3.3. Safety to Non-Target Organisms :  There are no data on safety of the 
modified crops to non-target organisms.  However, the results of growing trials 
 
76 Page 1.  All page references in this answer re fer to the page number in the relevant pdf file. 
77 Page 3. 
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                                                       suggest neither greater susceptibility nor great er resistance to pests and diseases than 
non-GM potato lines.  In view of this and the equivalent composition of the modified 
potato line, it is considered that no adve rse effects on non-target organisms would be 
expected from cultivation of the GM high amylopectin potato line EH92-527-1.79
475. The SCP draft opinion reverses their previous opinion that there has been no risk assessment 
for non-target effects.  In what follows, I lay out th e findings that appear to lead to both the original 
opinion and the reversal, and evaluate the scientific basis for each. 
476. EC-67/At.77 1 April 1999, Amylogene provides SC P working group with the full application 
as well as additional data.  This is copy of EC- 67/At.14 7 May 1998, Summary statement of CA of 
Sweden 
Environmental effects of the genetically  modified potato clone (EH92-527-1) 
In laboratory and field trial studies no differences in behaviour of clone EH92-527-1 have been observed compared to its parental  variety.  The genetically modified clone 
is not considered to have increased surviv ability or competitiveness in agricultural or 
natural environments.  The analysis carried  out to investigate whether the modified 
clone displayed any increase or decrease in frost tolerance did not indicate any such changes.  The parental variety has a low flowering frequency and thus a low seed production, and with respect to this the modified clone does not display any change.  Compared to the parental variety, no data indicate that the genetically modified clone 
possess any alteration in its potential to sp read its genes, neither through sexual 
crosses not horizontally to sexually in-c ompatible species.  No unexpected 
(pleiotropic) effects resulting from the modi fication of the clone in question have 
been identified.  In conclusion, the modified clone does not exhibit any differences in 
environmental behaviour as compared to the parental variety (cv. Prevalent), and is 
therefore not considered to pose any risk to the environment.
80
477. The summary risk assessment statement of the CA of Sweden on 7 May 1998 does not 
mention specifically any non-target risks. 
478. EC-67/At.79 (also EC-67/At.17) Part I B.781, Potentially significant interactions of the plant 
with other organisms than plants in the ecosystem where it is normally grown, including information 
on toxic effects on humans, animals and other organisms .  Here the notification suggests that changes 
in glycoalkaloids or nitrates may be causes of non-target  effects.  The extant literature is reviewed for 
effects of glycoalkaloids and nitrates on organisms.   Mammals, birds, insect pests of potato, nematode 
pests of potato, pathogenic fungi of potato, pathogenic bacteria of potato and infectious viruses of 
potato are listed.  There is only citations of the toxi c effects of glycoalkaloids to some of the listed 
species.  No citations to effects of nitrate are mentioned.   
 
79 Page 6. 
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                                                       479. EC-67/At.79 (also EC-67/At.17) Part I D.9 
9. Potentially significant interaction with other, not modified organisms 
In potatoes normally existing toxic and anti- nutritional substances are glycoalkaloids 
and nitrates.  The interaction with other orga nisms has been described  in Part 1, B.7..  
In D.7, in Annex 8 and in Part 3 it is show n that the contents of these substances have 
not been changed as a consequence of the modification.  On that account, the 
modified potato clone, EH92-527-1, does not affect other organisms in another way 
than what the unmodified recipi ent cultivar, Prevalent, does. 
The modified clone, EH92-527-1, is characterized by two changes compared to the recipient clone.  Those are resistance to ka namycin and the lack of amylose.  Because 
of the latter, the content of amylopectin has been increased to >98%.
82
There are no reasons what so ever to s uppose that the changed starch composition 
(>98% amylopectin) should cause any danger for other non-modified organisms, 
including humans.  There are already pl ants, in which this trait has occurred 
spontaneously or by induced mutations, e.g. maize and barley.  Further more 
"amylopectin starch" can be produced from normal potato starch by chemical treatment.  No un-desired side-effects have been observed (Annexes 5 and 7).
83
480. Specifically amylopectin starch o ccurs in large quantity in the so-called waxy maize varieties 
and is also found in quantity in some rice, barley and sorghum varieties. 
481. EC-67/At.79 (also EC-67/At.17) Part III D 
D. THE RISK THAT THE PLANT CAN BE MORE SUSCEPTIBLE TO PREDATORS AND DISEASES. 
The establishment and development of plants  from seed of the clone EH92-527-1 has 
been studied in comparative trials in 1995, and in observation trials in 1993, 1994, 
1995 and 1996.  In all trials it has been shown that the establishment and 
development of plants are equal to the recipient clone both above and below ground.  During the growing season, both the modified potato clone and the recipient clone were exposed to attack by insects and diseases, mainly potato late blight.  In order to 
avoid such damages, treatments were applied according to the requirements of the recipient clone.  There were no observations indicating that the transgenic clone is 
more (or less) susceptible to any pest or di sease than the recipient variety.  (Annexes 
2, 10, 13, 14, 15 and 20.)
84
 
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                                                       482. EC-67/At.80 (also EC-67/At.17) Part III E 
E. THE POSSIBILITIES FOR NEGATIVE ECOLOGICAL AND OTHER 
EFFECTS WHICH ARE NOT RELATED TO WEED CHARACTERS 
Such effects have not been observed during any of the trials.  It is not expected that 
such effects should occur as a consequence of the modifications present in EH92-527-1 (Annexes 2, 10, 13, 14, 15, 20).
85
483. It should be clear that the relevant informa tion is in Annexes 2, 10, 13, 14, 15, and 20. 
• Annex 2. The Swedish Seed Testing and Certification Institute: Statement on variety distinctness 
• Annex 10. Observations in practical cu ltivation of conventional Prevalent and 
transgenic Prevalent EH92-527-1, 1994- 1995, and in laboratory freezing tests 
1996/1997 
• Annex 13.Report about field trial with transgenic potatoes 1993 
• Annex 14. Report about field trials and seed production with transgenic potatoes 1994 
• Annex 15. Report about field trials and practical cultivation with transgenic potatoes 1995 
• Annex 20. Report about field trials and practical cultivation with transgenic potatoes 1996 
484. Annex 2 is missing from the materials.  This annex is the Swedish Seed Testing and 
Certification Institute: Statement on variety distinctness,  so is unlikely to have information relevant to 
biosafety risk. 
485. Annex 10 contains detailed information about  1994 and 1995.  Annexes 14 and 15 provide 
only summary information related to potato seed pr oduction, and have no info rmation relevant to 
biosafety.  Annex 20 provides only summary inform ation related to potato seed production, and has 
no information relevant to biosafety.  Annex 13 provides detailed information about 1993 results.  
However, only four clones were unt ransformed standards and 79 clones were transformed.  This study 
was too small a scale to provide reliable information related to biosafety. 
486. EC-67/At.81 (also EC-67/At.27), Annex 10.   The notification concludes as follows: 
Conclusions of practical cultivation in 1994 and 1995 
The potato clone Prevalent 92-527-1 has not differed from conventional Prevalent in the cultivations observed. 
– Normal morphology 
– Similar reactions to chemicals 
 
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                                                       – Similar resistance to diseases 
– Similar sensitivity to frost in early summer as well as in fall 
Three comparative trials with comparisons of yield and starch contents were made in 
1996 with conventional Prevalent and the clone 92-527-1 (Annexes 8 and 20). 
Investigations regarding resistance to nematodes, performed at the Agriculture 
Laboratory in Lyckeby, revealed identical  resistance to Globodera rostochiensis, 
pathotype Ro1Ro4, in both clones.86
487. I will show that the conclusion that the clones are similar in resistance to diseases has not 
been scientifically demonstrated.   
488. EC-67/At.81 (also EC-67/At.27), Annex 10.  Summa ry of data.  Five plantings are reported, 
two in 1994 and 3 in 1995.  At the 1994 Skara planti ng, there were bad growth conditions and yield 
was low and seed quality was bad.  Fields were treated  with fungicide and no late blight occurred.  At 
the 1994 Norra Sunderyn planting, growing conditions were good, but there was no late blight in the 
field.  At the 1995 Sofielund planting, growing conditions, plant development and yield were 
comparatively bad, late blight was similar betw een transgenic and non-transformed varieties, and 
there were no attacks of pests or parasites.  At the 1995 Habo planting, soil structure was damaged, 
yield was low and late blight was controlled by no rmal fungicide applications.  At the 1995 Norra 
Sunderbyn planting, growing conditions were good, but no attack by late blight or other diseases were 
observed. 
489. To show that the clones are similar in resist ance to diseases, the diseases must be present and 
the plants must be healthy.  Of the five plantings  with sufficient informati on to evaluate (paragraph 
488), none meet these two conditions.  If we co nsider only those plantings with disease present, 
disregarding the quality of the plants, one planting (1995 Sofielund) would suggest that late blight 
resistance was similar.  
490. It can be concluded that there is no evidence in  the written record to support the statement in 
the draft SCP opinion (EC-67/At.86) that "the resu lts of the growing trials suggest neither greater 
susceptibility nor greater resistance to pests and di seases than non-GM potato lines."  Indeed, even if 
the statement is restricted to refer only to late blight, it is not supported by the evidence.  It is possible 
that the notifier presented information verbally to th e SCP on this issue that is not recorded in the 
written record, but in this case, the SCP should have mentioned this.   
491. Thus it can be argued that a request for additional non-target information was 
scientifically justified in 1999 and remains justifiable even today.   
492. However, it is useful to consider if there is any evidence that points to the possible existence 
of non-target effects.  The notification identifies two possible routes by which non-target effects could 
result: changes in glycoalkaloids or nitrates.  Ne ither of these is likely for amlyopectin potatoes, 
because as detailed in the responses to questions in EC-67/At.83, the amylopectin potatoes do not have different concentrations of nitrate or glycoa lkaloids compared to non-transformed potatoes.  Two 
other lines of argument can be considered.  First, because amylopectin occurs in other crops, have there been any observable adverse effects from grow ing these crops?  Second, is there any route by 
which amylopectin or nptII directly could cause a nd adverse effect?  Issues related to nptII are 
 
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                                                       extensively covered in the notifica tion, and concerning direct non-target effects, the notification 
appears to present a strong case that such effects are lik ely to be small or absent.  In the paragraphs 
below I will take each of these other points in order. 
493. Other crops.  Using Agricola and CAB Abst racts, I found 1213 references to waxy 
maize/corn during the past 25 years.  I looke d at 250 of them and found seven references87 to the 
effects of waxy corn on farm animals.  Waxy corn does effect animal digestion, but the effects may be 
possibly beneficial in some animals.  There were  no studies published on effects on other organisms.  
This provides some evidence that amylopectin potat oes may have little adverse effect on mammals.   
494. EC-67/At.83.  Effects on nematodes.  The notifi cation reports a summary of an experiment on 
cyst nematodes.  The conclusion was that the transgenic potato had no effect on the nematodes tested.  
The full data are not included in the notification, and there was no request for the data by the CA or Sweden or the SCP.  Without the full data, it is not  possible to evaluate the scientific merit of the 
conclusion. 
Reply to questions forwarded by the Austrian Competent Authority. 
Your question regarding experimental tests with non-target organisms, in order to 
verify our statement that the clone cannot be supposed to cause any danger to other non-modified organisms: 
As we mentioned during the technical mee ting in Brussels on July 23, no such tests 
have been performed.  We are still convin ced that the transformed clone cannot be 
supposed to cause such harm.  During growing of the clone we have not been able to note any different reactions in the interaction between the potato plants and the insects and nematodes mentioned.  The only analysis made confirms that the transgenic clone carries the same resistan ce to cyst nematodes (Ro1,Ro4) as does the 
recipient variety.  It should also be mentioned that one goal for potato breeders 
working with conventional methods (not gene  technology) is to introduce resistance 
to parasitic organisms like beetles and aphids.
88
495. EC-67/At.83.  Fruit water as a possible source of risk.  There appears to be little 
environmental risk associated with fruit water. 
 
87 Snow,-J.L.; Stein,-H.H.; Ku,- P.K.; Trottier,-N.L.  2004. Amino acid digestibility and nitrogen 
utilization of high oil, high lysine, and waxy maize fed to growing pigs.  Animal feed science and technology 
113: 113-126.  Akay,-V. ; Jackson,-J.A.-Jr. ; Harmon,-D.L.   2002.  NutriDense and waxy corn hybrids: effects on 
site and extent of disappearance of nutrients in sheep.  J-anim-sci. 80: 1335-1343.  Many factors examined, 
generally few significant effects, but some differences reported.  Akay,-V. ; Jackson,-J.A.-Jr.   2001.  Effects of 
NutriDense and waxy corn hybrids on the rumen fermentation, digestibility and lactational performance of dairy 
cows.  J-dairy-sci. 84: 1698-1706.  Many factors examined, generally few significant effects, but some 
differences reported.  Dado,-R.G.  1999.  Nutritional benefits of specialty corn grain hybrids in dairy diets.  J-
anim-sci. 77 (suppl.2): 197-207.  Re view. Variable effects reported.  Reid,-C.A. ; Hillman,-K.   1999.  The effects 
of retrogradation and amylose/amylopectin ratio of starches on carbohydrate fermentation and microbial 
populations in the porcine colon.  Anim-sci . 68 (pt.3): 503-510.  Potentially positive effects on young pigs.  
Kleesen,-B. ; Stoof,-G. ; Proll,-J. ; Schmiedl,-D. ; Noack,-J. ; Blaut,-M.   1997.  Feeding resistant starch affects fecal 
and cecal microflora and short-chain fatty acids in rats.  J-anim-sci . 75: 2453-2462.  Potentially detrimental 
effects on rats.  Schroeder,-J.-W.  (Jerome Wilfred) ; Park,-C.-S. ; Marx,-George-Donald.   199-.  Waxy corn as a 
replacement for dent corn in diets of lactating holstein cows:  final summar y.  Fargo, N.D.: Animal and Range 
Sciences, North Dakota State University, 14, [8] leaves:  ill. 
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                                                       It is necessary to specify the composition of potato processing effluent, count plant 
cells and provide information about the h ealth and environmental safety of this 
effluent, in particular for soil bacteria flora, and the process used. 
Objection raised by the CA of France. 
We assume that the objection concerns the "fruit water" which is spread over fields as 
a fertilizer. 
The fruit water consists of water that is added to the process for washing of the potatoes and for washing of the starch, and a small proportion of fruit juice that is not 
added to the pulp. 
The fruit water contains small amounts of potato skin and flesh residuals, mainly 
fibres and cells, and water solubl e salts of potato constituents. 
Consequently, nothing is added to the e nvironment that was not present in the 
potatoes, and as the water content of the fruit water is > 98%, the amounts of potato 
material is very small. 
It should be noted that fruit water from the st arch industry has been  used as fertilizers 
for more than 10 years in Sweden, without causing any problems. 
The only constituent of the fruit water that could be a concern is the presence of the 
nptII gene causing resistance to aminoglycosides (antibiotics).  In Part I, Section D, paragraph 9; Part 3, Section C; Annex 1 and Annex 22 of the notification, and in 
attachment 8 of this document it has been shown that this cannot possibly be assumed to cause any harmful effects by adding antib iotic resistance of any significance to the 
soil bacteria population.
89
496. EC-67/At.83.  Vitamin C.  Amylopectin potato has higher Vitamin C content than the 
untransformed clones, although the concentration re mains within the normal range of variation for 
potato.  Even though it is in the normal range, it is elevated, and could possibly cause a risk.  While I 
consider the following scenario unlikely, there is a possible risk pathway.  Holometabolous insects 
require enough Vitamin C to complete pupation.  If pupation is limited for any insect on potato, it 
could have a higher survival rate on the amylopectin varieties.   
• The higher content of vitamin C indicated in the notification is confirmed.  The difference between EH92-527-1 and Prevalent is even more pronounced.
90 
• In both years the content of vitamin C was significantly higher in the transformed 
clone than in the non-transformed variety.  This is explained in attachment xx, vitamin C being involved in the sugar and carbohydrate synthesis of the plant.  The higher content of vitamin C is not considered  to have any impact on animal health or 
on the environment.  It should also be ob served that the vitamin C contents measured 
are within the range of natural variation of the recipient clone (table 9 of the notification).  Please note that the values reported in annex 8 of the notification and 
attachment 1 of this document are expressed as mg/100 g dry matter, while the 
 
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                                                       corresponding values of table 9 of the notification are expressed as mg/100 g fresh 
weight.91 
Exhaustive comments on the observed significant differences in Vit.C, dry matter, 
fructose, glucose and sacharose content, associated with the deliberate modification 
of the starch synthesis. 
Objection raised by the CA of Italy 
EH92-527-1 produces less starch than the mother variety Prevalent.  This is probably because of its inability to synthesise amylose and not using the available sugars to 
synthesise amylopectin instead.  During tuber starch accumulation the tuber is a sink 
for sugars from the photosynthesis.  If those sugars are not incorporated into starch it might result in the higher content of mono- and disaccharides in EH92-527-1.  
Mutations that affect starch synthesis often result in increased levels of sugars.  A mutation with great effects on starch synthesis is where ADP-glucose 
pyrophosphorylase is affected.  This enzyme  gives the first commited step in starch 
synthesis and antisense inhibition of the ge ne results in potato tubers with decreased 
dry matter, decreased starch content and increased accumulation of soluble sugars 
(Müller-Röber et. al.).  The modification is not the same as in the present Notification 
but points in the same direction.  A decreased ability to form starch results in 
increased levels of soluble sugars. 
When it comes to Vitamin C, another high amylopectin potato clone is currently being investigated.  This new transgenic clone has the same levels of Vitamin C as EH92-527-1.  It is to be noted that the c ontent of Vitamin C in EH92-527-1 is within 
the levels normally observed in potato.  A possible explanation is that the higher 
Vitamin C content is an associate effect of  elevated levels of mono- and disaccharides 
since ascorbic acid is most probably synt hesized from simple sugars in a few 
metabolic steps in plants.  In a resent publication (Wheeler et. al.) the pathway 
leading to Vitamin C in plants was inves tigated.  In the pathway presented, glucose 
and fructose are starting materials for the biosynthesis of Vitamin C.  Therefore an increase of substrate levels might very well result in the significant increase of Vitamin C observed in the present Notification.
92
497. The transformed amylopectin potato has several transgene loci.  Although most of the issues 
now appear to be resolved, the discussion on molecu lar characterization implied that the plant might 
have been producing an unidentified protein fro m one of these other transgene loci.  If such 
production had occurred, it could lead to non-target risks.  
498. From the alternative perspective, it is difficult to believe that amylopectin potato would cause 
a significant adverse effect on non-target species.  Aside from the adverse effects of growing potato, it is not clear what kind of change to potatoes woul d result in a significantly greater adverse effect.  
Moreover, if any adverse effects do become manifest, it would be possible to withdraw potato from the market and expect that the transgen ic potato would rather quickly die out. 
499. In summary, the SCP was justified in asking fo r a non-target risk assessment on 4 February 
1999.  In light of the data in front of it at the time, it was not justified in concluding on 12 July 1999 
 
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  that amylopectin potato would have no adverse effect s on non-target organisms.  The scientific data 
provide no evidence that there is an adverse effect , but the data are not strong.  Hence the scientific 
data and scientific arguments can divide on whether there is a necessity for additional non-target risk 
assessment.  On the one hand, some could argue credib ly that adverse effects on non-target organisms 
are unlikely, and no additional assessment is needed.  Others could argue credibly that adverse effects 
are possible, requiring data to address the few loose ends identified above.  In no case, however, could 
it be credibly argued that adverse non-target effects are likely to or in fact do occur, and therefore an extensive non-target risk assessment is NOT necessary. 
500. The SCP requested information from the notifie r on 4 February 1999.  The notifier provided 
the full notification on 4 January 1999.  The 31 days th at elapsed is a reasonable, if not rapid response 
time. 
Dr. Healy  
Note: the question specifies the Scientific Committee for Food, however there is no mention of this 
committee in any of the documents, the numbered a ttachments all refer to information requested by 
the Scientific Committee on Plants (SCP). I have answ ered this question in relation to the information 
requested by the SCP. 
 
501. Response :  Following receipt of the notification from Amylogene seeking approval for 
Amylogene starch potato clone EH92-527-1 in A ugust 1996, the lead CA (Sweden) expressed a 
favourable opinion in May 1998.  The dossier w as then sent to the European Commission and 
distributed to other Member States for comment .  A number of comments and requests for further 
information were received from various Member St ates.  In September 1998 the EC requested the 
SCP to consider whether there was any reason to be lieve that the placing on the market of the starch 
potato clone EH92-527-1 would be likely to cause any adverse effects on human health and the 
environment.  
502. The dossier and additional information were supp lied to the SCP in January 1999.    Between 
February 1999 and November 2001, the SCP made ni ne further requests to Amylogene for additional 
information or clarification of information.      
503. Background:  Potato clone EH92-527-1 contains two novel genes, an antisense Granule 
Bound Starch Synthase gene (gbss), and a marker gene, the nptII gene.  The nptII gene, which is 
widespread in nature, is widely used in GM plan ts and is well characterised.  The gbss gene was 
isolated from the potato and was reintroduced into th e potato in the antisense orientation to silence the 
endogenous gbss gene, which is involved in the synth esis of amylose.  This results in the production 
of starch with high amylopectin content.  No protein is produced from this introduced gene.  
504. The potato clone EH92-527-1 was generated pr imarily to produce starch for industrial 
purposes. The by-products of this process, potato pulp , potato juice and potato water, were intended to 
be used for animal feed and irrigation purposes.  No products derived from potato clone EH92-527-1  
were intended for use as human food.  WT/DS291/R/Add.6 
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  505. Molecular characterisation: 
4 February 1999 (EC-67/At. 84): the SCP requested further evidence that the plasmid 'backbone' 
DNA was not incorporated into the genomic DNA: 
 
More convincing evidence is required that speci fic elements of "backbone" DNA are or are not 
incorporated 
(A) The dossier lacks a detailed map or tabl e describing the DNA backbone outside T-DNA 
borders. One or other should be provided. Or igins of all open reading frames and control 
elements should be given and a risk assessment  provided for each. The notifiers should clarify 
the antibiotic specificity of the nptII gene incorpor ated into the backbone of the binary vector.  
(B) There are some confusing and inconclusi ve PCR analyses to demonstrate absence of 
vector sequences flanking the border regions. Appr opriate controls are lacking (i.e. positive 
PCR's are carried out on plasmid DNAs instead of control genomic DNAs or mixtures of 
genomic and plasmid DNA). The use of overlapping  probes in Southern analysis is preferable. 
(C) Southern blots have been used to determin e integration of genes/ gene fragments outside 
left and right T-DNA borders. A cocktail of probes has been used. However, there is no positive 
control to demonstrate that all elements of the probe are working.  
(D) Also related to Southern analysis, only 2 probes have been used to determine copy 
number. No probes have been used co vering the nos gene for example.  
 
506. Response :  The data in the original dossier concerning the molecular characterisation of 
potato clone EH92-527-1 included Southern blots of genomic DNA from both the transgenic potato 
and its parental line, using insert and backbone spec ific probes. Positive and negative controls were 
also performed. PCR analysis of the junction re gions between the insert and the genomic region 
indicated that no large fragments of introduced DN A were present at these junctions. However, no 
sequence data were provided.   
507. Southern analysis was originally conducted using a cocktail of backbone specific probes, 
although this does not conclusively show the absen ce of plasmid backbone sequence. Evidence was 
provided that the company intended to supply conclusive data showing no plasmid backbone 
sequence is present is potato clone EH92-527-1 and DNA sequence of the junction regions (EC-
67/At. 83). However, it is not clear from the docum ents provided (Exhibit EC-67) whether this data 
was actually provided to the EC or the SCP. This in formation, together with the data in the dossier 
provided to the SCP would have made the requests at A), B) and C) unnecessary. 
508. A detailed description of the DNA backbone outsi de of the T-DNA border is not warranted 
(part A) if sufficient evidence is provided to show  that no backbone DNA is present in the DNA of the 
GM potato.  
509. The optimal number of probes to be used in S outhern hybridisation is determined on a case-
by-case basis (part D). Potato clone EH92-527-1 contains two additional genes the gbss gene and the nptII gene, and therefore as a minimum it would be r easonable to use probes to detect each of these 
genes. The company used probes specific for the gbss gene and its promoter region. Due to the presence of an endogenous gbss gene, this experimental approach was less than optimal, however, the 
use of the non-transgenic potato DNA as a negative c ontrol allowed identification of the endogenous 
gene. Although the initial selection procedures confirm the presence of the nptII gene, probes 
detecting the presence and copy number of this gene  in potato clone EH92-527-1 would be required.  WT/DS291/R/Add.6 
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  510. Toxicity and animal feeding trials 
4 February 1999 (EC-67/At. 84): the SCP requested information on the use of potato pulp for animal 
feeding in different MS, including information on targ et animals. The SCP also requested justification 
for the absence of a feeding trial using the GM potato: 
 
The notifier should provide information on possible application of pulp for animal feeding in 
different EU Member States. Target animals etc. 
 
The notifier should justify the absence of an y toxicological data involving relevant animal 
feeding trials. 
 
511. Response : Potato pulp has a long history of safe use as stock feed. The pulp of the non-
transgenic parental line had been used in Sweden as cattle feed since 1988 without known harmful or 
negative effects. Evidence was provide that the nutritional composition of tubers from potato clone 
EH92-527-1 was similar to that of the parental line and within the normal reference ranges for 
commercial potatoes, except for those intended di fferences related to starch composition. The 
Swedish Board of Agriculture notified its approval of the transgenic potato for placing on the market in May 1998.  
512. The starch present in the pulp from EH92-527-1 differs from common potato starch 
(composed of amylose and amylopectin) only by lack of the amylose component. The company 
provided data and estimates of consumption rates in cattle of potato pulp. As amylose usually makes up 20-25% of the total starch in potatoes, if pul p from potato clone EH92- 527-1 were to be used, 
cattle would consume no amylose and more amylopectin per day.   
513. Other agricultural crops, such as waxy maize, contain starch with similar levels of 
amylopectin to potato clone EH92-527-1. Rice, barley and sorghum also contain high levels of amylopectin. Furthermore, the potato pulp used as stockfeed is a by-product of the starch industry and would therefore be unlikely to contain high levels of starch.    
514. Given the compositional analyses of the transgenic potato, the similarity in starch 
composition with other plant derived animal feeds, and the absence of starch remaining in the potato 
pulp, feeding studies using potato clone EH92-527-1 in various livestock species are not necessary to 
support a valid safety assessment. 
9 March 2000 (EC-67/At. 99): in light of the presen ce of an ORF in potato clone EH92-527-1 (ORF4, 
discussed below), the SCP requested  an animal feeding study: 
Evidence should be provided regarding the safety of the material for animal feeding since part 
of the by-products will be used for animal feedin g. This is of relevance given the presence of a 
number of ORFs which show significant homolo gies to known coding regions. The safety may 
be assessed by performance of a 90 day feeding tr ial with laboratory animals administered diets 
with different levels of potato pulp (concentrated). 
515. Response : Further molecular characterization data identified a putative open reading frame 
(ORF, designated as ORF4) in the transgenic potato. Although transcription was detected, there is no 
evidence that ORF4 is translated into a protein.  Potato tubers are predominantly composed of 
carbohydrate with only minimal amounts of protein.  In this case, the transgenic potato has been 
shown to be compositionally equiva lent to conventional varieties, except for the intended difference  WT/DS291/R/Add.6 
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  relating to the starch component. Feeding studies  using target livestock species will not add 
substantially to the safety assessment because low dietary exposures to potato proteins would not 
yield meaningful results that could be validly interpreted.  
516. Protein analysis 
4 February 1999 (EC-67/At. 84): the SCP request ed information on the expression of any novel 
proteins in potato clone EH92-527-1: 
 
In addition to the requirement for conclusive  Southerns for components of backbone DNA the 
Committee would prefer to see Northern/Western analysis where appropriate. For example, the 
expression of the nptII  gene and other open reading frames incorporated into the GM plant. 
 
517. Response :  Western analysis showing the lack of a gbss gene product in potato clone 
EH92-527-1 was provided. These results demonstrate the effectiveness of the genetic modification. 
Given that the introduced antisense gbss gene has a silencing function, the results of Northern 
analyses would add little to the assessment of safet y of the transgenic potato. Messenger RNA from 
the endogenous gbss gene would normally be detect ed and no additional safety concerns would be 
raised by the presence of the antisense gbss transcripts.   
518. However, the dossier contained no data on the expression of the nptII gene. As the only novel 
gene expected to be expressed in the transgenic  potato, data and information on the expression of 
nptII would be required. Rather than Northern analysis, antibody based techniques (such as ELISA) 
would be sufficient to dete rmine the levels of APH(3')II expressed in the tubers. 
519. Several other ORFs are present in the inserted DNA.  In the first instance, bioinformatic 
analysis of any hypothetical polypeptides would be an appropriate means of assessing the significance 
of these in the potato. Depending on these resu lts and the presence of any putative regulatory 
elements, Northern analysis may be justified. This  analysis would be particularly important where 
significant homology with known protein toxins or allergens was identified, or where information from other parts of the safety assessment indicated a potential safety issue. 
520. ORF4 :  Over the period from June 1999 to November 2001, the SCP required further 
information on an identified ORF in the inserted DNA, designated ORF4. ORF4 lies between the 3' 
end of the nptII gene and the nospA element (the polyadenlation signal ) and is not in the same reading 
frame as nptII.  ORF4 was identified as having some homology to the bleomycin resistance protein of Tn5 (E. coli) and the ornithine cyclodeaminase protein (from Agrobacterium tumefaciens).  
3 June 1999 (EC-67/At. 85): the SCP request ed the following information from Amylogene: 
ORF analysis indicates homologies within ORF4 to the bleomycin resistance protein of Tn5.  
Bleomycin is a chemotherapeutic used in cancer treatment. The SCP wishes to know the 
significance of the presence of this ORF with re spect to the expression of a protein and to the 
possibilities of transfer of a functional bleomyci n resistance gene to non-target organisms. This 
could be determined by Northern blot analysis of potato leaves and tubers.   
 
521. Response :  The safety assessment includes an evaluation of the significance of unintended 
translation products arising from the genetic modification on human health and safety. Evidence 
would be required to ascertain whether expression products could arise from ORF4, and including an 
evaluation of the potential toxicity and allergenicity  of these products. Northern blot analysis would WT/DS291/R/Add.6 
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Page H-112 
  
  normally be expected to detect transcription of functional genes, but due to a lack of sensitivity, may 
not detect low abundance messages.  
522. The exquisitely sensitive technique of rever se-transcriptase PCR (RT-PCR) was performed 
and transcription across the nptII gene into ORF4  was detected. However, this result does not 
demonstrate that translation of ORF4 would occu r. As ORF4 lies between the nptII gene and its 
polyadenylation signal, a transcript corresponding to this region of DNA may be expected. Furthermore, the presence of a stop codon immediately following the nptII gene strongly suggests that translation stops at the 3' terminus of this gene. In addition, ORF4 is not in the same codon reading 
frame as the nptII gene and would therefore require a dditional regulatory signals for translation.   
523. Theoretical evaluation of the safety of any translation product from ORF4 is required in the 
assessment. Only the first 50 potential amino aci ds of ORF4 are homologous to the bleomycin 
resistance gene (total of 126 amino acids). This peptide has been shown to have no bleomycin resistance activity.  Therefore, in  the unlikely event of transfer of this putative coding region to micro-
organisms, bleomycin resistance would not be transferred.   
524. Additional bioinformatic analysis would dete rmine if ORF4 has any homology with any 
known protein toxins or allergens. However, given that there are no indications that ORF4 produces a 
protein and that exposure to any proteins from potato clone EH92-527-1 by animals is likely to be extremely low, the transcription of ORF4  does not raise any safety concerns.  
525. Therefore, the additional information requested by the SCP on the potential expression of 
ORF4 would contribute to the validity of the safety  assessment. It should be noted that in seeking 
information from the company, the SCP could have anticipated the need for additional molecular and 
expression analysis data concerning ORF4. For example, sequence analysis of ORF4 to detect any homology with known protein toxins or allergen s was indicated on identification of ORF4.  
9 March 2000 (EC-67/At. 99): the SCP requested Amyl ogene to conduct bioinformatic analysis of the 
amino acid sequence of ORF4 to provide information on the possible allergenicity of any polypeptide 
that might be produced: 
 
The SCP accepts the notifier's evidence that no functional bleomycin resistance protein is 
produced from ORF4. However, the SCP asks the company to provide information on the 
possible allergenicity of any polypeptide that co uld be produced. The SCP accepts that this can 
be completed by comparing sequence homologies using relevant databases. 
 
526. Response :  It is noted above that these data are indicated in this case to assess the safety of 
potato clone EH92-527-1 and therefore in my opi nion were required as part of the dossier. 
20 July 2000 (EC-67/At. 100): the SCP requested Amyl ogene to repeat this analysis to search for 
similarities within ORF4 without any refe rence to the word "allerg" in the query:  
Swiss prot databases have been queried for entrie s with sequence ID's combined with any word 
beginning with "allerg" in any field. For comple teness the SCP asks the notifier for a full search 
for, and list of, similarities within ORF4 with out reference to the word "allerg" in the query. 
 
527. Response:  This second search is unlikely to add any new information to the assessment of 
ORF4 for potential allergenicity. It may, however, identify sequence similarity with known toxins in  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-113 
 
 
  the database, as it appears that this specific informati on had not been supplied to the SCP at this stage. 
This analysis would be consistent with a thorough safety assessment. 
20 July 2000 (EC-67/At. 100): Amylogene was requested to produce antibodies to the ORF4 
polypeptide so as to be able to test for expression in potato clone EH92-527-1. 
 
The SCP thanks the notifier for their efforts in attempting to prepare recombinant polypeptides 
using ORF4 and expression vectors. The notifier is requested to attempt antibody production 
using synthetic polypeptides raised to immunogenic sequences within ORF 4. This should 
include sequences in ORF4 similar to MP12 AMBAR. Several peptides should be prepared 
from sequences spanning components of ORF4 to improve the chance of success. Antibodies 
could be raised in mice, in addition to rabbi ts, to accelerate the process of risk assessment. 
 
528. Response :  Detailed bioinformatic analyses did not indicate homology of the putative ORF4 
amino acid sequence with any known protein toxins or  allergens. Furthermore,  as stated above, there 
is no evidence that ORF4 is translated. Based on the totality of the information on potato clone EH92-
527-1 and its intended uses, sufficient information is available to support the conclusions of the safety 
assessment. Further analysis including Western bl otting requiring ORF4 specific antibodies is not 
justified.  
Between 20 July 2000 and 8 November 2001, the SCP made a number of requests to Amylogene, 
concerning the Western analysis of potato clone EH92-527-1 in relation to expression of ORF4. These 
questions are listed below: 
 
1 February 2001 (EC-67 Attachment 102)  
 
It is necessary to see an alignment of the amino acid sequences used to generate the synthetic 
peptides and the original nucleotide sequence. 
 
In Western blots, figure 1(b), the immunoresponse of the GM leaf protein in lane 12 is very 
different from that of the parent line. In lane 12 two major bands are missing ca 40 and 55kDa, 
yet a band appears to occur between the 40 and 55kDa proteins (ca52kDa?). This band appears 
to be present in lanes 4 and 5 but not in lanes 7,  8, 9, and 11. This implies that expression of 
ORF4 results in the formation of a polypeptide much greater than 17.5 kDa. lane 12 implies that 
this polypeptide and ca 52kDa, resulting from expression of ORF4 in E. coli is in fact presenting 
the GM line. The interpretation of th ese data by the notifier is requested. 
 
Proteins in lane 12 do not appear well resolv ed compared with lanes containing non GM-
derived leaf protein. There is a need to repeat the blots with adequate replication and with 
coumassie stained gels shown in parallel. The notifiers should consider Western blots with 
tubers as well as leaves. 
 
Western blot the purified ORF4 polypeptide from E. coli  not a crude E. coli  extract. 
 
14 March 2001 (EC-67 Attachment 104) 
 
Statements that recombinant ORF4 is a 17.5 kDa protein whereas in the GM plant the 
polypeptide would be 14.4 kDa. Fig 5 indicates that the recombinant protein is >25 kDa? 
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Page H-114 
  
  In Fig 4c a cross reacting band appears at 48 kDa in all lanes with leaf proteins from the GM 
line (lanes 3-9, lane 12) but not in the non GM parent (lane 11). This band cannot represent E. 
coli protein as its intensity does not changes with dilution of the partially purified ORF4. This 
band was commented upon in an earlier question to the notifier (see Fig 1). We also note that 
the Western blot pattern for Fig 1 is significantly different from Fig 4 (with the same samples?) 
 
With respect to dilutions of ORF4 used to "spike" potato protein samples, there appears to be 
very distinct differences in sensitivities for gels in Figs 4 b and d in particular then the presence 
of any ORF4 in tubers may be missed? 
 
The coomassie stained gel shown in Fig 4e (which represents the same samples in each lane 
shown in Fig 4c) indicates that the polypeptide profile in lane 11 (the non  GM parent) is very 
different from the profiles for the GM line. Does this  indicate a lack of substantial equivalence? 
 
The SCP would also like to discuss the numbers and nature of replicate leaf and tuber samples 
chosen and the nature of any additional work th at might be needed to formulate a final risk 
assessment. 
 
3 April 2001 (EC-67 Attachment 105) 
 
The notifier should provide details on the contruct used to express ORF4 in E. coli 
 
Since there is still a question over the ca 48 kDa protein it will be important for the notifier to 
prove their hypothesis that the band is non spec ific and represents an endogenous, naturally 
occurring potato protein. This will mean ca rrying out Western blots with samples from 
equivalent leaf positions using plants of equi valent age and physiological status. Leaves should 
be used from several non GM and GM plants  and experiments for replication purposes. The 
notifier could also include comparisons with other antisense GBSS potato GM lines that 
company might hold to emphasise their argument . Replicated tuber Western blots would also 
be very beneficial. It will be important that the sensitivities of the various Westerns are as 
similar as possible so that any relevant immuno logical cross reactions are not missed. Spiking 
some lanes with ORF4 protein, as done previously, appears to be a good way to approach this. 
In addition to the Western blots, parallel SDS- PAGE and coomassie stained gels of leaves and 
tubers will also allow the SCP to determine eq uivalence of the samples selected in terms of 
overall polypeptide profile.  
 
8 November 2001 (EC-67 Attachment 106) 
 
The SCP requires that all data proceed in response to  questions to notifiers to be of a standard 
acceptable for publication in a well-regarded peer reviewed journal. 
 
The quality of Western blots provided to date and using antibodies raised against ORF 
sequence is not considered adequate. More specifically: 
 
The sensitivity of the detection system appears highly variable from blot to blot for known 
amounts of ORF4 protein. In SDS-PAGE and co omassie stained gels control ORF protein is 
visible in come cases but absent in others. This raised questions on the overall reliability of data 
presented. 
  WT/DS291/R/Add.6 
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 Page H-115 
 
 
  It may be pertinent for the notifier to consider sub-contracting the Western blotting to a third 
party. 
 
The notifier should seriously consider additi onal Western blots using antibodies raised 
specifically against the nptII protein. This will add weight to arguments that the polycistronic 
RNA associated with ORF4 does not give rise to a fusion protein (molecular mass greater than 
that of nptII protein alone). 
 
529. Response :  The totality of the data and analysis  of ORF4 already supplied to the SCP 
supports the validity of the safety assessment without the need for Western blot analysis of ORF4.  
530. APH(3')II (nptII gene product) 
4 February 1999 (EC-67 Attachment 84 Question 6): th e SCP requested that the levels of APH(3')II 
protein be provided for tubers and plant tops: 
 
The concentrations of NPTII protein should be provided for tubers and plant tops (haulms). 
 
531. Response :  A number of countries, including Canada and Australia would usually require this 
information for the safety assessment of a GM plant intended for use as human food. However, the 
guidance document for preparing dossiers (SCP, 1999), states that this information may be required if 
a potential risk is identified.  
532. The nptII gene was used as a selectable marker gene in development of the potato clone 
EH92-527-1 and is expressed in the transgenic potato.  It is generally accepted that information on 
expression levels of novel proteins in GM pl ants are required for the safety assessment.  
533. The nptII gene has been used often as a marker gene in transgenic plants. From previous 
evaluations it has been established that the nptII gene and resistance to kanamycin and neomycin are ubiquitous in nature and that neither the gene nor its protein product pose a risk to human, animal or 
environmental health when used in GM plants. It is therefore unlikely that information on the 
expression levels of nptII in potato clone EH92-527-1 would adversely influence the safety assessment. However, expression levels would be of in terest to determine that patterns of expression 
in the transgenic potato are as expected. Therefore this request is warranted to ensure the safety 
assessment is comprehensive and consistent w ith other regulatory bodi es internationally.  
3 June 1999 (EC-67/at. 85):  In vitro data on the su rvival of the APH(3')II protein from leaf tissue in 
the presence of rumen micro-organisms (and of ORF4, if expressed) was requested by the SCP: 
 
In vitro  data on the survival of nptII protein, preferably supplied as leaf tissue in the presence of 
rumen micro-organisms should be provided. Should ORF4 be expressed and produce a protein 
then the extent of its digestion in the presence of rumen micro-organisms should also be 
determined.  
 
534. Response :  There is concern that horizontal tran sfer of antibiotic resistance genes from 
transgenic plants to gut micro-organisms may cont ribute to increased resistance against clinically 
important antibiotics. The potential impact this may have on human health is assessed on a case-by-
case basis.  WT/DS291/R/Add.6 
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Page H-116 
  
  535. However, as mentioned previously, the nptII gene  is already ubiquitous in nature and has 
been considered by the World Health Organization to pose no additional risk to human or 
environmental health when used in GM plants  (WHO, 1993). Although ORF4 has some homology to 
a bleomycin resistance gene, is not functional a nd therefore would not confer resistance and would 
pose no additional risk if it were to be transferred to micro-organisms in the gut.  
536. Effects on non-target organisms 
4 February 1999 (EC-67/At. 84): the SCP queried why no data were provided on the safety of 
modified crops to non-target organisms: 
No data are provided on the safety of modifi ed crops to non-target organisms. No risk 
assessment has been made. 
 
537. Response :  The nature of this transgenic crop is not such that effects on target organisms 
would be anticipated. Compositional analysis did not identify any changes in the nutrient or 
antinutritional profile of the GM potatoes that w ould suggest concern for non-target organisms. 
Agricultural practises for this crop are identical to  conventional starch potatoes. Amylogene did not 
observe any unusual interaction between the transgen ic potato plants non-target organisms, such as 
insects, during field trials of this crop.  
538. Given this information, further data on the effects of the transgenic potato on non-target 
organisms are not warranted to support a valid safety assessment. 
539. Bleomycin resistance 
3 June 1999 (EC-67/At. 85): the SCP requested cl arification on the potential of ORF4 to provide 
resistance to bleomycin and the possibility of transfer of a functional bleomycin resistance gene to 
non-target organisms: 
 ORF analysis indicates homologies within ORF4 to the bleomycin resistance protein of Tn5. 
Bleomycin is a chemotherapeutic used in cancer treatment. The SCP wishes to know the 
significance of the presence of this ORF… with resp ect to possibilities of transfer of a functional 
bleomycin resistance gene to non-target organism.   
 
540. Response :  The guidance document for the preparation of dossiers (SCP, 1999) and the 
Codex Guideline for the Conduct of Food Safety Assessments of Foods Derived from Recombinant DNA Plants (CAC, 2003) recommend that the safety assessment of GM plants should take into 
account the potential impact of horizontal DNA tran sfer between the plant or plant components and 
micro-organisms.  
541. Therefore, it important to determine whether the potential ORF4 polypeptide would confer 
bleomycin resistance and what impact this would have on human health and the environment if a 
functional bleomycin gene were to be transferred to other organisms,  for example micro-organisms.  
542. Substantial equivalence 
4 February 1999 ( EC-67/Att. 84): the SCP requested additional statistical analysis of the 
compositional data: 
  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-117 
 
 
  Evidence of substantial equivalence: data from 1996 and 1997 should be treated for statistical 
purposes as a single data set and, ideally, strengthened by including data from the 1998 season. 
To fully justify co-variant analysis and conclusi ons derived from it, the interdependence of yield 
and composition should be addressed for two to three growing Seasons 
543. Response :  The SCP guidance document for the preparation of dossiers (SCP, 1999) indicates 
that compositional analyses should be based on samples from at least two growing seasons, with the 
growing sites being diverse in number and locati on, and accompanied by appropriate statistical 
treatment.  The information provided by Amyl ogene indicates that the samples analysed for 
composition purposes were derived from two growing seasons, namely 1996 and 1997.  In each year, 
three trials sites were used. 
544. The SCP guidance document also indicates th at that the specific analyses should be 
appropriate to the crop.  In the case of potatoes, fi ve constituents have been identified as important for 
compositional comparison, namely dr y matter, sugars (especially reduc ing sugars), protein, vitamin C 
and glycoalkaloids (OECD, 2002).  However, several other key c onstituents were also identified 
including starch, fat, fibre, minerals, protease inhibitors and lectins.  Amylogene submitted information on the five constituents recommende d by the OECD Taskforce on Novel Foods and 
Feeds as well as the majority of the other constituents, the notable exceptions being protease inhibitors and lectins. 
545. The results from the compositional analyses indicat e that the majority of the constituents are 
produced in similar levels in the GM and non GM lines.  The levels of three constituents, nitrate, glycoalkaloids and fibre, appear to differ between the two potato varieties in one of the growing seasons only and thus the differences do not appear to be specific to the variety of potato.  The 
analyses also identified several cons tituents that show statistically significant differences between the 
GM and non GM potatoes, including dry matter (may be related to changes in yield), vitamin C and 
sugars.  These differences are consistently observe d over the two growing seasons examined and thus 
appear to be variety specific.   
546. To determine if the differences observed in the le vels of vitamin C and sugars are likely to be 
biologically significant, the levels observed in both potato varieties were compared to the levels of the 
constituents present in the non GM potatoes grown under different environmental conditions.  This 
analysis appears to have been presented for the in formation from the 1996 trial only.  In all cases the 
levels of the three sugars tested and vitamin C fa ll within ranges present in other varieties of potato 
that are readily available.  It is therefore unlikel y that the detected differences in composition pose a 
threat to human health and safety.  Further information from another growing season (ie 1998) is 
therefore not necessary to ensure the validity of the safety assessment. 
547. Amylogene undertook a co-variant analysis on pa rt of the data set, apparently to analyse 
possible effects of the reduced yield on levels of particular constituents.  Given this approach, it is 
reasonable to analyse the data from the two gr owing seasons both as single data sets as well as a 
combined data set.  However, this analysis is not necessary to ensure the validity of the safety 
assessment for the reasons outlined above. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-118 
  
  548. Other Issues 
February1999 EC-67/Att 84 4: the SCP requested information about the fractionated potato products: 
 
Concerning the overall use of the GM plant it would be beneficial to have a fractionation 
scheme showing how by-products arise and the condi tions used for extraction. Relevant analysis 
of each by-product entering the food chain is required .  
 
549. General information on the fractionation of the potato was provided in the original 
application.  The genetically modified potato will be used primarily for starch production. By-
products of starch production are pulp (solid remains of the potato after the st arch has been extracted) 
potato juice (liquid from the potatoes) and potato water (water used to wash the potatoes). The juice and water are used for irrigation and the pulp is used for cattle feed.  The potato and its products are not intended to be used for human food, nor is it intended that the whole tubers be used for animal 
feed.  
550. The safety assessment, addressing the molecular characterisation, properties of any newly 
introduced substances and compositional analysis, h as not identified any health and safety issues 
arising from the genetic modification.  The only co mpositional difference of significance is the type 
of the starch, with the genetically modified potat o having high levels of amylopectin.  However, a 
range of conventional crops produce the amylopectin ty pe of starch (eg maize) and amylopectin type 
starch is also chemically isolated from potatoes.  Ther efore, the safety of this type of starch is well 
established (see also response to questions on Toxicity and animal feeding trials). 
551. The information requested on fractionation of by-products and analysis of the by-products 
entering the food chain was not necessary to support a valid safety assessment. 
552. Overall Conclusion to Question 25:  The SCP was not initially provided with adequate 
information to enable a valid safety assessment to be conducted. However, much of the information 
requested by the SCP would not have had an impa ct on the conclusions of the safety assessment. It 
also should be noted that in seeking information from Amylogene, the SCP could have anticipated much of the data required and requested this from the company in a more timely and coordinated manner.  
553. In conclusion, the totality of the information provided to the SCP up to 20 July 2000 was 
sufficient to enable a valid safet y assessment to be conducted. The information requested after this 
date (and much of the information requested prior to this date) is unlikely to influence the conclusions 
of the safety assessment. 
Dr. Snape  
554. The comments below relate to Question 25 con cerning only the molecular characterisation of 
exhibit EC-067.  These were examined relative to the EFSA-Q-2003-005 guidance document produced by the Scientific Panel on Genetically Modified Organisms. 
555. Exhibit EC-067 :  Potato event EH92-527-1 was produced, using plasmid pHoxwG, by means 
of Agrobacterium-mediated gene transfer . The T-DNA of the plasmid pHoxwG used for 
transformation carries two expression units: one contai ns the potato gbss gene in antisense orientation 
and one contains the nptII antibiotic resistance gene. Potato event EH92-527-1 contains one 
functional transgenic locus containing one copy of the gbss antisense gene. Information relative to the 
molecular characterisation of EH92-527-1 has been found primarily in EC-067 attachments 14, 18,  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-119 
 
 
  20, 21, 36, 37, 39, 41, 42, 43, 44, 60, 82, 107, 108, 111 and 113. A series of comments and questions 
are numbered below. This is followed by a conclusion proposing answers to Question 25: 
556. EC067 – attachment 021:  (1) The southern blot analysis seems to suggest the presence of 
three copies of the gbss promoter (figure 3) and of the gbss gene (figure 8) in wild-type Prevalent potatoes. This contrasts with the results obtained in  figure 6 suggesting that only one copy of the gbss 
gene is present in wild-type Prevalent ( one hybridization signal/band in lane D). 
557. EC067 – attachment 021:  (2) No molecular information is provided on the nptII gene 
integrated into EH92-527-1. This reviewer would suggest to re-probe membranes shown in figure 3,6 
and 8 with an nptII probe.  
558. EC067 – attachment 036:  (3) PCR analysis of the T-DNA integrated into EH92-527-1 
suggests the loss of parts of the left T-DNA seque nce in EH92-527-1. More information would be 
required to characterise the extent of the T-DNA deletion at the left border.  
559. EC067 – attachment 037:  Shows the absence of  transgenic sequence in the chloroplastic 
genome of EH92-527-1 using Southern blot analysis  and "labelled fragments" of the pHoxwG vector 
used as probes.  
560. EC067 – attachment 039:  (4) Shows the absence of vector backbone sequences in EH92-527-
1 using a "probe cocktail" from a ~8000 nt BglII fra gment described in attachment 60.  The use of 
smaller, well defined probes from the backbone (nptIII gene etc…) would have provided more 
accurate information.  
561. EC067 – attachment 041 to 44:  Provides maps and the entire sequence of the pHoxwG vector 
used for potato transformation. 
562. EC067 – attachment 060:  It is mentioned that new experiments will be undertaken to detect 
backbone sequences and to sequence genomic flanking re gions.  (5) This reviewer disagree with the 
following sentence on page 8 of the PDF file "Annex 21 does not give a clear cut case when it comes to unwanted vector sequences in other parts of the genome of EH92-527-1 than associated with the 
inserted integrated DNA". The absence of hybridisa tion signal in the Southern blot hybridisation 
conducted in Annexe 21 (i.e. attachment 39) is  enough to prove that no backbone sequence is 
integrated anywhere in the genome of EH92-527-1 (w ith the limitations associated with the efficacy 
of using a probe cocktail). 
563. EC067 – attachment 86 and 113:  (6) Suggests that the sequencing of genomic flanking 
regions has been performed. This reviewer was una ble to find this information among the attachments 
presented. 
564. EC067 – attachment 111:  (7) This reviewer could not find the molecular analysis showing 
that EH92-527-1  exhibited "genotypic stability" as claimed page 7. Comparative Southern blot 
analysis of primary transformants and plants produ ced through vegetative multiplication is required to 
assess the structural stability of  a transgenic locus.   
565. Conclusion – response to Question 25:  Since the first submission in 1996, the following 
molecular information about EH92-527-1 has been established: 
• EH92-527-1 contains one functional locus c ontaining a single copy of the gbss gene 
in antisense orientation. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-120 
  
  • Some deletion has occurred in the left T-DNA border region. 
• Transgenic sequences outside the T-DNA are unlikely to have been integrated into 
EH92-527-1. 
• Transgenic sequences from pHoxwG are unlikel y to have been integrated into the 
chloroplastic genome.  
566. I would suggest that more information is still required about: 
• The sequence of the transgenic locus especially around the deleted left T-DNA 
region. The proposed architecture of the tr ansgenic locus currently relies only on 
PCR-based studies. 
• The sequence of the flanking plant genomic regions. 
• Additional Southern analysis (using sm all well defined probes) to confirm the 
absence of backbone sequences into the genome. 
• The molecular analysis of plants propa gated vegetatively to demonstrate the 
structural stability of the transgenic lo cus across multiplication cycles. The stability 
of the altered starch composition trait can be used to estimate the genotypic stability 
of the gbss expression unit as only one transgene copy is present in EH92-527-1. 
567. Additional information may have  been submitted to the EC by the company. Experts should 
examine if this information answers so me of the requests formulated above. 
Monsanto Roundup Ready oilseed rape (GT73)  
C/NL/98/11 (EC chronology 70) 
 
Question 26:  Given the information before the Pane l, including the notification (EC-70/At.1-3), 
was the information regarding  molecular charac terization of this product requested by the 
Dutch CA and by the UK (EC-70/At.4, 7, and 8) necessary to ensure that conclusions of the safety assessment were valid?   
Question 27:  Given the information before the Panel, including the notification, was the information regarding feed safety aspects of this product requested by the Netherlands (EC-
70/At.8 and 13) necessary to ensure that conclu sions of the safety assessment were valid? 
Dr. Nutti  
568. Based on the information provided by the applicant in EC-070/At.8 and 13, and the analysis 
done by the EC SCP and according to the Code x Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants (Page 4, paragraph 53), some foods may require additional testing; regarding animal feeding studies, extra studies may be warranted if 
changes in the bioavailability of nutrients are exp ected or if the composition is not comparable to 
conventional foods. Although the prod uct was concluded to be substa ntially equivalent, the notifier 
carried out animal feeding studies with rainbow trout , quail, broilers and lamb. In all these studies, no 
differences were detected among the animals fed conventional and GM oilseed rape based feeds. Therefore, it is concluded that the studies request ed by the Netherlands we re not necessary to ensure 
the product's safety assessment.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-121 
 
 
  Question 28:  Given the information before the Pa nel, including the notification and the SNIF 
(EC-70/At.49-53), was the additional information provided in Monsanto's submission to the 
Commission (EC-70/At.84-97) necessary to ensure that conclusions of the safety assessment 
were valid? 
Dr. Nutti  
569. Based on the information provided by the applicant in EC-070/At.1 to 3, and the analysis 
done by the EC GMO Panel, where it was stated th at GT73 oilseed rape is as safe as conventional 
oilseed rape for humans and animals, and in the context of its proposed use, I concluded that no 
additional experimental studies were necessary, I un derstand that the additional information provided 
by the notifier was not necessary to ensure that conclusions of the safety assessment were valid.  
Dr. Andow  
Necessity of additional information on monitoring plan:  
570. In this answer I will address only the monitori ng issue.  Here the question becomes "is a 
monitoring plan necessary to ensure that conclusions  of the safety assessment were valid?"  The scope 
of the notification is for import and use of GT73,  excluding the cultivation of varieties derived from 
GT73. 
571. The monitoring issues are summarized by the notifier in EC-70/At.85. 
6. Monitoring 
AUSTRIA:  The scenarios set out at point 2.3 and the properties of rapeseed oil also 
facilitate the appearance of the product in various conventional rapeseed oil 
cultivation areas or adjacent locations, even though probably only as a small proportion.  Nevertheless, this fact must be accordingly taken into account by 
consideration in a monitoring programme in accordance with appendix VII f the 
guideline 2001/18/EG.  However, this is not allowed for on the part of the applicant 
(cf. test report by the competent Dutch authorities).  
DENMARK:  The monitoring plan should incl ude observation on dispersal and gene 
transfer to oilseed rape and wild relatives.  
ITALY:  The company shall not only indicate the main places of entrances in each 
country but also the storage location and the wa y of the transport;  this is due to the 
need of guarantee an efficient monitoring plan.  In any case the processing plants 
should be nearby the places of entrance and every measure to avoid the dispersal of 
grains into the environment must be ensured.  
SPAIN:  The current scope of this application fo r consent to place GT73 oilseed rape 
on the market includes both import and processing in the European Union, excluding cultivation.  Nevertheless, assuming that an unintentional release could be raised, the 
Spanish Competent Authority considers that a post-market monitoring plan is needed to consider this aspect.  The monitoring plan should include sampling in order to carry out studies on transgene expression on wild relatives, conventional oil seed rape crops, volunteers growing across th e transit way during import and processing.  WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-122 
  
  UK:  The UK requests to monitor for the presence of feral GT 73 oilseed rape at the 
points of import and processing, and betw een those locations and proposes to 
establish an action plan should feral GT73 be identified …  The proposal for post-
market monitoring is not adequate.  As outlined above, the environmental risk 
assessment assumes that seed will not be spilled, so the post market monitoring plan 
should test this assumption.  The UK requests that the applicant gives further consideration to the post-market monito ring plan, which should include (i) 
monitoring for the presence of feral GT73 oilseed rape at the points of import and 
processing, and between those locations;  and, (ii) proposals for action should feral 
GT73 be identified.
93
572. The full context for understanding Austria's concerns is provided in EC-70/At.77, 25 March 
2003, Objections raised by Austria, and is reproduced below.  Austria is concerned about accidental release during transport or processing and subseque nt invasion of other agricultural systems. 
• 2.3 Ecology : Importing the product for processing and use for food and animal feed is 
no guarantee that GT73 will not be released  into the environment. Experiences and 
checks in Austria during the last few growing seasons have shown that genetically modified seeds can come into circulation as a result of accidental or technically unavoidable contamination (e.g. in the transport or processing stage). In the case of oilseed rape, with its specific characteristics (ability to survive, potential for dispersal 
and outcrossing), there is a possibility of it spreading into agricultural ecosystems. 
573. This could therefore affect the possibilities fo r coexistence between different agricultural 
production systems with and without GMOs. The pr oduct cannot be approved until there is EU-wide 
clarification of the possibilities for coexistence and a legally binding framework (e.g. specifying 
threshold values) has been defined. 
574. The full context for understanding Italy's concer ns is provided in EC-70/At.71, 24 March 
2003, Objections raised by Italy.  Italy requests monitoring to provide a means for managing risks associated with AMPA. 
2) As for the previous notification C/ES/00/01, there is an extensive discussion of possible effects on animal and human health (due to antinutrictional factors), but there is no data on the possible content of gliphosate and/or metabolites (AMPA).  In 
this regard, we note that event GT73 contains a gene specific for the degradation of 
gliphosate into AMPA, but see no discussion of the possible consequences.
94
575. The Spanish CA expands on their concerns in EC-70/At.75, 25 March 2003, Request for 
additional data from Spain.  Spain is concerne d about accidental releases during transport or 
processing. 
Specific actions to avoid unintended dispersal 
The Company should strengthen the operating procedures to ensure that seeds are not 
spilled during transport and processing.  These requirements should be included in the 
consent of the product. 
                                                      
93 Page 25.  This and all other page references to EC documents in the answer refer to the page of the 
pdf file. 
94 Page 1.  WT/DS291/R/Add.6 
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  576. The full context of the concerns of the UK are given in EC-70/At.74, 25 March 2003, Request 
for additional data from UK.  The UK is concerne d about accidental release and suggests that the 
monitoring plan test the assumption that there will be no spillage, either during importation, transport 
or processing. 
2. Procedures to avoid seed spill .  A central argument used in the environmental 
risk assessment of this GMO is the assumpti on that the rape seeds will not be released 
into the environment.  However, if there is spillage of seed between import and 
processing this may lead to the presence of transient populations of feral GT73 
oilseed rape.  The UK requests further details fr om the applicant concerning the 
standard operating procedures that will be used to ensure that seed is not spilled during transit.   Acceptable procedures to minimize seed spill should be a condition 
of any consent issued – this could restrict import and processing to specific locations 
and require monitoring for seed spill between  the sites of import and processing (see 
below).
95
5. Post-market monitoring plan .  The proposal for post-market monitoring is not 
adequate.  As outlined above, the envir onmental risk assessment assumes that seed 
will not be spilled, so the post-market monitoring plan should test this assumption.  
The UK requests that the applicant giv es further consideration to the post-
market monitoring plan, which should in clude (i) monitoring for the presence of 
feral GT73 oilseed rape at the points of import and processing, and between 
those locations; and, (ii) proposals for action should feral GT73 be identified.   
The proposal for post-market monitoring also  includes a request to end users of GT73 
grain to inform the regulatory authorities of any adverse effects that are attributable to 
the use of the GMO.  The UK considers that the applicant should be more proactive 
in obtaining this information and should be  combined with a reporting requirement.  
The UK requests that the consent holder approach end users directly to ask if 
they have observed any effects to cov er general surveillance and the results of 
this should be reported to the competent authorities at intervals of 6 months for 
the first 3 years of the consent.   The report should list the requests that have been 
made to end users, the proportion that elic it a response and what, if any, unexpected 
effects were observed (adverse or otherwise).96
577. These concerns of the UK were initially articulated by the scientific Advisory Committee on 
Releases to the Environment (ACRE) in EC-70/At .69, 10 March 2003, ACRE Advice to the Secretary 
of State for Environment, Food and Rural Affairs, Scottish Ministers, Ministers of the Welsh 
Assembly Government and the Department of En vironment (Northern Ireland).  Their advice and 
reasoning is repeated here. 
Primary Advice:   
• 3. The post market monitoring plan should include monitoring for spillage of GT73 seed during import, transportation and processing and test for the establishment of feral populations of GT73 oilseed rape.  The plan should also include appropriate emergency plans should such populations be identified. 
 
                                                      
95 Page 2. 
96 Page 2. WT/DS291/R/Add.6 
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Page H-124 
  
  Post market monitoring plan : 
• The post market monitoring plan is a new requirement under Directive 2001/18/EC.  
The plan provided by the notifier is brief and limited.  On the basis of the risk 
assessment for GT73 Monsanto do not propose to carry out any case-specific 
monitoring.  ACRE agree with this conclusion as the risk assessment does not identify any risks in relation to human h ealth or the environment from the use of 
GT73 oilseed rape as defined in the notif ication (i.e. for import and processing). 
• Directive 2001/18/EC places a requirement to provide a monitoring plan for the occurrence of adverse effects not anticipated  in the environmental risk assessment.  
ACRE consider that the proposal in respon se to this requirement put forward by the 
notifier is unsatisfactory.  In particular the plan does not take into account monitoring of the occurrence and effects of seed spill during transportation and processing of the 
oilseed rape seed.  Based on current experience regarding movement of non-GM oilseed rape in the UK seed spill is likely to  occur and will result in the survival and 
establishment of feral oilseed rape populati ons and their hybridisation with crop and 
other feral populations.  It is accepted that the risk of harm to human health and the 
environment from seed spill is low, however there is an issue, in the UK, regarding 
the segregation of transgenic and non-transgen ic material.  Hence, ACRE request that 
Monsanto review their monitoring plan taking into account methods of monitoring and reporting seed spill, incorporating a proposal as to how seed spill may be 
controlled.  It should also include plans for monitoring and controlling establishment 
of feral populations as a result of seed spill. 
578. In addition, Sweden raised a monitoring issu es in EC-70/At.67, 28 February 2003, Swedish 
Board of Agriculture, which is repeated below.  Sweden has focused on procedures to report adverse effects. 
A. Monitoring plan 
1. The monitoring focuses on the identifi cation, checking and traceability of GT73, 
whereby Monsanto Europe is to: 
• pass information to the traders and users w ithin the processing industries in order for 
them to be able to identify any negative effects on the environment or on human health and request these users to info rm the Competent Authorities about any 
identified negative effects on the environment or human health which are assumed to 
have come about from the use of GT73, 
• to inform the European food industries dir ectly when the product has been approved 
and to request operators in food chains to inform the Competent Authorities about 
any identified negative effects on the health of  animals, which are reported to them by 
farmers or other users, and which are assumed to have come about from the use of GT73, 
• immediately inform the Commission and Competent Authorities during the consent 
period if the company receives information about negative effects of the product.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-125 
 
 
                                                       579. Moreover, although Norway is not a part of the EC, Norway submitted comments related to 
monitoring in EC70/At.78, 25 March 2003, Comments from Norway.  Norway merely notes that there 
should be a monitoring plan. 
Although required according to Directive 200 1/18/EC, there is no monitoring plan 
attached to the application.  The Competent Authority of the Netherlands 
recommends an approval on the condition that the notifier gives a yearly report of the 
sold quantities of line GT73 in each count ry.  We will comment on the need for 
additional monitoring when we have finished our assessment of the risks for human 
health and the environment. 
580. Notwithstanding that a monitoring plan is required by Directive 2001/18/EC, it is still 
possible to consider if a monitoring  plan is necessary from a scientific standpoint, and if so, what kind 
of monitoring plan could appropriately address the potential risks. 
581. Before doing so, I will establish that in th e SNIF to COM on 16 January 2003, the notifier 
proposed a plan that must be considered a case-sp ecific monitoring plan.  This is a critical step, 
because had the notifier not proposed such a monito ring plan, then the issue would hinge on whether 
any monitoring plan is needed.  Instead, the i ssue will hinge on the adequacy of the proposed 
monitoring plan.  This is a substantially more complex argument. 
582. In EC-70/At.54 (16 January 20 03 SNIF), the notifier states that unintended release can occur 
during import, transport and processing.  The notifier suggests that because most grain is crushed near seaports and modern equipment is used that  there is little chance of unintended release. 
7. Measures suggested by the notifier to  take in case of unintended release or 
misuse as well as measures for disposal and treatment 
This application is for consent for import and use in the EU of GT73 as any other 
OSR, but do not include the cultivation of varieties in the E.U.  Therefore an 
unintended release would be more likely to occur during import, processing and 
transportation of GT73 grain.  However, most OSR grain imported into the E.U. via European sea ports is immediately crushed in nearby crushing facilities and modern 
methods of transportation and grain handling minimize losses of grain.  Therefore, 
there is little chance of germination of grai n resulting in the development of mature 
plants of GT73 in the E.U. environment. 
GT73 is intended for use by oilseed producers, in the same manner as other oilseed rape varieties.  The measures for waste disposal and treatment for GT73 products are the same as those for other oilseed rape products.
97
583. In EC-70/At.54 (16 January 2003 SNIF), the notifier argues that there is no need for post-
release monitoring.  First, two years of monitori ng volunteers in Canada and the US indicated that 
there were no greater numbers of volunteers than  non-transgenic rape and that the transgenic 
volunteers could be controlled by other herbicides.  Second no adverse effects of GT73 have been identified.   
584. Previous commercializations of GT73 have been alongside a stewardship program, which 
provides a communication channel if an unan ticipated adverse effect would occur. 
 
97 Page 5. WT/DS291/R/Add.6 
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                                                       (f) Aim of post-releases monitoring 
In the case of the field testing performed in Canada and the US, the fields were 
monitored for volunteers during a period of tw o years and volunteers were chemically 
removed. 
Since no adverse effects of GT73 have been identified (see section 29), no 
requirement for case-specific post-release monitoring is indicated, which is consistent with approvals granted in other world areas. 
GT73 has been commercialized alongs ide stewardship programmes involving 
downstream stakeholders in the use of this  oilseed rape, in order to ensure the 
implementation of good agricultural practice in its cultivation and a channel of communication in the unlikely event that una nticipated adverse effects might occur. 
(g) Duration of post-releases monitoring 
In the case of the field testing performed in Canada and the US, the fields were 
monitored for volunteers during a period of two years. 
(h) Conclusions of post-release monitoring 
The monitoring conducted after the Canadian and US field releases showed no 
differences in volunteer numbers between GT73 and conventional OSR varieties in the number of volunteers, and confirmed that GT73 volunteers can be effectively controlled.  No unanticipated effects have  been observed since the commercialization 
of GT73 in other world areas, nor during th e many years of field-testing inside and 
outside the E.U.
98
585. In EC-70/At.54 (16 January 2003 SNIF), the notif ier indicates that the monitoring plan will 
focus on general surveillance for unanticipated adverse effects. 
D. INFORMATION RELATING TO THE MONITORING PLAN-
IDENTIFIED TRAITS, CHARACTERI STICS AND UNCERTAINTIES RELATED 
TO THE GMO OR ITS INTERACTION WITH THE ENVIRONMENT THAT 
SHOULD BE ADDRESSED IN THE POST COMMERCIALISATION MONITORING PLAN 
2. Identification of the occurrence of adverse effects of the GMO or its use on human health or the environment which were not anticipated in the E.R.A. 
The environmental and human health safety  assessment for GT73 did not identify any 
specific risks related to its placing on the market during storage, processing and other uses.  Therefore the monitoring plan for GT73 is focused on general surveillance for unanticipated, adverse effects.
99
 
98 Page 19. 
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                                                       586. In EC-70/At.55 (16 January 20 03 SNIF), the notifier indicates that there will be no special 
measures taken to prevent escape or misuse of the product nor will th ere be any specific instructions 
or recommendation for storage or handling. 
Part II. Additional Relevant Information 
5. The measures to be taken in the ev ent of the escape of the organisms in the 
product or misuse of the product. 
GTOSR is targeted for use by oilseed producers, in the same manner as other OSR 
varieties.  Dissemination of OSR plants in to non-agricultural environments, such as 
roadsides and other semi-managed areas, occurs currently.  The information 
presented in this application establishes that the frequency of dissemination of GTOSR will be similar to other OSR, a nd no special measures will be taken to 
prevent dissemination. 
6. Specific instructions or recommendations for storage and handling of the 
product. 
Since GTOSR varieties have b een demonstrated to be s ubstantially equivalent to 
other OSR varieties, apart from their tolera nce to glyphosate, no specific instructions 
or recommendations for storage and handling are envisaged.100
587. Lastly, the notifier submitted with the 13 December 2002 notification to the Netherlands CA 
an Annex VII, Monitoring Plan (EC-70/At.51) in wh ich they propose that no case-specific monitoring 
is needed.   
588. However, in the same appendix they pro pose three measures to identify potential 
unanticipated adverse effects.  All three measures are specific to GT73, so these measures must be 
considered a proposal for case-specific monitoring, even if the notifier and ACRE (paragraph 577) do 
not recognize them as such.  The specifics of this proposal follow.  It should be clear that although 
this proposal parallels the concerns of Sweden (paragraph 578), it is substantially different. 
2. Identification of the occurrence of adve rse effects of the GMO or its use on human 
health or the environment which we re not anticipated in the e.r.a. 
Since the notification of GT73 oilseed rape is for consent for import only, and since the 
majority of use of this oilseed rape will be for human and animal consumption (see Annex IV, 
A.4.), it follows that unanticipated affects are most likely to be manifested as a result of this 
use. Therefore, it is proposed:  
• To provide traders and processors of bulk mixtures of oilseed rape grain, likely to 
contain GT73 oilseed rape grain, with pr oduct information about GT73 oilseed rape 
grain. Traders and processors will be request ed to inform the relevant authorities of 
any adverse effects on the environment or human health, which they consider to be attributable to GT73 oilseed rape grain.  
• To inform the European feed industry directly, by way of a public announcement, of the consent for placing on the market of GT73 oilseed rape at such time as it appears 
 
100 Page 66. WT/DS291/R/Add.6 
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                                                       in the Official Journal of the rapporteur Member State. Monsanto will also offer to 
meet with interested operators to discuss the safety and general characteristics of the 
product. Operators in the feed chain will be requested to inform the relevant 
authorities of any adverse effects on animal  health reported to them through farmers 
or national feed associations, which they consid er to be attributable to the feed use of 
GT73 oilseed rape grain.  
• For the duration of the authorization of GT73 oilseed rape, to immediately inform the 
Commission and the Competent Authorities for Directive 2001/18/EC, of any reports of adverse effects, which come to the atte ntion of Monsanto, so that any reports can 
be further investigated by the appropriate authorities. 
589. Although it may be true that the notifier made a similar monitoring proposal in the 16 January 
2003 SNIF, I could not find this clearly stated in the SNIF.  However, under the assumption that any item in the notification to a country CA is automatic ally a part of the submission to the COM, it must 
be concluded that there was a case-specific monitoring plan proposed in the 16 January 2003 
SNIF.  
590. Are the additional requests made by the memb er nations regarding the monitoring plan 
necessary to ensure that conclusions of the safety assessment were valid?  To argue this question, I 
will first consider if concerns over inadvertent esc ape are valid, then consider if there are valid 
reasons for distinguishing GT73 from other rape vari eties, then discuss the ad equacy of the proposed 
case-specific monitoring plan, and finally I will addr ess the specific monitoring advice provided by 
the various member countries.  In addition, I will consider if there was any change in the proposed 
monitoring plan, based on an examination of th e new information submitted by the notifier on 
5 August 2003 (EC-70/At.92). 
591. Concerns that rape seed can escape during import, transport or processing are valid.  This was 
first brought to scientific attention for rape seed in 1995 in the UK.101  Moreover, using standard 
modern equipment, it is simply not possible to ensu re that spillage will not occur.  The concerns of 
Denmark (paragraph 571), Austria (paragraph 572), Spain (paragraph 575) and the UK 
(paragraph 576) begin with this concern. 
592. Should transgenic GT73 be distinguished from conve ntional rape varieties?  Here the various 
countries express different perspectives.  Denmark (paragraph 571), Spain (paragraph 575), the UK 
(paragraph 576) and Norway (paragraph 579) do not link their request for additional monitoring to a 
specific risk.  Austria is concerned about potential contamination of other agricultural systems with 
undesired transgenes (paragraph 572), Italy is concerned about potential effects of glyphosate 
metabolites (paragraph 574), and Sweden is concerned that a monitoring system is set up so that 
adverse effects, should they occu r, can be identified (paragraph 578).  In addition, the UK (paragraphs 
576 and 577) suggests that monitoring should test the assumption of the notifier that seed will not be 
spilled. 
593. Without a connection to a specific risk or th e risk assessment, requests for monitoring GT73 
cannot be distinguished from conventional rape varie ties, and the requests and concerns of Denmark, 
Spain and Norway cannot be scientifically justifie d on the basis of the written record received.  
Austria's specific concern and the reasoning behi nd the UK requests are scientifically justified, and 
both would require that GT73 is distinguished from conventional rape varieties.  I was unable to 
 
101 Crawley, M.J. & Brown, S.L.  (1995). Seed limitation and the dynamics of oilseed rape on the M25 
motorway.  Proc. R. Soc. Ser. B.-Bio, 259, 49-54.  WT/DS291/R/Add.6 
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                                                       determine if Italy's concern had been treated in the notification (13 December 2002) or the SNIF (16 
January 2003).  If it has not been adequately assessed, then Italy's concern is scientifically justified, and would distinguish GT73 both from conventi onal rape varieties and from glyphosate itself 
(because the plant metabolite AMPA would be less of  a concern on non-GMHT oilseed rape crops).  
Sweden's concern is that the monitoring plan be su fficient to identify unanticipated adverse effects. 
594. Adequacy of proposed case-specific monitoring plan (EC-70/At.51, Annex VII, Monitoring 
Plan).  The test for adequacy is whether the propo sed plan would meet the aims proposed by Sweden, 
Austria, the UK and Italy.  The first measure (paragraph 587)102 partially meets Sweden's concern, but 
does not address the concerns of Austria, th e UK or Italy.  The second measure (paragraph 587)103 
meets none of these countries concerns.  The third measure (paragraph 587)104 partially meets 
Sweden's concern, but does not address the concerns of Austria, the UK or Italy.  Thus the proposed 
monitoring plan does not meet the concerns of the Sweden, Austria, the UK or Italy. 
595. Specific monitoring advice from the member countries is incomplete and too inflexible.  By 
incomplete, I refer to the criteria for monitoring in my response to question 24a.  By inflexible I refer 
to the recommendations that the notifier monitor rapeseed cultivation areas, gene dispersal, gene transfer, studies on transgene expression in wild relatives and conventional oil seed rape crops, and 
sampling of volunteers.  Meeting the concerns of Sweden, Austria, the UK and Italy do not require such an intensive monitoring plan.  A general prin ciple of GMO risk assessment is that risk is 
proportional to the scale of release.
105  Low frequency releases at sma ll spatial scales will have lower 
risk, and the monitoring system should reflect this.   
596. The revised monitoring plan (5 August 2003, EC-70/At.92, Appendix 9)106 falls well short of 
the meeting the concerns expressed by Sweden, Austri a, the UK and Italy, and meets even fewer of 
the criteria for an adequate monitoring plan that the original proposal (13 December 2002, EC-70/At.51).   
597. In EC-70/At.85, the notifier makes an effective argument107 that grain entering the main 
gateways and crushed in the port areas is very un likely to establish in the environment.  Hence it 
could be suggested that the concerns of Austria, the UK and Italy could best be met by concentrating 
monitoring activities in places other than these main gateways and crushing facilities, focusing on those for which escape may be more likely (worst cases).  By monitoring a few potential worst cases, 
 
102 To provide traders and processors of bulk mixtures of oilseed rape grain, likely to contain GT73 
oilseed rape grain, with product information about GT73  oilseed rape grain. Traders and processors will be 
requested to inform the relevant authorities of any adverse effects on the environment or human health, which 
they consider to be attributable to GT73 oilseed rape grain. 
103 To inform the European feed industry directly, by  way of a public announcement, of the consent for 
placing on the market of GT73 oilseed rape at such time as it appears in the Official  Journal of the rapporteur 
Member State. Monsanto will also o ffer to meet with interested operators to discuss the safety and general 
characteristics of the product. Operators in the feed chain will be requested to inform the relevant authorities of 
any adverse effects on animal health reported to them through farmers or national feed associations, which they 
consider to be attributable to the f eed use of GT73 oilseed rape grain. 
104 For the duration of the authorization of GT73 oilseed rape, to immediately inform the Commission 
and the Competent Authorities for Directive 2001/18/EC, of  any reports of adverse effects, which come to the 
attention of Monsanto, so that any reports can be further investigated by the appropriate authorities. 
105 NRC (National Research  Council).  (1987).  Introduction of recombinant DNA-engineered 
organisms into the environment: key issues.   National Academy Press, Washington, DC. 
106 Pages 17-26. 
107 Page 26. WT/DS291/R/Add.6 
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  it can be argued that all other cases are likely to ha ve even lower risk.  Th e suggestions by Sweden 
(paragraph 578) have not been addressed yet. 
598. Monitoring is a form of risk management, and might be argued to be independent of the risk 
assessment process.  However, in this specific case, issues associated with monitoring are intricately 
tied to the issues associated with risk assessment, in that the risks associat ed with unanticipated 
possible hazards can be reduced to acceptable leve ls with the appropriate monitoring plan, as 
suggested by Sweden.  For GT73,  specific concerns include contamination of other agricultural 
systems and possible effects of glyphosate metabolites.   Moreover, monitoring can be used to confirm 
critical assumptions in the risk assessment (Annex VII, Directive 2001/18/EC), which is suggested by 
the UK for this case.  Hence, from these perspectives, it can be concluded that a monitoring plan is 
necessary to ensure that conclusions of the safety assessment were valid.   However, the 
monitoring plans advised by the countries are on ba lance overly specific and do not allow the notifier 
sufficient latitude to suggest alternative approaches that would address the concerns in ways that may 
be more cost-effective. 
599. The Member States requested information related to  the monitoring plan on 28 February 2003 
(Sweden) and 24/25 March 2003 (Austria, Italy, Sp ain, United Kingdom.  I have assumed that the 
monitoring plan was submitted to COM with the SN IF on 16 January 2003.  The earliest date of 
submission of this plan was 13 December 2002.  Usi ng the later date, it took the Member State 43-68 
days to respond with comments.  Using the earli er date, this would be 77-102 days to respond 
(including the winter holidays).  These do not seem to be unreasonable lengths of time for a response. 
Bayer Liberty Link oilseed rape (T45 & Topas 19/2)  
C/GB/99/M5/2 (EC chronology 72) 
Question 29:  Given the information before the Pa nel, including the notification (EC-72/At.1-3) 
and additional information provided by AgrE vro (EC-72/At.7-9), were requests for more 
information (EC-72/At.5, 6, and 11-13) concerning feeding studies, chemical compositional data 
and potential interactions of transformation ev ents in the stacked product necessary to ensure 
that conclusions of the safety assessment were valid? 
Dr. Nutti  
600. Based on the information provided by the applicant in EC-72/1-3 and additional information 
at EC-72/At.7-9 and the minutes of the Sixty-Seco nd Meeting of ACRE, when it was verified that 
there were a number of inconsistencies in the mo lecular data provided and the dossier was rather 
impenetrable. Also, too much important material was buried in annexes rather than being in the core 
dossier and the descriptions of the plasmid maps and analyses did not correspond with the data as 
presented. Further concerns were expressed about de ficiencies in the molecular studies carried out to 
characterize the inserted DNA, although it was accepte d that the appropriate experimental data may 
have been supplied somewhere in the notification dossier but it was not immediately obvious where it 
might be. Therefore, I understand that ACRE and the UK SC requests for more information were 
necessary to ensure that conclusions of the safety assessment were valid. It is important to point out 
that ACRE was not being asked for formal advi ce at that stage, only guidance; therefore, no 
conclusions were drawn at the time.   WT/DS291/R/Add.6 
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  Stoneville BXN cotton (10215, 10222, 10224) (formerly held by Aventis and Calgene)  
C/ES/99/01 (EC chronology 73) 
 
Question 30:  Given the information before the Panel, including the notification (EC-73/At.1), 
was additional information regarding environmenta l impact tests, feed safety, residue analysis, 
monitoring for herbicide resistance requested by Spain (EC-73/At.3) necessary to ensure that 
conclusions of the safety assessment were valid? 
Dr. Nutti  
601. This question could not be properly answered because the complete notification was not made 
available to me (At. 1 corresponds to the notific ation index only). However, the answers to the 
questions, which are presented in At.4, seem to be  satisfactory as far as food safety is concerned 
(question 7). Nevertheless, the entire evaluation pro cess is, by the chronology made available, at its 
initial stage, so conclusions on the validit y of the safety assessment cannot be drawn. 
Dr. Andow  
Necessity to ensure validity of safety assessment  
602. I will address items 8, 9 and 11 as listed in EC -73/At.03 (15 July 1999, proposed amendments 
to 3 May 1999 notification made by lead CA).  These relate to environmental impact tests, herbicide 
studies, and resistance evolution.  The issue is to determine if this additional information is necessary to ensure valid conclusions of the safety assessment. 
8. The results concerning the environmental impact of these genetically modified plants refer almost exclusively to studies conducted in the USA, Japan, Argentina, etc. (page 37).  The results of  tests conducted in Spain and Greece should 
also be included, considering that in some cases the environmental conditions cannot be extrapolated. 
9. Indicate where and when the survival  study described on page 38 was carried 
out.  These studies were conducted on two lines other than the lines covered by this application. 
11. Provide toxicological and ecotoxicological studies on the herbicide used on this type of crop. 
13. As regards points 11 and 12, the results of the studies must be indicated as a 
function of the different doses of product applied, as was the case in various 
phonological studies on cotton plants. 
In addition to clarification of these points, the National Biosafety Committee considered that the company should pr opose specific methods for management, 
monitoring and handling of this crop in order to reduce the possibility that resistance 
to this herbicide could emerge. 
603. Similar concerns are reiterated in EC-73/At. 12, the 26 September 2003, analysis of the 16 
January 2003 notification by the Spanish NCB. WT/DS291/R/Add.6 
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  604. The full text of the original notification is not available.  EC-73/At.01 contains only the table 
of contents of the full notification submitted to th e Spanish CA on 3 May 1999.  From an examination 
of the appropriate parts of this table of contents (below), I conclude that no environmental impact 
studies were reported, no herbicide or residue toxi city or ecotoxicity tests were reported, and no 
proposal to manage, monitor and handle the crop to reduce the risk of herbic ide resistance in weeds 
was made.  There are no headings in the table of cont ents for some of these topics, and the number of 
pages that could be devoted to these topics is <2 pages. 
 D.7.e)  Impacto medioambiental de las líneas de algodón OXY    78 
 
 i.  interacciones de las líneas de algodón OXY con el ambiente    78 
 
 ii.  impacto medioambiental del OMG(s)      78 
 
 D.8.  Interacciones potencialmente significativas con organismos  
 no modificados          7 9  
 
 D.9.  Descripción de las técnicas de detección e identificación de la  
 planta modificada geneticamente       7 9  
 
 D.9.a)  Descripción de las técnicas de detección del OMG en el ambiente  79 
 
 i.  detección fenotipica         79 
 
 ii  detección molecular         79 
 
 D.9.b)  Descripción de las técnicas de identificación     79 
 
 D.10.  Información sobre liberaciones p revias de la planta modificada 
 geneticamente           7 9  
 
 H.  INFORMACIÓN SOBRE EL POTENCIAL DE IMPACTO  
 MEDIOAMBIENTAL DE LA LIBERACIÓN DE PLANTAS  
 MODIFICADAS GENETICAMENTE       80 
 
 H.1.  Probabilidad de que el OMG devenga más resistente que la planta  
 receptora o parental en los habitats agríc olas o más agresiva en los habitats  
 naturals         80 
 
 H.1.a)  Potencial de convertirse en malas hierbas     80 
 
 H.1.b)  Resultados de germinaci ón y vigor de las líneas de algodón OXY  
 y Coker 315          80 
 
 H.1.c)  Potencial de cruzamiento externo      80 
 
 H.1.d)  Susceptibilidad del algodón OXY a enfermedades comunes del algodón  80 
 
605. The full text of the SNIF (19 March 2003) and the updated notification (15 January 2003) are 
not available in the materials provided.  WT/DS291/R/Add.6 
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                                                       606. This requires me to assume that the issues noted  in 30.01 were not addressed in any of the 
submissions by the notifier, and to answer the ques tion without reference to the specifics of the case.  
607. Environmental impacts.  Data from the US, Japan , Argentina, etc on page 37 of the original 
notification must refer to cotton reproduction and se ed and pollen dispersal rather than environmental 
impacts.  The table of contents indicates that page 37 addresses these topics, not environmental 
impacts.  Some data on environmental impacts is n eeded to support a scientific finding of safety.  It 
must be concluded that the request for environm ental impact tests is necessary to ensure that 
conclusions of the safety assessment are valid.  How much testing is necessary, however, is not 
addressed by this conclusion. 
608. In the hypothetical, we can suppose that environmental impact data from US, Japan, 
Argentina, etc. were available and presented as data , rather than summary conclusions.  Would this be 
sufficient to meet the needs for completing a scientif ically valid assessment of environmental impact?  
In other words, is it necessary to have local data  from Greece and Spain to complete a scientifically 
valid assessment of environmental impact?  In gene ral, this would be difficult to answer in the 
abstract, because depending on the impact being assessed, it may be possible to generalize across 
continents.  For example, a species that is invasive  in one location, such as Monterey pine in South 
Africa or the seaweed caulerpa in the Mediterranean Sea, is predicted to be invasive in all other parts 
of the world with similar climate.  For transgenic crops, however, this can be answered in general, at 
least up to and including the present time (Janua ry 2005).  There is still not enough scientific 
information to know how environmental impact of transgenic crops genera lizes across continents.  
Indeed, the commitment to case-specif ic risk assessment is made because it is not yet clear how to 
generalize across crop, transgene, or receiving envi ronment when it concerns environmental risk.  
Hence, it must be concluded in the hypothetical that the request for environmental impact tests 
conducted in relevant environments in EC countri es is necessary to ensure that conclusions of the 
safety assessment are valid.  Again, the question of how much testing is necessary is not addressed by 
this conclusion. 
609. Herbicide and residue toxicity and ecotoxicity.  Many of these issues may have already been 
addressed during the process of registering the herbic ide for use on the untransformed crop.  An issue 
that may not have been addressed in during herbicide registration concerns plant-specific herbicide metabolites.  Thus, it is possible to conclude that  the request for herbicide residue analysis is 
necessary to ensure that conclusions of the safety assessment are valid.  However, it is also possible that this information is already available under pesticide registration laws, in which case, it may not be necessary. 
610. Weed resistance risk, management and monitoring.  I addressed this issue at some length in 
my response to question 24.  The same argument holds here.  Common groundsel (Senecio vulgaris) 
in Oregon is resistant to bromoxinil.108  This is a common weed in Europe.  The risk of resistance is 
real.  It must be concluded that the request fo r monitoring for herbicide resistance is necessary to 
ensure that conclusions of the safety assessment are valid.  Once again, however, this does not address 
the question of how much information on herbicide resistance is necessary. 
611. I conclude that the additional information regarding environmental impact tests and 
monitoring for herbicide resistance requested by Spain (EC-73/At.3) is scientifically justified 
and necessary to ensure that conclusion s of the safety assessment are valid.   The requested 
information on residue analysis may be valid, or it may not be necessary (paragraph 609).  However, 
 
108 This is the only case of resistance to bromoxynil reported to date, www.weedscience.org , last 
accessed 22 December 2004.  http://www.weedscience.org/Case/Case.asp?ResistID=322 .   WT/DS291/R/Add.6 
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  these conclusions do not address how much additional information would be necessary.  Given the 
information before the Panel this qua ntitative issue cannot be addressed.  
612. The information requested by Spain was on 15 Ju ly 1999 to material submitted by the notifier 
on 3 May 1999.  This was 73 days to res pond.  This does not seem unreasonably long. 
Question 31:  Given the information before the Panel, including the notification  and the 
notifier's responses to questions (EC-73/At.2), was additional information regarding feed safety 
and compositional analysis (particularly related to nitrilase levels) (EC-73/At.3) necessary to 
ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
613. Once again, this question could not be prope rly answered either, since the complete 
notification was not made available to me (At.1 co rresponds to the notification index only). However, 
the answer to question 7 (nitrilase le vel in cottonseed oil) seems to be satisfactory. Also in this case, 
the entire evaluation process is, by the chronology made  available, at its initial stage, so conclusions 
on the validity of the safety assessment cannot be drawn. 
Pioneer/Dow AgroSciences Bt corn Cry1F (1507)  
C/NL/00/10 (EC chronology 74) 
 
Question 32:  Given the information before the Pa nel, including the original notification (EC-
74/At.1-15), was the information regarding molecula r characterization of this product requested 
by the lead CA (EC-74/At.17 and 33) necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
614. Based on the information provided by the appli cant (EC-074/At. 01-15) and the request by the 
lead CA (EC-074/At.17), I can conclude that a lot of information was provided. 
However, I do not feel capable of judging if such material was enough to ensure that conclusions of 
the safety assessment were valid. 
Question 33:  Given that Pioneer had notified this product under the regulation concerning the deliberate release of this plant (rather than the novel food regulation), were concerns raised by the lead CA about allergenicity of the truncated  synthetic Cry1F protein relevant to the CA's 
assessment of this product (EC-74/At.17 and 33)? 
Dr. Nutti  
615. Based on the information provided by the applicant (EC-074/At. 01-15) and the specific 
request on allergenicity by the lead CA (EC-074/At.17) and checking EC-074/At.05, page 54, my understanding is that the applicant provided information on the history of safe use of the donor organism and a general explanation on the other ite ms, such as molecular weight of the protein, 
protein degradation in gastric fluids, expression levels  of the protein and glycos ylation of the protein. 
I believe that the applicant was supposed to pres ent experimental data to support this general 
information.  
616. Based on the further information presented by the applicant (EC-074/At.19) I can assume that 
the work carried out by Evans (1998) provides fundamental information on  protein equivalence  WT/DS291/R/Add.6 
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  (maize expressed core CRY1F and microbially-deriv ed trypsinolyzed core CRY1F). However, I could 
not recover such information, presented on tables 10A, 11A, 12A and 13A in EC-074/At. 19) (I could 
not open the files on my computer). So, I cannot asses s if the request from the lead CA was fulfilled.  
617. From EC-074/At.33, I can infer that the se cond package of information provided by the 
applicant seems not to be sufficient as far as experimental data are concerned.  
618. Examining EC-074/At.36, once again no comple te annexes could be found (only pages 
identifying each annex can be visualized, but not the complete papers which were supposed to be 
there).  
619. From all the above exposed, I do not have enoug h information to conclude that the concerns 
raised by the lead CA about allergenicity of the tr uncated synthetic Cry1F protein are relevant to the 
product's assessment. I would like to point out that th is specific process called my attention since it is 
completely different from others I have reviewed, i. e., in my opinion, the requested information is not 
provided in a straight way, and experimental data are not presented in a clear way. 
620. Based on EC-074/At.060, the comments from RIKILT on the work by T. Meyer (1999) 
concerning the need of correct updated data, full description of the methodology, and significant 
homology (according to FAO/WHO Expert Consulta tion on Allergenicity of Foods Derived form 
Biotelchnology, 2001) are, in my opinion, correct. 
Question 34:  Given the information before the Panel, including the original notification and additional information provided by Pioneer (EC-74/At. 18-32, 35-50, and 53-59), was the 
information regarding feed safety, detection me thods and reference materials requested by the 
lead CA (EC-74/At.52 and 60) necessary to ensu re that conclusions of the safety assessment 
were valid? 
Dr. Nutti  
621. Based on EC-074/At.052_SCI, Annex 1B, the requ est from the lead CA [xxx] was necessary.  
622. Based on EC-074/At.052_SCI, Annex 2B, the comments from RIKILT [xxx] are correct.  
623. Based on EC-074/At.052_SCI, Annex 6B, the comments from RIKILT [xxx] are correct. 
624. Although I could not find the quail feeding study within the files, I would like to point out 
that, according to the Codex Guideline for the Condu ct of Food Safety Assessment of Foods Derived 
from Recombinant-DNA Plants (Page 4, paragraph 53) , some foods may require additional testing; 
regarding animal feeding studies, extra studies may be  warranted if changes in the bioavailability of 
nutrients are expected or if the composition is not comparable to conventional foods.  
625. Examining EC074/At.058_SCI, where the detection method is presented, so far as my 
knowledge goes, it seems to be correct (in my opi nion, the notifier has to submit the method, the 
primers sequences and the reference materials, wh ich was done). Although in EC074/At.060 the lead 
CA and RIKILT keep the same requests and comments , I do not feel capable of judging the raised 
issue of intellectual property and confidentiality.  
Question 35:  In your view can EC field trials, in  France, Italy, and Chile, provide compositional 
data on maize kernels that is relevant to evaluating cultivation areas exporting maize to the EC? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-136 
  
  Dr. Nutti  
626. It is not clear to me whether the mentioned EC fi eld trials have already been done or are being 
requested. If they have already been carried out, the Codex Alimentarius Guidelines for the Conduct 
of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003, 
Para 45) states that the location of the trials  sites should be representative of the range of 
environmental conditions under which the plant variet ies 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 s hould be conducted over a sufficient number of generations to allow 
adequate exposure to the variety of conditions met in  nature. Therefore, in this case, I understand that 
the field tests in EC and Chile can be considered as supplementary information to the previous tests 
carried out by the notifiers, although they were not necessary, (specially when  we remember that the 
maize in question if for importation and processing). 
Dr. Andow  
627. Clarification from the Panel: Information provid ed by the notifier makes reference to field 
trials conducted in Chile that (it argues) provide compositional data on maize kernels that would be 
relevant to the evaluation of [?] products exported to  the EC.  See the notifier's response to questions 
from the CA, EC74/At.52_SCI, page 6. 
Relevance to EC maize imports:   
628. The question with the response from the notifier is in EC-74/At.52_SCI, 7 December 2001 
(question originally posed 19 March 2001, EC-74/At.33), as follows. 
Question 12 
The applicant is requested to supply com positional data for kernels harvested from 
geographical areas representative for the co mmercial cultivation of maize 1507 (prior 
to export to the EU).  Data for such areas should include multiple locations within an 
area and cover at least two seasons.  In  addition, these data should include the 
following treatments:  transgenic 1507 ma ize plants treated with glyfosinate, 
untreated transgenic 1507 maize plants, and untreated non-transgenic control plants. 
Pioneer's reply to question 12 
The locations for the field experiments th at are described in the dossier, namely 
France, Italy, and Chile, would be repr esentative for the cultivation areas exporting 
maize to the EU.  GM maize plants cultivat ed at the EU test sites had been either 
treated or not treated with the herbicide glufosinate. 
Comment RIKILT 
RIKILT has not been convinced  by Pioneer's statement that the EU locations would 
be representative of non-EU locations e xporting maize and maize products to the EU. 
629. It is clear that France and Italy cannot be locations representative of areas exporting maize to 
the EU, as they are part of the EU.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  630. World maize export and import statistics are available from the US Department of Agriculture 
Economic Research Service.  These statistics are summarized below. 
World Corn Trade 
Thousand Metric Tons 
Date Created: 12/13/2004  
  2000/01 2001/02 2002/03 2003/04 2004/05 
Exports  December  
Argentina  12,229 8,581 12,349 10,400  10,000 
Brazil  3,741 3,857 3,181 5,818  3,000 
Bulgaria  15 41 191 100  300 
China, Peoples Republic of  7,276 8,611 15,244 7,553  4,000 
EU-25  1,016 2,849 1,995 400  500 
Paraguay  386 262 516 800  600 
Romania  50 135 144 100  1,000 
South Africa, Republic of  1,415 1,182 1,141 797  1,000 
Serbia and Montenegro  50 21 200 50  600 
Thailand  407 184 137 726  450 
Ukraine  397 349 811 1,238  2,000 
Others 1,147 1,201 1,238 1,822  1,165 
Subtotal 28,129 27,273 37,147 29,804  24,615 
United States 48,329 47,271 40,924 48,645  51,000 
World Total 76,458 74,544 78,071 78,449  75,615 
Imports  
Algeria  1,500 1,537 1,643 1,750  1,800 
Belarus  169 126 43 150  150 
Brazil  671 297 521 677  400 
Canada  2,843 4,022 3,846 2,039  2,200 
China, Peoples Republic of  89 39 29 2  200 
Chile  1,362 1,278 933 1,000  1,000 
Colombia  1,857 1,911 2,112 2,100  2,200 
Costa Rica  513 463 514 585  600 
Cuba  119 292 279 475  450 
Dominican Republic  968 1,038 906 824  1,000 
EU-25  3,800 3,801 4,327 5,600  2,500 
Ecuador  149 309 304 475  300 
Egypt  5,268 4,905 4,848 3,800  4,300 
El Salvador  469 287 394 475  450 
Guatemala  549 584 513 500  550 
Honduras  252 217 214 230  200 
Indonesia  1,280 1,149 1,633 1,350  1,300 
Iran  1,265 1,261 2,157 1,700  1,900 
Israel  993 1,021 776 1,400  1,000 
Japan  16,340 16,395 16,863 16,781  16,800 
Jamaica & Dep  221 241 218 225  225 
Jordan  454 439 406 400  450 
Kenya  700 20 82 100  400 
Korea, Democratic Peoples Rep  688 288 144 80  200 
Korea, Republic of  8,743 8,621 8,786 8,783  8,500 
Lebanon  184 263 131 285  250 
Libya  252 235 134 150  200 
Malawi  50 86 25 150  200 
Morocco  966 829 1,054 1,200  1,200 
Mexico  5,928 4,076 5,269 5,707  5,800 
Malaysia  2,588 2,425 2,408 2,100  2,000 WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-138 
  
    2000/01 2001/02 2002/03 2003/04 2004/05 
Mozambique  40 369 413 100  200 
Peru  861 858 917 1,100  1,000 
Panama  249 237 272 300  300 
Zimbabwe  50 311 625 600  600 
Russian Federation  150 534 99 500  600 
Saudi Arabia  1,389 1,268 1,424 1,550  1,600 
South Africa, Republic of  0 726 617 495  200 
Syria  794 892 919 950  1,100 
Tunisia  776 793 734 800  800 
Turkey  608 1,193 1,475 1,050  900 
Taiwan  4,924 4,661 4,681 4,900  4,700 
Venezuela  1,207 515 675 680  800 
Yemen  200 264 252 200  200 
Others 2,872 2,203 2,166 2,022  1,790 
Subtotal 75,350 73,279 76,781 76,340  73,515 
Unaccounted 929 1,063 916 1,768  1,720 
United States 179 202 374 341  380 
World Total 76,458 74,544 78,071 78,449  75,615 
 
Source:  USDA Official Estimates  http://www.fas.usda.gov/psd/complete_tables/GF-table7-88.htm
 
Note: 
 – The international trade year for corn is October/September. 
 – 'Unaccounted' includes grain in transit, reporti ng discrepancies in some countries, and trade to 
countries outside the USDA database. 
 – This table was prepared by the Grain and Feed Division, Commodity and Marketing 
Programs, Foreign Agricultural Service, USDA, Washington DC 20250. Information is 
gathered from official statistics of foreign governments and other foreign source materials, 
reports of U.S. agricultural att aches and Foreign Service officer s, results of office research, 
and related information. 
 
631. It is clear that the US, Argentina, People's Republic of China and Brazil are major exporters 
of maize. 
632.  From a statistical perspective, some reasonable representation of actual imports to the EU 
would seem necessary.  There has been no attempt to do this.  Indeed there seems to be a dismissive 
attitude to the request. 
633. It can be asked if maize from Chile would in fact be representative of maize from other 
regions of the world.  It is likely that for some industrial uses of maize, that there is little need to 
distinguish among regional sources.  Without data supporting this lack of need to distinguish 
geographic sources, it is not possible to assert that Chile would be representative of all importation 
regions. 
634. Hence, maize from  France, Italy, and Chile wo uld not provide compositional data on 
maize kernels that is relevant to evaluating cultivation areas export ing maize to the EC. 
635. Even though the question was not asked by the Panel, the scientific rationale for the request 
for compositional data is not evident from the written  record.  It would seem essential to provide such 
a rationale concomitant with the request for inform ation from the notifier.  More specifically, while I 
could imagine some reasons for such a request, many of these imagined reasons are NOT necessary 
for completing a scientific risk assessment.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  Pioneer/Dow AgroSciences Bt corn Cry1F (1507)  
C/ES/01/01  (EC chronology 75) 
 
Question 36:  Given the information before the Panel, including (EC-75/At.1), was the 
information regarding molecular characterization , toxicity, and environmental impact of this 
product requested by the National Biosafety Committee of Spain (NBC) (EC-75/At.5) necessary 
to ensure that conclusions of the safety assessment were valid? 
(a) Given that Pioneer had notified this product under the regulation concerning the 
deliberate release of this plant (cultivati on), were concerns raised by the lead CA 
on allergenicity and toxicity of the pr oteins expressed by the inserted gene 
sequences relevant to the risk assessment of this product? 
Dr. Nutti  
636. Based on EC-075/At.1, regarding Question 5 on protein expression, the protein used in the 
toxicology and allergenicity tests was obtained in a heterologous system and not in other maize. Thus, 
the notifer provided the correct information, which the lead CA did not understand. The possible reason for the misunderstanding resides in the fact that the same protein is expressed in maize 1507 and in maize 1360. But, it is important to point out that the studies were carried out with protein 
derived from recombinant microorganisms. 
637. Based on EC-075/At.1, regarding Question 6 on protein toxicity and allergenicity, the lead 
CA asks about products which clearly degrade duri ng processing. The answer provided by the notifier 
is very well detailed and comprehensive, clarifyi ng all the topics regarding the safety assessment of 
protein toxicity and allergenicity. My impression is that the lead CA was not the most suitable person to evaluate the case. 
Dr. Andow  
Necessity to ensure validity of safety assessment:  
638. I will cover the toxicity and environmental impa ct parts of this question.  I will address 
whether the information requested by the NBC was necessary to ensure that the conclusions of the 
safety assessment were valid. 
639. The specific information requested by the NBC that is relevant to the part of the question I 
will address is detailed in EC-75/At.05, 28 November 2001, and repeated below. 
Field trials in Spain  
1. In accordance with its rules and pr inciples, the National Biosafety Committee 
considers it necessary to conduct and have the results of experimental trials in Spain before proceeding to examine the applicati on to place the product on the market or 
for the company to give sufficient reasons wh y there is no need to conduct such trials 
in Spain. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-140 
  
  Protein expression  
5. The toxicity and allergenicity tests for CRY1F and PAT proteins must be 
carried out on proteins obtained from 1507 maize, not from 1360 maize which, 
although obtained in the same way, is a different transformation event. 
6. Point 4.3(ii) on page 134 states that irrespective whether or not the process 
degrades the inserted sequences and the CRY1F and PAT proteins, the effects of the product on animal feed are considered in significant since neither the CRY1F and 
PAT genes nor the cry1f and par proteins are toxic or allergenic.  This claim is 
debatable, above all with regard to the possible toxicity of degradation peptides 
compared with full proteins.  Without going any further, Bt protein itself is toxic when processed.  It would therefore be desirable to check that technological 
processing of grain and forage derive d from 1507 maize leads to no specific 
degradation of the proteins analysed.  If it does, it would be necessary to analyse the 
allergenicity or toxicity of the specific degradation products. 
Environmental impact  
9. The information provided by the company on studies is insufficient, 
particularly on the impact on other species and/or the environment.  There are many 
cross-references to unpublished documents.  In order to evaluate the experiments 
conducted, the following documents are needed:  Hoxter et al. 1999 a, b, c and d;  
Higgins, 1999;  Maggi, 1999;  Halliday, 1998b. 
10. Given that the Mediterranean corn borer (Sesamia nonagrioides) is the 
greatest pest in Spain, data are needed on th e efficacy of this transgenic maize against 
this species in the laboratory and in the field (vernier 2001b). 
11. Annex 1, Appendix 1 includes no non-target species of relevance to Spain.  
Species which are endangered, sensitive to ch anges in their habitat and of special 
interest should be covered.  More specifi cally, species occurring at the same time or 
place as maize pollination must be taken into consideration. 
12. The resistance management plan proposes voluntarily reserving 5% of the 
area as a refuge with non-Bt maize, but fails to state that insecticides must not be applied within this area so that it can ser ve as a true refuge.  The monitoring plan 
must be brought into line with the legislation in force. 
640. After receiving responses from the notifier, the NBC amplified their request for experimental 
trials in Spain by requesting additional trials, and evaluations of he rbicide efficacy (EC-75/At.13, 17 
June 2002).  While these requests are not included in the question at hand, they suggest that request 1 
in EC-75/At.05, 28 November 2001, was considered quite important by the NBC. 
Field trials in Spain  
1. After examining the additional information supplied by Pioneer, the National Biosafety Committee repeated that more experi mental trials were needed in Spain and 
that the results should be placed at its dispo sal in order to ascertain the behaviour and 
efficacy of this maize under the different  environmental conditions which can occur  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-141 
 
 
                                                       in Spain and its impact on populations of co rn borer and of other non-target species 
associated with maize crops in Spain. 
2. Data are also needed on evaluations of the efficacy of the herbicide on this 
crop under conditions in Spain, since this c ould depend on the climate in each area or 
region. 
641. The original notification submitted by the notifier on 6 July 2001 was not included in the 
materials.  EC-75/At.01 appears to be the original  Spanish version of EC-75/At.06-11.  This means 
that I cannot assess the necessity of the request in th e context of information already provided in the 
original notification.  Instead, I will have to judge  the necessity of the requested information on the 
presumption that the answers provided by the notifier on 14 February 2002109 to questions 5, 6, 9, 10, 
11 and 12 of EC-75/At.05 were sufficient to m eet the information needs requested.  On this 
presumption, I can determine if the information provi ded was necessary to ensure that conclusions of 
the safety assessment were valid.  As Question 1 apparently was not sufficiently addressed in the 14 February 2002 response, and apparently was still unresolved over a year later (EC-75/At.21, 17 
February 2003), I believe too much time and additio nal information intervened to judge the necessity 
of the original question on the basis of an analysis of the response.  I will evaluate this question 
without reference to the answers provided by the notifier. 
642. Question 5.  Question 5 was necessary to ensure that conclu sions of the safety assessment 
were valid.   It is possible that microbially derived Cry1F protein or Event 1360 derived Cry1F or 
PAT are not the same chemical products.  If they were not the same chemical products, then results 
from toxicity tests could be different, leading to e rroneous conclusions in the safety assessment.  It is 
possible that identical gene sequences in the pl asmid vector could give rise to different gene 
sequences incorporated in the plant.   This has been seen for the cry1 Ab gene that was incorporated 
into Mon810 and Bt11.110 
643. Question 6.  Question 6 was necessary to ensure that conclu sions of the safety assessment 
were valid.   It is possible that stable or transiently quasi-stable degradation products of Cry1F or PAT 
proteins could have effects, either by themselves as degradation products or in reacting with other 
chemicals, such as sugars, even when the parent compound does not react with other chemicals.  I believe stable or quasi-stable degradation products  of Cry proteins in humans have not been found, 
however, such products are known in insects.  Indeed stable degradation products are the basis of the 
toxicity of some Cry proteins to some insects.  Hence this possibility cannot be excluded in other non-
mammalian degradation processes.  The possibility  of degradation products reacting to form 
chemicals with some adverse effect is a hypothetical possibility.  However, the chemical reactions 
that occur in grain processing are complex and fully understood.  It should also be recognized that the 
possibility of such effects may be small. 
644. Question 9.  Question 9 was necessary to ensure that conclu sions of the safety assessment 
were valid.   Actuality a risk assessor can choose to belie ve the interpretation of the data provided by 
the notifier or to examine the data and come to an independent interpretation.  The scientifically sound 
approach would be to examine the data and come to  an independent interpretation.  The question is 
both reasonable and essential. 
645. Question 10.  This question is difficult to unders tand.  Vernier (2001b) is referenced in the 
question.  This report, which was included in the orig inal notification, evaluates lab and field efficacy 
 
109 EC-75/At.01 (English). 
110 Essential Biosafety.  www.es sentialbiosafety.com/main.php. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-142 
  
  of Event 1507 to Sesamia nonagrioides.  The questio n asks for lab and field evaluations of efficacy to 
S. nonagrioides.  Hence, from a literal interpretation of the question, it was not necessary to ensure 
that conclusions of the safety assessment were valid.   Even if we assume that the question was 
requesting field data from Spain, the notifier's answer  clearly states that the field data were collected 
in an area of southern France, and the NCB did not question this in their follow-up questions.  Hence, 
is must be concluded that they decided also that  the question was not essential, as acceptable data had 
already been submitted in the original notifica tion.  The only way that this question could be 
considered essential is if the data provided by th e report by Casteñera (2001), cited in the notifier's 
response filled some significant gap in the Vernier (2001b) study.  As neither of these reports were 
included in the information before the Panel, it cannot be concluded that the Casteñera (2001) report 
filled a crucial gap in the Vernier (2001b) study, and it cannot be concluded that the question was 
essential. 
646. Question 11.  Question 11 was necessary to ensure that conclusions of the safety 
assessment were valid.   The original notification suggested th at most susceptible Lepidoptera would 
not be adversely affected by Event 1507 because exposure levels would be low and the expected 
hazard was also low.  This part of the risk assessment then presume d that all Lepidoptera of potential 
concern would not be adversely affected.  The qu estion was necessary to ensure that the specific 
Lepidoptera (butterflies) of special concern would not be adversely affected.   
647. Question 12.  There is legitimate scientific debates that bear on the necessity of this question.  
One perspective is that a 5% refuge is insufficient for corn borers regardless of  how it is treated and 
that a 20% refuge is essential, but this 20% refuge can be treated with other insecticides.  From this 
perspective, it is the area of refuge that is mo st important as long as the refuge produces some number 
of susceptible moths,111 and Question 12 is not justified because its premises are not valid.  The other 
perspective is that a 5% refuge may be suffici ent if enough corn borers are produced from it.112  In 
other words, refuges should be managed to produce as many susceptible moths as possible.  From this 
perspective, question 12 was necessary to ensure that conclusions of the safety assessment were 
valid.  In either case, discussion of various management options for the refuge is necessary. 
648. Question 1.  The degree that a field trial shoul d be conducted in the actual location of concern 
is of considerable scientific interest and there is not yet a scientific consensus on this issue.  Whether 
data from France and Italy can be used to inform a risk assessment in Spain in a scientifically 
definitive manner is difficult to answer in the abstract.  In general, it has been appreciated for some 
time that climate constrains ecological communiti es and ecosystems creating similarities among them 
even when they are in widely disparate regions of the world.  More recently, climate has been shown 
to similarly structure some biological communities,  especially in comparisons of communities in the 
world's deserts.  Thus, there are reasons to believe that data from France and Italy can be used to 
inform a risk assessment in Spain.  At the same time, it has been widely appreciated that local 
ecological communities and ecosystems often func tions quite differently even from nearby 
superficially similar communities and ecosystems.  For example, for maize en tomology in the US, it 
is unlikely that an extension entomologist in Illinois would accept important results from Iowa, 
Indiana or Ohio as accurate for Illinois without doing some experiments to confirm their applicability.  
                                                      
111 This perspective has been most recently advanced by Ives and Andow, 2002, Evolution of resistance 
to Bt crops: Directional selection in structured environments.  Ecology Letters 5:792-801.  The basic idea is that 
selection is related mostly to the proportion of refuge mo ths that are exposed to selec tion on the Bt crops, which 
is proportional to the relative area of the Bt crops. 
112 This perspective has been widely suggested, but still has not been proved.  The underlying metaphor 
is that the refuge moths dilute out resistance in the Bt crops, and the more refuge moths, the greater the dilution 
effect.  More moths can be produced by producing more moths per unit of refuge or by having larger refuges.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-143 
 
 
  Thus, there are reasons to believe that data from France and Italy may not be used to inform risk 
assessment in Spain, unless some of the critical inform ation is confirmed to be relevant for Spain in 
experiments in Spain.  Based on the exact wording of the question, it cannot be determined which of 
these two perspectives would hold in this case.  In pa rt, the reason for this indeterminacy is that the 
question is so general that it coul d be referring to almost any aspect  of field experimentation.  The 
question should be worded more sp ecifically, both to guide the registrant in answering the question, 
and to be clarify the specific purpose of the question.   As a consequence, while I would conclude that 
questions along the lines of question 1 would be ne cessary to ensure that conclusions of the safety 
assessment were valid, in this case, I must conclude that question 1 was not necessary to ensure that 
conclusions of the safety assessment were valid.  
649. Summary.  With respect to toxicity and environmental impacts, questions 1 and 10 were not 
necessary to ensure that conclusions of the safety assessment were valid, while questions 5, 6, 9, 11 
and 12 were necessary to ensure that conclusi ons of the safety assessment were valid.   
650. Following from this summary, given that th e notifier had notified this product under the 
regulation concerning the deliberate release of this plant (cultivation), the concerns raised by the lead CA on toxicity of the proteins expressed by the in serted gene sequences were relevant to the risk 
assessment of this product. 
651. The notifier submitted the original notification to the Spanish CA (NBC) on 6 July 2001.  The 
NBC requested additional information on 30 Oc tober 2001 and 28 November 2001.  The notifier 
responded to these requests on 14 February 2002.  Th e NBC made additional requests for information 
on 17 June 2002.  From the time of submission to the first request for information 116 days passed.  
From the time of submission of responses to the re quests for information to the 17 June 2002 request 
for additional information, 92 days passed.  This was 208 days total time, and seems longer than necessary to complete the reviews a nd make requests for information. 
Monsanto Roundup Ready corn (NK603)  
C/ES/00/01 (EC chronology 76) 
 
Question 37:  Given the information before the Pa nel, including the notification (EC-76/At.1-2 
and 27), was further information regarding mol ecular characterisation, nutritional analysis, 
and environmental impact requested by the le ad CA (EC-76/At.6) necessary to ensure that 
conclusions of the safety assessment were valid? 
Dr. Nutti  
652. Based on EC-76/At.1-2 and 27, and regarding nutritional analysis, com positional analysis of 
NK603 maize grain has demonstrated substantial equivalence with traditional maize. This is 
supported by lack of differences shown in the results of feeding NK603 to broiler chickens compared 
with birds fed with NK603 parental line or with fi ve commercial reference lines, as well as repeated 
dose feeding studies in rats, which contribute to determine the composition and nutritional 
equivalence. Whatever studies were further requested by the lead CA in EC-76/At.6, such studies 
were not necessary to ensure that conclusions of  the safety assessment were valid since all the 
relevant information had already been provided. In EC-76/At.27, the Spanish Biosafety Commission 
had already estimated that for the uses considered and at the current scientific and technical "state of 
the art", there was no scientific evidences which indi cated any risk for human and animal health of 
NK603 maize. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-144 
  
  Dr. Andow  
Necessity to ensure validity of safety assessment:  
653. I will cover the environmental impact aspects of questions 37 and 38. 
654. The relevant questions from the lead CA are in EC-76/At.5, 15 February 2001 and are 
reproduced below. 
Environmental impact of the GMO  
Although this is not the direct purpose of th is notification, the application covers 
aspects relating to the imminent request for authorization for cultivation in another 
Member State.  In view of this eventua lity, the National Biosafety Committee raises 
the following questions: 
16. Page 14, Section 3 – Survivability:  The comments on plant survival are 
incorrect, given that crop repetition is common in many areas and that, in many cases, grain from fallen ears germinates to produce plants in the next season. 
17. Page 16, Section 7 – Potential interactio ns:  This point must be looked into as 
broadly and deeply as necessary.  The environmental impact of these interactions on target or non-target flora and fauna must be evaluated more thoroughly. 
18. Page 58, Point D.6. – Transferability of genetic material from the genetically 
modified plant to other organisms:  Alt hough the application refers exclusively to 
authorization of the grain, detailed knowledge of the dispersal capacity of the pollen 
under various conditions is n ecessary and would be of relevance for authorization of 
cultivation in the State concerned by the a pplication.  This information could be 
decisive when the time comes to dr aw up a future monitoring plan. 
19. Page 98 – Appendices:  Doses and conditi ons for application of the herbicide 
(phenological condition of the plant, dose and date). 
655. It is clear from the opening paragraph of these questions that the lead CA justifies the 
questions on the basis of an imminent request fo r authorization for cultivation in another Member 
State.  Thus, I conclude that the lead-CA does not believe that the questions on environmental impact 
are necessary to ensure that conclusions  of the safety assessment were valid. 
656. I believe that none of the questions posed under envi ronmental impact are necessary to 
ensure that conclusions of the safety assessment were valid . 
657. Given that the notification is not for cultivati on, whether survival is slightly better in 
continuous maize than in rotated maize ignores the bigger point, which is that maize does not survive 
very well.  While the CA is correct in noting the di fference, this difference is not necessary to ensure 
that conclusions of the safety assessment were valid. 
658. While it is true that potential inte ractions need to be looked into  broadly and deeply if the GM 
crop were to be cultivated, it is not true that such an investigation is  necessary for the present 
notification.  It would be bette r to focus attention on detecting accidental releases and quickly 
eliminating them.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-145 
 
 
  659. Although it is true that detailed information on transferability of genetic material from the 
GM crop to other organisms is needed if the GM crop were to be cultivated, it is not true that detailed 
information is needed for the present notification.   Some information is necessary to consider how 
gene escape can occur either during processing, storag e or transport, but detailed information is not 
necessary. 
660. As the GM plant is not to be cultivated under the present notification, information on 
herbicide application is not needed. 
661. From the time that the notification was received (2  January 2001) to the time that the lead CA 
sent questions for clarification to the notifier (15 Fe bruary 2001), 44 days had elapsed.  This seems to 
be a rapid turn around time.  
Dr. Squire  
662. The weakness of suitable criteria is again at issue here (Notes, paragraphs 2, 7, 8). 
Documentation from the company is least on environmental matters, partly because of changed 
context (what might be an acceptable impact in one part of the world is considered unacceptable in 
another), while the counter-arguments take no st ep towards indicating what standards might be 
applied.  
Question 38:  Given the information before the Panel, including the notification and letter from 
Monsanto providing additional information (EC-76/At.7-9), was additional information necessary regarding molecular composition a nd environmental impacts associated with 
accidental germination requested by the lead CA (EC-76/7-9 and 10) necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Andow  
663. Having received answers from the notifier (5 September 2001), the lead CA requested 
additional information.  On the issue of environm ental impacts, the lead CA asked the following 
question. 
• Although cultivation of this maize is not c overed by this application for marketing 
authorisation, details of the potential environmental impact of any accidental 
dissemination or germination are needed. 
664. Based on the SNIF (EC-76/At.2, 4 August 2000) and the responses to the first set of questions 
from the lead CA (EC-76/At.7-8, 5 September 2001), it is clear that the notifier has not addressed this question.  The notifier believes, probably rightly, that the likelihoo d of accidental dissemination and 
germination (exposure to the environm ent) is small.  If this is true, the notifier is arguing that when 
exposure is small, risk is small.   Consequently, the notifier may believe that it was not necessary to 
address this question. 
665. In either event, the lead CA may reason as follows: if the hazard associated with a rare 
exposure event is large, then the risk may be large.  Hence the question is necessary to ensure that 
conclusions of the safety assessment are valid.   However, it would be helpful to the notifier to 
specify that the lead CA is concerned about large potential environmental impacts.  Moreover, it would be even more helpful to the notifier to  suggest some possibilities.  For example, if 
contamination of conventional produc tion (related to the "coexistence" issue) is a major concern (and WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-146 
  
  is considered an environmental impact), the notif ier would be able to propose how the concern could 
be managed, thereby facilitating the more rapid completion of the notification process. 
666. The time from the responses to the first set of  questions from the lead CA (EC-76/At.7-8, 5 
September 2001) to the time of the second set of questions from the lead CA (EC-76/At.10, 10 
October 2001) was 35 days.  This seems to be a rapid turn around time. 
Dr. Squire  
667. On the more specific question of whether GMHT maize persists (accidental germination), it is 
justified to query the original statement since emergence has been recorded in some southern 
European areas.  
Question 39:  Given the information before the Panel, including the notification and additional 
letter from Monsanto providing additional information (referenced above and EC-76/At.11-12), was additional information regarding molecular characterization and toxicology requested by 
the lead CA (EC-76/At.14) necessary to ensure that conclusions of the safety assessment were 
valid? 
Dr. Nutti  
668. Based on EC-76/At.11-12 and the request by the l ead CA in EC-76/At.14, regarding to animal 
feeding, asking for clarification of the titles of ta bles 2 and 3 on page 24 of Appendix 2 and of their 
content with regard to the calculation of the saf ety margins established and the reasons for the 
differences detected, my opinion is that such a reque st was not necessary to ensure that conclusions of 
the safety assessment were valid.  
Dr. Squire  
669. See answer to question 37 . 
Question 39 bis:  Given the information before the Pa nel, including the notification and 
additional letter from Monsanto providing additional information (previously referenced and EC-76/At.11-12), was additional information regarding allergenicity studies and PCR tests 
requested by Austria (EC-76/At.44) necessary or u seful to ensure that conclusions of the safety 
assessment were valid? 
Dr. Nutti  
670. Answer 39 bis:  Based on EC-76/At.11-12 and the request  by the lead CA in EC-76/At.44, 
regarding to allergenicity studies and PCR tests, my opinion is that such a request was not 
necessary to ensure that conclusions of the safety assessment were valid.  
Monsanto Roundup Ready corn (GA 21 ) 
C/ES/98/01 (EC chronology 78) 
C/GB/97/M3/2 (EC chronology 85)  
Question 40:  Given the information before the Panel, including the application 
(EC-85/At.25-26), questions by Denmark (EC-85/At.32) and responses to these questions 
(EC-85/At.41), was the additional information requested by Denmark (EC-85/At.42) necessary to ensure that conclusions of the safety assessment were valid?  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  Dr. Nutti  
671. Based on the information provided by the applicant (EC-85/At.25-56) and responses to the 
questions raised by Denmark (EC-85/At.41 and EC-85/At.32, respectively), regarding animal feeding 
studies, my understanding is that the applicant has provided sufficient relevant information. 
According to the Codex Alimentarius Guideline fo r the Conduct of Food Safety Assessment of Foods 
Derived from Recombinant-DNA Plants (CAC/GL 45-200 3, paragraph 53), additional animal testing 
will be required if the composition is not comparable  to conventional foods, which is not the case of 
Monsanto's event corn GA 21. 
Question 40bis:   Given the information before the Panel,  including the first whole food study 
and agronomic performance tests (attached, cover letter provided in EC 78/85/At. 19), was a 
second animal whole food study requested by Denmark, Austria and Italy (EC-78/85 /At. 67, 40 
and 72) necessary or useful to identify potential adverse effects that had not been previously identified? 
Dr. Nutti  
672. Answer 40 bis:  Based on 78/85/At. 19 and the request by Denmark, Austria and Italy (EC-
78/85 /At. 67, 40 and 72, asking for a second animal whole feeding study, my opinion is that such a 
request was not necessary to ensure that conclu sions of the safety assessment were valid.  Based 
on the Codex Alimentarius  Guidelines for the Conduct of Food Safety Assessment of Foods Derived 
from Recombinant-DNA Plants (CAC/GL 45-2003), paragraphs 53, my understanding is that 
additional animal feeding studies may be warranted for GM foods if changes in the biovailability of the nutrients are expected or if the composition of  the GM food is not comparable to conventional 
food, and this was not the case of maize GA21. 
Pioneer/Dupont high-oleic soybean (260-05)  
C/NL/98/09 (EC chronology 87) 
Question 41:  Given the information before the Panel, including the notification (EC-87/At.1), additional letters from Monsanto providing additional information (EC-87/At.3, 7, CBI part in 8, and 14) and the conclusion of the Commission on Genetic Modification that this product did not present environmental risks (EC-87/At.8-9), wa s additional informatio n regarding data on 
the composition of high-oleic soybeans and the alteration in the protein profile of this product requested by the lead CA (EC-87/At.11, 13, and 15) necessary to ensure that conclusions of the 
safety assessment were valid? 
Dr. Nutti  
673. Based on the notification (EC-87/At.1), the additional information regarding data on the 
composition of high-oleic soybeans (lectin content and composition data from at least two seasons.) 
and the quantification of the change in the protein profile of this product requested by the lead CA (EC-87/At.11 and 12) were necessary to ensure that conclusions of the safety assessment were valid.  
674. It is important to point out that the lead CA has recognized that the soya oil with the changed 
fatty acid composition is mainly intended for human use, and not for livestock feed. It is therefore not 
expected that these changes will have an impact on livestock feed safety. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-148 
  
  Dr. Squire  
675. Response on environmental risk. This product is  intended for import for processing, not for 
growing as a crop. Its potential for environmental risk – compared to other soybean – is through any 
difference in the waste the processing generates or any difference in the rate of establishment as a 
casual or weedy plant. It would seem that the di fferences in chemical composition of the high-oleic 
soybean are unlikely to generate a different type of waste after processing.  
676. The company indicate the product does not pose a risk through becoming established as a 
plant "since the transgenic soybeans do not differ in their characteristics regarding survival, multiplication and dissemination from commodity soybeans" (paragraph 42 in EC-87 At-1). While 
there are no data presented explicitly on this poi nt, the assertion is  nevertheless well founded. In 
Europe, the soya-bean (soybean) Glycine max (L.), ex ists as an uncommon casual plant, mostly on 
tips and waste ground, originating from imported oil-seed (spilled or dumped), food-refuse and bird-seed. It is very much less common than plants arisi ng from, say, oilseed rape: in the UK, for instance, 
casual soybean was recorded at less than 50 localities over many years in a major compendium of 
alien plants (see reference below). It does not spre ad, is not an agricultural weed and will not cross-
pollinate with local plants. It is possible that im ported high oleic soybean would come to exist as a 
casual plant in Europe, but there is no reason to in dicate that it would exist in greater numbers, for 
longer or at more locations than other soybean. The high-oleic soybean does not have properties that 
would cause it to differ markedly in nutritional or toxic properties, and so affect insects or other wild 
animals, and the evidence and arguments presented about the extremely low risks regarding horizontal 
gene transfer (e.g. to microorganisms) appear correct. Therefore the conclusion of the Commission of 
Genetic Modification that the product did not present environmental risk is sound. The requests for further information (EC-87, At 11, 13, 15) appear to be mainly about safety as a feed, so the additional year's field data (requested) would not provide substantive new information on the plant's 
environmental risk. 
Clement EL, Foster MC (1994) Alien plants of  the British Isles. Botanical Society of the 
British Isles, London. 
Monsanto/Syngenta Roundup Ready sugar beet  
C/BE/99/01 (EC chronology 88)  
Question 42:  Given the information before the Panel, including the notification (EC-88/At.1) 
and additional information provided by the notifier (EC-88/At.10-11), was the information 
regarding allergenicity, molecular characterisa tion, and gene transfer in digestive tracts 
requested by the lead CA (EC-88/At.12) necessary to ensure that conclusions of the safety 
assessment were valid? 
Dr. Nutti  
677. Based on the notification (EC-88 At.1) and additi onal information provided by the notifier 
(EC-88 At.11-12), my understanding is: 
678. EC- 88 At.11_SCI, pg 7, Question 3.1, asks more  information on allergenicity. The additional 
answer is provided at Section 4, pg 13 of  EC-88 At 11, with a very detailed explanation on the allergenicity assessment. The notifiers provided ag ain the references explaining that there are two 
common characteristics snared by most allergens:  fi rst, food allergens are gene rally abundant in food, 
usually greater than 1% of the total protein and, seco nd, food allergens are stable to gastric digestion, 
and a specific test for gastric stability has been est ablished and validated usi ng a broad array of known  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-149 
 
 
  food allergens. Assessment of this two characteris tics along with careful review of the history of 
exposure and search for possible sequence similar ity between the GM protein and known allergens 
can help minimize the risk of transferring a known allergen, one that is possibly going to be cross-
reactive to a known allergen, or one that could have  a high likelihood of being a food allergen. On pg 
13 and 14, the notifiers explained the rationale for the test carried out, the decision three used for the 
allergenic potential proteins encoded by genes tran sferred to genetically modified crops, derived from 
FAO/WHO 1996, ILSI 1996. Although this references and this process were carried out in 1998, it is 
very important to point out that the allergenicity assessment was carried out acco rding to the rules that 
would be established by the Codex Alimentarius  Guidelines for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DN A Plants (CAC/GL 45-2003) and its  Annex on 
Possible Allergenicity Assessment  My understanding in this case is that the necessary information 
was provided by the notifiers in the notification,  and the additional information, although was not 
needed, provided clarification to the lead CA, to  the understanding of the allergenicity assessment. 
679. EC-88 At.11_SCI, pg 7, Question 3.2:  "Can the notifying firms show that the concentration 
of GUS protein in the gastrointestinal tract that appears in people and animals after ingesting food 
products is sufficient protection against any toxici ty caused by the deglucuronidation of endogenous 
or exogenous products?", is properly answered by the notifiers, when they explain that since sugar is 
derived from sugar beet and there is very little if any residual protein, there would be no meaningful 
exposure to GUS protein with the consumption of refi ned sugar.  In my opinion this information was 
already in the notification, th e additional answer was just an explanation to the lead CA. 
680. EC-88 At.11_SCI, pg 7-9, Question 3.3: "On page 64, proteins wich are toxic via acute 
mechanisms needs justification. The same is true of the acute toxicity test". With this question, the 
lead CA asks for justification for the acute gavage study tests done with mice (provided in the notification) and information why this tests has been  carried out with proteins that are toxic.  The 
notifier answered the question, explaining that acute gavage tests are usually performed with proteins 
that are toxic via acute mechanisms, provided th e reference (EPA and Slojab at al, 1992), and 
explained the rationale for using this test with  CP4EPSPS proteins. The notifier also reminded that 
those proteins were rapid degraded in in vitro digestibility studies, providing more information with 
new versions of paragraphs C.2.a (ii), C.2.b (ii), C.2.c (iii) in the Application, in the Appendix of 
Section 4 of the document.  My conclusion, as far as the toxicity of the protein is concerned, is that 
the notifier provided the information requested and l ogical justification why those tests were carried 
out, so the information provided at  EC- 80 At 11 complemented and explained the data submitted in 
the notification ( At 1), clarifying the lead CA, but it is important to point out that the necessary 
information on the toxicity of the protein has been presented at the notification, so further information 
was not necessary to ensure the conclusions of the safety assessment in this topic (toxicity of the 
protein), but it helped very much to understand a ll the issue on toxicity, as the answer was detailed 
and explained not only the tests which were car ried out, but also the specific target tissue, 
measurements of weight and f ood consumption, low toxicity of the GUS protein, and minor 
pathological changes observed at the necropsy, so with the answer provided at AT.11, my 
understanding is that no more information was needed in this topic.  
Question 43:  Given the information before the Panel, including the notification and additional 
information provided by the notifier (EC-88/At.10, 11, 13, 14, 15, 16, and 18-26), was the 
information regarding molecular characterisation and allergenicity of event '77' requested by 
the lead CA (EC-88/At.27-28) necessary to ensure th at conclusions of the safety assessment were 
valid? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-150 
  
  Dr. Nutti  
681. The information required by the lead CA (EC-88 At. 27-28) for allergenicity was not 
necessary to ensure that the conclusions of the saf ety assessment were valid. The previous information 
on this item covered all the points recommended by  WHO/FAO Expert Consultation 1996, and the 
Codex Alimentarius Guidelines for the Conduct of Food Safety Assessment of  Foods Derived from 
Recombinant-DNA Plants (CAC/GL 45-2003) and its Annex on Possible Allergenicity Assessment. 
Monsanto MaisGard Roundup Ready (MON 810 & GA21) corn (stack ) 
C/ES/99/02 (EC chronology 94) 
 
Question 44:  Given the information before the Pane l, including the notification (EC-94/At.1-3), 
was the information requested by the Neth erlands(EC-94/At.12) concerning molecular 
characterization, DNA sequence analysis of the insert ion event, analysis of protein levels, effect 
of glyphosphate treatment, composition, toxico logy and the request for a study on dairy cows 
necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
682. Concerning the information requested by Netherlands in EC-94/At.12, I will answer the 
questions related to my background. 
683. Question 3 – This information is not necessary to ensure the validity of the safety assessment. 
The lead CA was asking for more explanation about the higher level of m EPSPS protein in MON 
810xGA21 maize line, as the Committee did not accept th at they are due to biological variety. My 
opinion is that the explanation given by the notifier was acceptable, since in EC-94/ At 13, the notifier 
presents the results of second year study in order to  test this assumption, and the results confirmed 
that the expression levels were similar.  
684. Question 4 – the Committee asked to be provided data to confirm that glyfosate treatment has 
no effect on the composition of maize plants used  and justification for the statistical analysis 
presented at annex 2 of the dossier. It was also poi nted out that regarding question 3, the glyfosate 
treatment was not considered to be a possible factor  that might influence the level of expression of the 
introduced trait. My understanding is that for the comparison of a GM with a non GM product, 
usually the treatment with herbicide is not required, as the tests are done in orde r to compare the effect 
of the new trait, and not the effect of the herbicide. In this case, the applicants had provided data with glyfosate treated and non-treated product, so the in formation asked was not necessary to ensure the 
safety assessment.  This was confirmed at the answer provided by the applicant at EC-94/ At 13, 
where references were provided that the treatment with glyfosate does not affect the composition of GM maize or GM soybean. 
685. Question 5 – the Committee recognized that data was provided on the comparison of 
MON810x GA21 and the parental lines MON 810 a nd GA 21 for grain and forage, and asked for 
more information, including a comparison of the ne w hybrid with non-transgenic parental lines, as the 
comparison presented was with the transgenic parental lines. The Committee asked for information on the composition of ferulic acid, p-commaric acid, raffinose and inositol, and in this case the Committee accepts the comparison between the new hybr id with the parental transgenic lines. My 
understanding is that there are different approaches that can be used when GM traits have been 
combined by traditional breeding (stacked), one is that the comparison of the new hybrid should be 
done with the GM parental lines, and this GM parental lines should have been compared with 
conventional counterpart; another is that the new hybrid should be compared with non-transgenic  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-151 
 
 
  parental lines. The problem with the second option is  that sometimes the relevant parental lines may 
not been developed or may exist only in a genetic  background which is not comparable to the stacked 
hybrid. 
686. The applicant has chosen the first option for th e comparison, as data was presented with the 
information of the equivalence of GA 21 and MON 810 to their nearest non-transgenic isolines,  and 
also the new hybrid MON810xMONGA21 with the pare ntal transgenic lines. My understanding is 
that the information submitted by the applicant wa s sufficient to ensure the validity of the safety 
assessment.  As far as information on the composition of ferulic acid, p-commaric acid, raffinose and 
inositol, were concerned, my understanding is that this supplementary information was not necessary, 
as the applicant had already submitted information indicating that none of the corresponding pathways 
have been altered by the breeding of  new traits.  The applicant also in formed that Phytic acid has been 
considered an important seconda ry metabolite in maize and its measurement encompasses a 
biologically relevant form of inositol. 
687. Question 6 – toxicological tests, the Committee asked for a semi chronic feeding study on 
mice with grain or meal from MON 810x GA21maize. Based on Codex Alimentarius Guidelines for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003), paragraphs 34 to 43, Assessment of Possibl e Toxicity, we have at para 37 that the use of 
appropriate conventional toxicology  or other studies on the new substance may be necessary, if taking 
into account its function and exposure, there are doubt s on the safety of the new substance.  In this 
case the applicant has provided in the dossier (EC-94/At.1-3), all th e information usually requested 
for the food safety assessment, for toxicological ass essment he presented safety studies on protein 
digestion in mammalian gastric and intestinal sy stems, acute gavage studies in mice, homology to 
known toxins and allergens and exposure to human diet. Based on Codex Alimentarius Guidelines for 
the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants (CAC/GL 
45-2003), paragraphs 53, my unde rstanding is that additional animal feeding studies may be 
warranted for GM foods if changes in the biovail ability of the nutrients are expected or if the 
composition of the GM food is not comparable to c onventional food, that is not the case of the new 
hybrid MON 810x GA21 maize. My understanding is th at the information submitted by the applicant 
was sufficient to ensure the va lidity of the safety assessment. 
Dr. Andow  
Necessity to ensure that conclusions were valid : 
688. I will answer this question with respect to the effect of glyphosphate treatment and 
toxicology. 
689. The relevant question from the Netherlands CA (E C-94/At.12, 17 July 2000) on the effect of 
the glyphosate treatment is reproduced below. 
4. The field trials and block treatment .  In Appendix II of the dossier, the 
compositional analyses of the MON 810 x GA21 maize are described.  The following 
comparisons are made:  components of  MON 810 x GA21 maize/forage with 
components of MON 810 maize/forage (both maize lines not treated with Glyphosate) and components of MON 810 x GA21 maize/forage with components of GA21 maize/forage (both maize lines not treated with glyphosate).  Then, the 
following statement is made:  "the significant differences in component values are 
only relevant where the mean value of the MON 810 x GA21 maize line was either 
greater than or less than both parental lines".  However, this assumption is only viable WT/DS291/R/Add.6 
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  if there is no effect of Glyphosate treatme nt on the composition of the maize lines 
since only half of the maize plants used for analyses (maize lines MON 810 x GA21 
and GA21) are treated with Glyphosate.  Therefore, the Committee would like to be 
provided with data to confirm that Gl yphosate treatment has no effect on the 
composition of the maize plants used and to justify the statistical analyses and comparisons between MON 810 x GA21 maize/forage (not treated with glyphosate) and MON 810 x GA21 maize/forage (treated with glyphosate). 
In relation to question 3:  mEPSPS protein levels in MON 810 x GA21 maize line are 
compared with the levels of mEPSPS protein in the parental maize lines MON 810 
and GA21.  In these comparisons, the Glyphosate treatment was not considered to be a possible factor that might influence the expression levels of the introduced traits. 
690. The relevant question from the Netherlands CA (E C-94/At.12, 17 July 2000) on toxicology is 
reproduced below. 
6. The toxicological tests.  Recently, it was discovered that in genetically 
modified soybeans parts of the vector used  for the modification were scattered over 
the genome of the soybeans.  It can not be excluded that these parts are able to form 
proteins.  The Committee is of the opinion that  other plants that are modified with the 
particle acceleration method also might contain some unknown parts of DNA.  The 
presence and safety of these DNA parts, howev er, can not be guaranteed with the 
current molecular biological techniques.  Therefore, the Committee finds that, beside the molecular biological characterization of the modified genome, a semi-chronic toxicity study with relevant parts or prod ucts of the plants are necessary to assess the 
safety of the modified plant for the consum ers.  In the case of the new maize hybrid 
MON 810 x GA21, this would mean, for example, a semi-chronic feeding study on 
mice with maize grain or meal from the MON 810 x GA21 maize plant. 
691. The statistical analysis used is given in Appendix II, page 90 of EC-94/At.2, 29 February 
2000. 
Statistical analyses of the U.S. and E.U. composition data was conducted separately 
and combined using a mixed model analysis of variance: 
Yijk = U + L i + B ij + T k + e ijk, 
where U = overall mean, L i = random location effect, B ij = random spray block within 
location effect, T k = treatment line effect, and e ijk = residual error.  The component 
values for the RR/YG lines were  compared to those of the corresponding single trait 
parental lines (RR and YG) to determine significant differences.  SAS® software was 
used to generate all summary statistics a nd perform all analyses (SAS Institute, 1989, 
1990, 1996).  Report tables present p-values from SAS® as either <0.001 or the actual 
value truncated to three decimal places. 
692. The experimental design for both the US and EU field studies was similar.  There were six 
sites in the US trial and seven sites in the EU tria l.  At each site the field was split into two glyphosate 
treatments (plus glyphosate or no glyphosate).  All of the RoundUp Ready® (RR) varieties were 
planted in the plus glyphosate whole plot.  Those lacking RR were in the no glyphosate whole plot.  Within each whole plot, the relevant YieldGard
® (YG) varieties (both DeKa lb and Holden parentage)  WT/DS291/R/Add.6 
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  and those lacking YG were planted (presumably randomly) as the split plots within the whole plots.  
Thus there were four split treatments within each of the two whole plots.   
693. From the descrip tion in paragraph 691, it would appear that the not ifier compared RR+ versus 
RR- means based on estimated standard errors of the means from the stated statistical analysis. 
694. In my opinion, the notifier used the wrong statis tical analysis.  The experiment is set up as a 
randomized complete block-split plot desi gn with the following statistical model: 
 
695. where i indicates location, j  the glyphosate treatment and presence/absence of the RR gene, 
and k a treatment level.  Y is the response, µ is the grand mean, RR is the glyphosate treatment/RR 
gene effect, εij is the whole plot error for testing the RR effect, T is the treatment effect, nested within 
split plots, and εik(j) is the residual error.  The T effect can be decomposed into the following 
orthogonal effects: 
T = YG + V + YG * V + YG * RR + V * RR + YG * V * RR 
696. where YG is the effect of the YG gene, V is the effect of parental type (DeKalb versus 
Holden), and the other terms are the interaction effects.  All of the T components have 1 df.  As there 
is no true replication within locations, it is essential to treat locations as replicates or there would be 
no source of error variation.  In doing this, it is readily recognized that locations are identical to 
blocks, so the whole plot design is a randomized  complete block design.   The appropriate ANOVA 
table for this analysis for the EU trial is: 
LEVEL EFFECT df MS F p 
Level 1 Location ( L) 6    
 RR 1    
 Error 1 6    
Level 2 T 6    
  YG 1    
  V 1    
  YG*V 1    
  YG*RR 1    
  V*RR 1    
  YG*V*RR 1    
 Error 2 36    
 
697. This analysis would allow direct statistical test  of all relevant effects.  It should be noted, 
however that the RR gene effect is totally confounded with the effect of the application of glyphosate in the experimental design.  Thus it is not possible to estimate an RR effect independent of a glyphosate effect. 
698. Moreover, the notifier treats each of the many response variables as if they were completely 
independent responses.  Statistically it is inadvi sable to treat each response independently with a 
series of ANOVAs (which is what the notifier did).  In actuality it is likely that many of the response 
variables will be correlated with each other.  Thus, the notifier should have considered several WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-154 
  
  possible multivariate responses, and conducted sever al intelligently planned MANOVAs prior to the 
many ANOVAs.  Statistically it is inadvisable to use all of the data in a single large MANOVA. 
699. Thus the CA was justified to request additi onal information on the glyphosate treatment, the 
statistical analysis, and the comparisons made in Appendix II.  These were necessary to ensure that 
conclusions of the safety assessment were valid. 
700. With respect to the toxicity question, the NL-CA is correct to suggest that there may be parts 
of the vector scattered over the genome.  However,  with respect to maize, it should be possible to 
eliminate most of these via the backcrossing methods used to transfer a transgene into a 
commercializable inbred line.  The only ones that are likely to remain are ones that are closely linked 
to the transgene locus.  It would seem that the notifie r would have other alternatives to the toxicity test 
to address the concern of the Netherlands CA.  By providing details such as the number of backcross generations, it would be possible to calculate a proba bility that vector parts remain scattered around 
the genome.  Soybean, being predominantly selfing would not readily eliminate such vector parts 
from its genome during the plant breeding process.  T hus, while the concern is valid and needs to be 
addressed to ensure that the conclusions of the safety assessment are valid, the request for toxicity testing is not necessary to ensure that the conclusions of the safety assessment were valid for maize. 
701. The notifier submitted the original notification to the NL-CA on 29 February 2000.  The NL-
CA requested additional information on 17 July 2000.  A 139 day interval elapsed.  This seems to be a 
little longer than necessary to complete the review and request additional information. 
Question 44bis:  Given the information before the Panel, including the first whole food study and agronomic performance tests (EC 94/At.3, pp. 40), was a second animal whole food study (EC 94/At.12) necessary or useful to identify po tential adverse effects, including those associated 
with small random DNA insertions, that had not been previously identified? 
Dr. Nutti  
702. Answer 44bis:   Based on (EC 94/At.3, pp. 40), and the request by  the lead CA (EC 
94/At.12),  asking for a second animal whole feedi ng study in order to identify potential adverse 
effects,  my opinion is that such a request was not necessary to ensure that conclusions of the 
safety assessment were valid.   
703. Based on the Codex Alimentarius  Guidelines for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003), paragraphs  53, my understanding 
is that additional animal feeding studies may be warranted for GM foods if changes in the biovailability of the nutrients are expected or if the composition of the GM food is not comparable to conventional food, and this was not the case of maize MON 810 & GA21. 
Question 44ter:   In the context of this corn product which was produced through conventional 
breeding from biotech parents, is data regarding the safety of the biotech parent plants relevant 
to the safety assessment of the hybrid plant pro ducts?  Given the results of the risk assessment 
studies of the biotech parents, were additional studies necessary or useful to ensure that the conclusions of the safety assessment rela ted to the hybrid plants were valid? 
Dr. Nutti  
704. Answer 44ter:    As I already pointed out in my answer of question 44, my understanding is 
that there are different approaches that can be used when GM traits have been combined by traditional  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  breeding (stacked), one is that the comparison of th e new hybrid should be done  with the GM parental 
lines, and this GM parental lines should have been  compared with conventi onal counterpart; another 
is that the new hybrid should be compared with non-transgenic parental lines.  The problem with the 
second option is that sometimes the relevant parent al lines may not been developed or may exist only 
in a genetic background which is not comparable to the stacked hybrid.  The applicant has chosen the 
first option for the comparison, as data was presented with the information of the equivalence of  GA 
21 and MON 810 to their nearest non-transgen ic isolines, and also the new hybrid 
MON810xMONGA21 with  the parental transgenic lines.  My understanding is that the 
information submitted by the applicant was sufficient to ensure the validity of the safety 
assessment.  In this case I believe that given the results of the risk assessment studies of the biotech 
parents, no additional studies were necessary or useful to ensure that the conclusions of the safety 
assessment related to the hybrid plants were valid. 
Novel foods  
Monsanto Roundup Ready corn (GA 21)  
(EC chronology 91) 
 
Question 45:  Given the information before the Pa nel, were there scientific or technical reasons 
which explain why the process of validating the detection method took at least fourteen months 
(June 2002-August 2003)? (See EC-91/At.49-56)? 
Dr. Nutti  
705. Although detection methods are not my main area of expertise, I had analysed the information 
presented at EC-91/At.49-56, and I noticed that at  EC-91/At.50, the applicant submits not only the 
protocol ( methodology) used for the detection, but also comments on the main issues that should be taken into consideration, as the preparation of  standard DNA solution, validation parameters, 
precision of measurements, accuracy, robustness, range and sensitivity. 
706. EC-91/At.51, the applicant informs what are the materials that should be used in the analysis. 
707. EC-91/At.52, the applicant submits more speci fic information on the protocol already sent 
and specific data for the validation of GA21 detection  methodology. 
708. EC-91/At.53, the applicant informs that the reagents will be sent. 
709. EC-91/At.54, the applicant apologizes for the delay and informs that more reagents will be 
sent. Applicant asks information for the amount and type of reagent requested. 
710. EC-91/At.55, JRC extends the deadline and answers the applicant about the amount and type 
of reagents. 
711. EC-91/At.56, JRC sends the draft protocol. 
712. Based on the information available, I have th e impression, that there were no scientific or 
technical reasons which explain why the process of  validating the detection method took at least 
fourteen months. It is important to point out th at the existing method submitted by the applicant at 
EC-91/At.50, was complete and detailed, being alr eady in use, so the JRC was supposed to test and 
validate it. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  Syngenta Bt-11 sweet corn  
(EC chronology 92) 
 
Question 46: Were detection methods commercially  available in 2002 sufficient to enable the 
detection of the transgenic proteins expressed by the plant line Bt11 sweet corn? 
Dr. Nutti  
713. The methods available in 2002 were sufficient to enable to detect the DNA and the protein of 
Bt11sweet corn. 
714. Beginning in the 1990's, commercial protein-b ased and DNA-based detection methods have 
become available.  Both methods can be used in a qualitative and a quantitative way.  Early DNA-
based methods have been mainly designed as qualita tive methods only.  More recently, there has been 
a shift towards quantitative PCR methods. Today, most published methods are based on real-time 
PCR technology that can be operated both in a qualitative and a quantitative way.  Some DNA-based 
methods were designed for the identification of a spec ific event while others were designed to identify 
only a certain vector construct or a common gene tic element (e.g., 35S promoter).  Today, the 
development of these three different types PCR met hods continues.  The selection of method depends 
on the intended purpose.  The experience for protein- based methods is similar to the experience with 
DNA-based methods – there are many commercially available protein-based methods also.  These 
methods can confirm the presence or absence of spec ific proteins expressed by the different biotech 
events. These protein-based methods can be applied in both a quantitative and qualitative fashion. The 
protein based methods, while not event-specific, can identify uniquely most commercial events. 
Dr. Healy  
715. Response :  In 1998, the SCP expressed a favourable opinion about the safety and human 
health impacts of the field maize line Bt-11.  Subsequently the European Commission published its 
decision to grant consent to the marketing of the Bt-11 line of maize, but not the cultivation of this 
line.  In November 1998, Novartis submitted to the Dutch authorities a request for an authorisation of 
food products derived from fresh and processed sweet corn carrying the Bt-11 transformation event.  This request was subsequently sent to the Eur opean Commission and dist ributed to the Member 
States, some of which raised issues of concern.  The Scientific Committee for Food (SCF) reviewed 
the scientific information underpinning the request for authorisation and expressed the view that 'Bt-
11 sweet maize is as safe for human food use as its conventional counterparts'. 
Background : 
716. The Bt-11 corn line contains a single copy of  two transgenes, namely the cry1A(b) and pat 
genes.  The cry1A(b) gene encodes one of the Bt toxins derived from the common bacterium Bacillus 
thuringiensis.  The toxins are selectively active against groups of insects, particularly moths and 
butterflies, beetles, flies and mosquitos.  The Cry1A(b) protein toxin is selectively active against 
lepidopterans (ie moths and butterflies).  The pat gene is derived from a common soil bacterium and 
encodes the enzyme  phosphinothricin acetyl transferase (PAT), which inactivates the herbicide glufosinate ammonium and confers herbicide to lerance to the genetically modified corn. 
717. No other marker genes, including antibiotic resi stance genes were transferred, to Bt-11 corn.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-157 
 
 
  Detection methods : 
718. Methods to detect transgene(s) and their produc t(s) may be based on either the detection of 
specific DNA sequences (Polymersase Chain Reaction; PRC) or on the identification of the proteins 
produced by the transgene(s).  The documents subm itted by Novaris/Syngenta to support the approval 
of products derived from Bt-11 reference several D NA based detection methods for Bt-11 corn lines.  
These include the method of Zimmermann et al (2 000), based on quantitative polymerase PCR at the 
integration site of the transgene, a PCR based me thod subjected to pre-validation studies by the Joint 
Research Centre (EC 92- 59; it is not clear from the available documents if this method is also based 
on the method of Zimmermann et al, 2000) and another method developed by Syngenta in 
conjunction with the Joint Research Centre and s ubjected to validation procedures (EC 92-60, 63, 64, 
65 and 66; Rolling et al 2003).  However, it app ears that none of these DNA based procedures were 
available commercially in 2002 (Codex Inter governmental Taskforce on Foods Derived from 
Biotechnology, 2002; Bonfini et al, 2002). 
719. Methods for the detection of the transgenic pr oteins expressed by Bt-11, as raised in question 
46, could focus on either of the PAT or the Cry1A(b) proteins, as the genes encoding both proteins have been transferred to Bt-11 and both are expres sed in Bt-11 plants.  The availability of detection 
methods for the detection of the PAT protein are discussed under question 17; the discussion here focuses on the detection of the Cyr1A(b) protein. 
720. A method based on the detection of the Cry1A(b)  protein by an antibody was available in 
2002 (Intergovernmental Taskforce on Foods Derive d from Biotechnology, 2002).  This method had 
been developed to quantitatively determine the leve ls of Cry1A(b) in the transgenic corn line 
MON810.  The method was subjected to a large inter-laboratory validation trial to test the performance of a kit based on the method and used co rn flour samples as the test material (Bonfini et 
al, 2002). 
721. While the test method was designed to quantify Cry1A(b) in MON810 plants and their 
derivative food products, the method should be able to  detect Cry1A(b) in any plant variety in which 
this protein is expressed in sufficiently high levels .  It has been demonstrated that the method does 
indeed detect the Cry1A(b) from Bt-11 in samples containing as little as 0.1% Cry1A(b) (Stave, 2002). 
722. It should be noted that the protein based detection method for Bt-11 does not specifically 
detect Bt-11 plants and their food products.  Rather it detects any plant and food product that contains Cry1A(b) protein at detectable levels – a number of crops have been genetically modified with the 
gene encoding Cry1A(b).  This is a general li mitation of protein based detection methods.  
Furthermore, the method is only functional for tho se foods derived from plant tissue that express the 
protein and accurate quantification is not always possible (Stave, 2002).   
723. It is also notable that both DNA and protein based methods are effective in foods only if the 
DNA or protein is retained intact through an y processing (eg DNA and proteins are generally 
removed in oil extraction and refinement processes ) and can be extracted and purified from food 
matrices. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-158 
  
  Conclusion : 
724. The available evidence indicates that an imm unoassay based detection method suitable for the 
detection of Cry1A(b) protein in Bt-11 trange nic plants was commercially available in 2002.113 
                                                      
113 References Dr. Healy:  
 
Australia New Zealand Food Authority (2001).  Guidelines for the Safety Assessment of Foods to be 
included in Standard A18/Standard 1.5.2 – Food Produced Using Gene Technology.  
www.foodstandards.gov.au . 
Bonfidi, L., Simon, K., Heinze, P., Van den Eade, G. (2002).  Report on the GMO Detection and 
Quantification Methods Submitted to Collaborative Studies.  European Commission Joint Research Centre.  
http://biotech.jrc.it/doc/EUR20383Report. 
Codex Alimentarius Commission (2003a).  Principles for the Risk Analysis of Foods Derived from 
Modern Biotechnology.  
Codex Alimentarius Commission (2003b).  Guidelines for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant DNA Plants. 
Codex Alimentarius Commission (2003c).  Annex on  the Assessment of Possible Allergenicity of the 
Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants. 
Codex Alimentarius Commission (2003d).  Guidelines for the Conduct of Food Safety Assessment of 
Foods Produced Using Recombinant DNA Micro-organisms. 
Codex Intergovernmental Taskforce on Foods Derived from Biotechnology (2002).  Report of the 
Second Meeting of the Ad Hoc Working Group on Analytical Methods.  CRD 12. 
European Food Safety Agency (2004) Guidance document of the Scientific Panel on Genetically 
Modified Organisms for the Risk Assessment of Genetically Modified Plants and Derived Food and Feed. The EFSA Journal 99: 1-94. 
Health Canada (1994).  Guidelines for the Safe ty Assessment of Novel Foods.  www.hc-sc.gc.ca. 
Japanese Ministry of Health, Labour and Welfare (2001).  Procedures of Application for Safety 
Assessment of Foods and Food Additives Produced by Recombinant DNA Techniques.  www.mhlw.go.jp/english/topics/food/3-3.html. 
Kuiper, HA., Kleter, GA., Noteborn, Hub PJM., Kok, EJ  (2001).  Assessment of the Food Safety 
Issues Related to Genetically Modified Foods.  The Plant Journal 27: 503-528. 
Organisation for Economic Co-operation and Development (2000).   Report of the Taskforce on Novel 
Food and Feeds.  Organisation for Economic Co-operation and Development, Paris. 
Organisation for Economic Co-operation and Development (2001).  Consensus Document on Key 
Nutrients and Key Toxicants in Low Erucic Acid Rapeseed (Canola).  Series on the Safety of Novel Foods and Feed No.1. Organisation for Economic Co-operation and Development, Paris.  
Organisation for Economic Co-operation and Development (2002).  Consensus Document on 
Compositional Considerations for New Varieties of Potato es: Key Food and Feed Nutrients, Anti nutrients and 
Toxicants.  Series on the Safety of Novel Foods and Feed No.4. Organisation for Economic Co-operation and Development, Paris. 
National Academy of Sciences (2004).  Safety of  Genetically Engineered Foods:  Approaches to 
Identifying Unintended Health Effects.  The National Academies Press.  
Rolling, SB., Vaitilingom, M., Berdal, Kg., Holst-Je nsen, A. (2003).  Event Specific Real-Time 
Quantitative PCR for Genetically Modified Bt-11 Maize.  Eur Food Res Technol. 216: 347-354. 
Scientific Committee on Plants (1999).  Guidance Docu ment to Facilitate Notifiers in the Preparation 
of Plant GMO Dossiers for Consideration by the Scientific Committee on Plants.  (SCP/GMO/103-Final).  
European Commission. 
Stave, JW. (2002).  Protein Immunoassay Methods for Detection of Biotech Crops:  Applications, 
Limitations and Practical Considerations.  J. AOAC Int. 85: 780-786. 
United Kingdom Food Standards Agency (2003).  
www.food.gov.uk/gmdebate/aboutg m/gm_safety?view=GM%20Microsite . 
USA Food and Drug Administration. (1992).  Statement of Policy: Foods Derived From New Plant 
Varieties. Federal Register.  www.cfsan.fda.gov/~lrd/biotechm.html#reg.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-159 
 
 
  Question 47:  Given the information before the Pa nel, were there scientific or technical reasons 
which explain why the process of validating the detection method took twelve months (EC-
92/At.54-56, 57-65, and 66)?  What would constitute an adequate amount of material to be used 
in the detection method validation?  What are adequate performance indicators for pre-
validation results for this product?  
Dr. Nutti  
725. Although detection methods are not my main area of expertise, I had analysed the information 
presented at EC-92/At.54-56, 57-65, and 66 and I no ticed that the applicant submitted the material 
and proposed methodology, JRC tested the method and at EC-92/At.56, JRC points out some 
problems that were found , mainly with the am ount of DNA detected in some samples , asks for 
comments and more material for testing. 
726. EC-92/At.57, JRC explains to the applicant the main issues discussed by phone and 
acknowledge the reception of the material for  re-starting the validation of the tests.  
727. EC-92/At.58, the applicant submits more information on the methodology. 
728. EC-92/At.59, confidential report from JRC, informing that the method submitted by the 
applicant could not be accepted for a full validation before a final method optimization is carried out, 
pointing out problems on the amplification of the GM specific system. JRC informs that they are willing to discuss the problems with th e applicant and share expertise. 
                                                                                                                                                                     
USA Food and Drug Administration (1997).  Consultation Procedures under FDA's 1992 Statement of 
Policy: Foods Derived from New Plant Varieties.  www.cfsan.fda.gov/~lrd/consulpr.html.  
USA Food and Drug Administration (2001).  Proposed Rule: Premarket Notice Concerning 
Bioengineered Foods Premarket Notice Concerning Bioengineered Foods.  
www.cfsan.fda.gov/~lrd/fr010118.html. 
Van Haver E., de Schrijver, A., Devos, Y., Lievens, S., Renckens, S., Moens, W. (2003).  Guidance 
Notes for the Safety Assessment of Gene tically Modified Crops for Food and Feed Use.  Report of the Belgian 
Biosafety Advisory Council.  Scientific Institute of Public Health.   
www.biosafety.be/NF/GuidanceNotes/D ocuments/SafetyAsse ssmentGMFoodFeed. 
Windels, PI., Taverniers, A. Depicker, E. Van Bock staele, and M. De Loose. (2001).  Characterization 
of the Roundup Ready soybean insert. Eur Food Res Technol. 213:107-112. 
World Health Organisation (1987).  Principles fo r the Safety Assessment of Food Additives and 
Contaminants in Food.  Environmental Health Criteria 70.  World Health Organisation, Geneva. 
World Health Organisation (1993).  Health Aspects of Marker Genes in Genetically Modified Plants.  
Report of a WHO Expert Consultation on Foods Derived from Biotechnology.  World Health Organisation, Geneva. 
World Health Organisation (2000).  Safety Aspects of Genetically Modified Foods of Plant Origin.  
Report of the Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology.  World Health Organisation, Geneva. 
World Health Organisation (2001a).  Evaluation of the Allergenicity of Genetically Modified Foods.  
Report of the Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology.  World Health Organisation, Geneva. 
World Health Organisation (2001b).  Safety Assessment of Foods Derived from Genetically Modified 
Micro-organisms.  Report of the Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology.  World Health Organisation, Geneva. 
World Health Organisation (2003).  Safety Assessmen t of Foods Derived from  Genetically Modified 
Animals, including Fish.  Report of the Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology.  World Health Organisation, Geneva. 
Zimmermann, A., Luthy, J, Pauli,U.  (2000).  Event Specific transgene Detection in Bt-11 Corn by 
Quantitative PCR at the Integration Site.  Lebensm.-Wiss.u.-Technol.  33: 210-216. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-160 
  
  729. EC-92/At.61-65, several e-mails are exchanged between the applicant and JRC, about the 
methodology validation. 
730. EC-92/At.66, JRC informs the conclusion of  the validation and acceptance of the method. 
731. Based on the information available, I have th e impression, that there were no scientific or 
technical reasons which explain why the process of validating the detection method took twelve 
months. 
732. I don't have expertise or references to answer about the adequate amount of material to be 
used in the detection method validation and adequate performance indicators for pre-validation results 
for this product. 
Bayer LibertyLink soybeans  
(EC chronology 93) 
 
Question 48:  Given the information before the Panel, what type of data should be used to evaluate substantial equivalence of these soybeans given their intended end-use (human 
consumption)?   Was information regarding  substantial equivalence, presence of PAT
 DNA and 
pat protein requested by the Belgian Biosafety Council (EC-93/At.11) necessary to ensure that 
conclusions of the safety assessment were valid? 
Dr. Nutti  
733. Based on the information provided by the applicant (EC-093/At. 01-2) and the request for 
additional information by the Belgian Biosafet y Council (EC-93/At.11), as far as substantial 
equivalence is concerned, my understanding is that although the notifier provided a good comparative analysis of two transgenic lines and one non-transgen ic line, with information on a large number of 
nutrients and anti-nutrients, the request for data  on composition (soluble and insoluble nutritional 
fibres, vitamin, mineral and trace elements contents) was proper since this information is relevant for 
the comparison. This is due to the fact that, when a product is a source of fibre, as in this case, the 
comparison should take into account its soluble a nd insoluble fibres contents. Besides, products 
derived from soybean are considered to be  a good source of vitamins and minerals. 
734. The request for the company to present information on the presence of PAT DNA and PAT 
protein in derived soya products is also correct , as the notifier presented only data on the protein 
content in the seeds and derived products, but did not present any specific information on PAT protein. 
735. My understanding is that the requests were nece ssary to ensure that the conclusions of the 
safety assessment were valid. 
Question 49:  Given the information before the Pa nel, including the application (EC-93/At.1-2), 
was additional information regarding nutritional and biochemical characterization and toxicity of the transgenic plant requested by the G reek and Italian authorities (EC-93/At.16-17) 
necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
736. Based on the application (EC-93/At.1-2), the request from the Greek authorities (EC-
93/At.16), items a and b, regarding to the information on the analytical methods used for  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-161 
 
 
  determination of anti-nutrients and data on th e nutritional and composition parameters of the 
transgenic and non-transgenic products, is correct, as I could not find this necessary information in the 
dossier.  Based on the application (EC-93/At.1-2), concerning the request from the Italian authorities 
(EC-93/At.17), my understanding is: 
737. Questions 1 and 2, related to the herbicide treat ment in the tests and possible residues of this 
treatment in the final product. My understanding is that the risk assessment conducted here is related 
to the GMO and not to the herbicide, so this info rmation is not relevant fo r the conclusions of the 
safety assessment. It is important to point out that  the herbicide residue in the product has to be  
within the limits established by JEFCA and the Codex Alimentarius, so the herbicide has been 
assessed in a different study. Sometimes, companies that are carrying out the safety assessment of 
herbicide resistant GMOs, perform fi eld tests with and without herbicides, but this is not the main 
objective of the evaluation, as we need to compare the transgenic and non transgenic crops and not the 
utilization of the herbicide. 
738. Question 3, asking detailed information on th e analytical methods used to evaluate 
composition in macro and micro nutrients and the cont ent of anti-nutrironal factors, is correct, as I 
could not find this necessary information in the dossier.  
739. Question 4, about accreditation status of the laboratory that carried out the composition 
analysis, is correct, as according to the Codex Guidelines the analysis should be performed under 
Good Laboratory Practices. 
740. Question 5, asking the study of the acute toxic ity of the PAT protein to be presented, is 
correct, as I could not find this necessary information in the dossier. 
741. Question 7, asking  data on substantial equivalence to be presented on composition or animal 
tests carried out by the company, is correct, as I could not find this necessary information in the 
dossier. 
742. Remark on the necessity of carrying out a study  of sub-acute toxicity to obtain a more 
detailed assessment of toxicological aspects. In my  opinion, if the information on the equivalence 
were properly supplied and an acute toxicity gavage  study was carried out with satisfactory result, it 
would be not necessary to carry out a sub-acute test. As the notification does not present all the 
necessary information on equivalence, I cannot judge this request. 
Question 50:  Given the information before the Panel, including the application and the 
information provided by Aventis Crop Science (EC-93/At.21), was additional information 
regarding nutritional composition requested by Belgium (EC-93/At.23) necessary to ensure that 
conclusions of the safety assessment were valid?  Does any scientific evidence exist to 
demonstrate that genetically-modified soybean varieties are toxic to humans or animals? If so, what risk management options exist to mitigate any such risks? 
Dr. Nutti  
743. Looking at EC-93, At.21 and 22, I understand th at the notifier has provided information with 
four additional data packages on nutritional comp osition of Liberty Link Soybean A2704-12 and 
A5547-127. I could not find these additional information in the files that were sent to me, as At .21. At 22 are only the letters containing the additional information. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-162 
  
  744. In EC-93/At.23, Belgium asks again for the data  on neutral and acid detergent fibre, and as 
stated before, I agree that this is information necessary for the comparison among the transgenic and 
non-transgenic lines. So, I agree with this request  but I cannot find the data packages on nutrition 
composition. Therefore, if the notifiers had pr ovided the requested information on fibre, the 
compositional comparison could be concluded, but it seems that the lead CA could not find these data 
in the additional packages. 
745. As far as the broiler chicken study is concerned, at the original dossier, EC-93/At.2. pg 29, it 
is described that these studies were conducted at the University of Guelph (Leeson 1997 and 1998), 
but I did not find a copy of the study in the dossier or in the supplementary information, so I don´t 
know if the lead CA has the study or not. My understanding is that this specific information is relevant for the risk assessment, and the dossier informs that the results showed no difference, although they are not presented.  The scientific ev idence provided was not sufficient to demonstrate 
that the genetic modified soybean is toxic to humans or animals.  The problem was that the 
information was not complete in order to fulfil  all the steps for the risk assessment. So, before 
concluding that the product was toxic, the request ed information was necessary to conclude the safety 
evaluation. 
746. I would not go into risk management options to mitigate risks, if I am not sure if such risks 
exist. Therefore, my conclusion is that the lead CA could not conclude about the toxicity of the 
product or about the nutritional and co mpositional equivalence either, so it could not be stated that the 
product might be safe or toxic. 
Pioneer/Dow AgroSciences Bt corn Cry1F (1507)  
(EC chronology 95)  
Question 51:  Given the information before the Pa nel, including the application (EC-95/At.1-2) 
and the responses from Pioneer/Dow AgroScienc es (EC-95/At.10-12), was information 
regarding molecular characterization, compositio nal analyses and toxicological analyses of the 
product requested by the Health Council of the Netherlands (EC-95/At.8 and 13) necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
747. Based on the application presented in EC- 95/At.1-2 and the no tifiers' answers in 
EC-95/At.10-12, I will comment on the compositional analysis and the toxicological analysis 
requested by Netherlands  (EC-95/At.8 and 13): 
748. Studies for the analysis of nutrient composition of grain were carried out in Chile (1998 and 
1999), France and Spain (1999), comparing the GMO a nd the conventional crop, and also the use of 
the herbicide, concluding that 1507 maize is compar able and nutritionally equivalent to grain from 
existing commercial maize hybrids and spraying with glufosinate ammonium does not have an effect 
on the nutrient composition of the 1507 maize grain.  The lead CA asked for 3 seasons of field tests in 
order to compare the results, but generally 2 seasons are acceptable. My understanding is that the notifier has provided 2 seasons in Chile and one season in France and Spain. I also understand that the 
locations in Chile, Spain and France are a represen tative set of locations. In EC-95/At.10-12, the 
notifier explains the seasons and informs about other tests carried out in France, Italy and Bulgaria in 
2000, so my understanding is that the notifier has undertaken different  representative places for more 
than 2 seasons so and, therefore, the additional request was not necessary.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-163 
 
 
  749. The lead CA requested that the compositional da ta should be complemented  with levels of Fe, 
Cu, Se, Zn, Vitamin A, vitamin B6 and nicotinic acid.  At In EC-95/At.11, pages 10 to 12 , the notifier 
supplied the requested  data on minerals and Vita min A, vitamin B6 and nicotinic acid. So, my 
understanding is that this additional information covered the necessary items for the nutrient 
comparison, concluding that the GM and non GM crop were equivalent.  My u nderstanding is that the 
additional request was necessary and it was cove red with the supplementary information. 
750. Data on the broiler chicken study was also s upplied in At EC-95/At.11, annex 4 of the 
application. So, the additional request was not necessary. 
751. The Committee asked the original papers of Brooks (2000), Evans (1998), Glatt(1999) 
Herman (2000), Kuhn (1998), Meyer (1999) and Pf ister (1996), which were not included in the 
dossier. The lead CA also pointed out the impor tance of the equivalence of the novel proteins 
expressed in the 1507 maize and the proteins used in the toxicological tests. A 90-day oral toxicity study with maize grain or meal on mice was require d in order to provide additional data that no 
observed negative effects on food safety would result  from a possible unintended change in the 1507 
maize. My understanding is that this additional request was necessary and it was covered with the supplementary information as in EC-95/At.11, the applicant presented all the requested papers, and 
information regarding the equivalence of the proteins (page 13), so this information was properly provided.  As far as the 90-day oral toxicity study with maize grains in rats is concerned, the applicant 
informed that this study was under way and it would be submitted to the Committee by July 2002.   
Furthermore, according to the Codex Alimentarius Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinan t-DNA Plants (CAC/GL 45-2003, paragraph 53), 
additional animal testing will be required if the co mposition is not comparable to conventional foods, 
which is not the case of Pioneer/Dow AgroSciences Bt corn Cry1F (1507). 
Question 52:  Given the information before the Panel, including the application and the 
responses from Pioneer/Dow AgroSciences (referen ced above), was information regarding the 
potential unintended expression of allergenic  proteins requested by Gezondheistsraad 
(EC-95/At.15) necessary to ensure that conclu sions of the safety assessment were valid? 
Dr. Nutti  
752. My understanding of the request in EC-95/At.15 is that the Committee discussed the weight 
of evidence and all information and concluded that sufficient data on the CRY1F protein was 
therefore available, substantiating the food safet y of the 1507 maize regarding the presence of this 
novel protein. So far, as my knowledge goes, the information submitted for allergenicity was enough 
and there was no need for providing additional in formation on putative fusion proteins from the 
flanking regions of the insert in 1507 maize. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-164 
  
  Monsanto Roundup Ready corn (NK603)  
(EC chronology 96)  
Question 53:  Given the information before the Pa nel, including the application (EC-96/At.1-2), 
was information regarding molecular characteriza tion, toxicity effects of unintended changes 
and compositional data requested by Gezondheitsraad (EC-96/At.7) necessary to ensure that 
conclusions of the safety assessment were valid? 
Dr. Nutti  
753. Based on the application presented in EC-96/At.1-2, I will comment on the compositional 
analysis and toxicological analysis requested by Gezondheitsraad (EC-95/At.7): 
754. Question 2, concerning the request for a semi chronic toxicity study in mice or rats, using 
maize grain or meal, in order to rule out possible undesired effects of additiona l, unidentified changes. 
Based on the Codex Alimentarius Guidelines for th e Conduct of Food Safety Assessment of Foods 
Derived from Recombinant-DNA Plants (CAC/GL 45- 2003), paragraphs 34 to 43, Assessment of 
Possible Toxicity, we have at para 37 that the u se of appropriate conventional toxicology or other 
studies on the new substance may be necessary, if ta king into account its function and exposure, there 
are doubts on the safety of the new substance.  In this case the applicant has provided in the dossier 
(EC-96/At.1-2) all the information usually requested  for the food safety assessment, for toxicological 
assessment he presented safety studies on CP4EPS PS protein digestion in mammalian gastric and 
intestinal systems, acute gavage studies in mi ce, homology to known toxins and allergens and 
exposure to human diet.  It was al so confirmed that the GM maize was equivalent in composition and 
nutrition to the conventional counterpa rt. Therefore, in my opinion, there was no need for requesting a 
semi chronic toxicity study in mice or rats, using maize grain or meal, in order to rule out possible 
undesired effects of additional, unidentified cha nges.  Furthermore, according to the Codex 
Alimentarius Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants (CAC/GL 45-2003, paragr aph 53), additional animal testing will be 
required if the composition is not comparable to  conventional foods, which is not the case of 
Monsanto Roundup Ready corn (NK603). 
755. Question 3 asked clarification on the data of the field trials presented in appendix II-IV of the 
application.  My understanding is that the inform ation was there and they were just asking for the 
exact description of the tests and the statistical design. 
Question 53bis:   Given the information before the Panel,  including the first whole food study 
and agronomic performance tests (EC 96/At.2 , pp. 102-103), was a second animal whole food 
study (EC 96/At. 7) necessary or useful to iden tify potential adverse effects, including those 
associated with small random DNA insertions, th at had not been previously identified? 
Dr. Nutti  
756. Answer 53bis:   Based on (EC 96/At.2, pp. 102-103), and the request by  the lead CA (EC 
96/At. 7) asking for a second animal whole feeding stud y in order to identify potential adverse effects, 
my opinion is that such a request was not necessa ry to ensure that conclusions of the safety 
assessment were valid.  
757. Based on the Codex Alimentarius  Guidelines for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003), paragraphs  53, my understanding 
is that additional animal feeding studies may be warranted for GM foods if changes in the  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-165 
 
 
  biovailability of the nutrients are expected or if the composition of the GM food is not comparable to 
conventional food, and this was not the case of maize NK603. 
Question 54:  Given the information before th e Panel, including the application, was 
information requested by Italy (EC-96/At.9) necessary to ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
758. Based on Codex Alimentarius Guidelines for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003), paragraphs  53, my understanding 
is that additional animal feeding studies may be warranted for GM foods if changes in the biovailability of the nutrients are expected or if the composition of the GM food is not comparable to conventional food. So, the request from Italy for more animal feeding studies was not necessary to 
ensure that conclusions of the safety assessment were valid. My understanding is that the dossier 
presented followed not only the OECD consensus document but also the Codex guidelines, as far as 
nutrition, composition and toxicology is concerned. It is clear for me  that the substantial equivalence 
studies compared the GM with the conventional counte rpart. Therefore, my opinion is that the Italian 
request on these topics was not necessary to ensure  that conclusions on the safety assessment were 
valid. I can not answer on the questions related to molecular characterization (a to h). 
Bejo-Zaden Transgenic Radicchio rosso  
(EC chronology 97)  
Question 55:  Given the information before the Panel, including the application (EC-97/At.1), 
and additional information provided by the notifier (EC-97/At.25-28), was additional information requested by the SCF (EC-97/At.20, 22-24, 28, 31, and 30), regarding molecular characterisation, antibiotic resistant marker genes, and substantial equivalence necessary to 
ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
759. Based on the information presented in EC-97/At.1, 25 and 28, I will comment on the 
substantial equivalence item requested by SCF. The notifier has conducted several field tests from 
1994 to 1996, where different characteristics were observed (colour, size of the plants, productivity etc). The notifier presented some data on the com position for substantial equivalence in the first 
dossier. In EC97, At. 28, the SCF informs that th e previous information was formally accepted and 
requested analysis on crude protein and amino acid composition, carotenoids, folic acid and vitamin C. My opinion is that this request is correct, since these parameters are important for the nutritional evaluation of the product. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-166 
  
  Bejo-Zaden Transgenic Green hearted chicory  
(EC chronology 98)  
Question 56:  Given the information before the Panel, including the application (EC-98/At.9) 
and additional information provided by the notifier (EC-98/At.35-37 and 39), was additional 
information requested by the SCF (EC-98/At.30, 32-33, 34, 38, 40 and 41), regarding molecular characterisation, antibiotic resistant marker genes, and substantial equivalence necessary to 
ensure that conclusions of the safety assessment were valid? 
Dr. Nutti  
760. Based on the information presented in EC-98/At.9, 35 and 37, I will comment on the 
substantial equivalence item requested by the SCF.  The notifier has conducted several field tests from 1994 to 1996, where different characteristics were observed (colour, size of the plants, productivity etc).  The notifier presented some data on the composition for the substantial equivalence assessment in the first dossier.  In EC97, At. 33, the SCF stat es that substantial equivalence was claimed on the 
basis of a very small sample under conditions that  have not been clearly described and asks the 
applicant to confirm substantial equivalence over two growing seasons and in six geographical locations.  The SCF also requested care to ensure that appropriate comparators were used and that 
these were compared with an appropriate sample size at each location.  The SCF stated that if substantial equivalence should not be  established, further detailed safe ty examination of the crop must 
be undertaken. I agree with the SCF comments and request in At 33. 
761. In At 35, the applicant informs that the in formation on substantial equivalence was given 
before, as information on chemical composition, taste tests, phenotypical description of breeding lines and varieties, seeds and so on and informs that the data produced on crude protein, amino acid 
composition, biogenic amines, carotenoids, vita mins and bitter compounds provided in may 1999 
should be seen as additional to the information given before.  The applicant pointed out that all this 
information indicates that the GM chicory is equivale nt to the conventional counterpart and there is no 
sense in continuing with experiments for longer periods. 
762. In At 38, the SCF informs that the previ ous information submitted by the notifier on 
November 2000 was formally accepted and requested  analysis on crude protein and amino acid 
composition, carotenoids, folic acid and vitamin C. As I could not find this information on the files submitted by the notifier, my opinion is that this request is correct, as this parameters are important 
for the nutritional evaluation of the product. 
763. My conclusion is that the request from SCF re garding substantial equi valence was necessary 
to ensure that conclusions of the safety assessment were valid.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-167 
 
 
  Pioneer LibertyLink and Bt (T25 x MON 810) corn (stack)  
(EC chronology 101)  
Question 57:  Given the information before the Pa nel, including the application (EC-101/At.1-3) 
and the additional information provided by Pioneer (EC-101/At13), was additional information 
molecular characterization, field trials, seconda ry plant metabolites, and toxicological tests 
requested by the Netherlands (EC-101/At.14) necessa ry to ensure that conclusions of the safety 
assessment were valid? 
Dr. Nutti  
764. Based on the information presented in EC-96/At.1-3, At 13, I will comment on the 
compositional analysis and toxicological analysis requested by The Netherlands (EC-101/At.14): 
765. Question 2 is about field trials and compar ison between the composition of untreated and 
ammonium glufosinate treated samples. In my opinion, the required information is not relevant to ensure that conclusions of the safety assessment were  valid, as in At-13, as I agree with the notifiers' 
explanation that the aim of the safety assessment was not the ammonium glufosinate, but the new 
product, obtained by a crossing T25xMON 810 corn. 
766. Question 3, requests information on the levels of  ferulic acid, p-coumaric acid, raffinose and 
inositol, as the Committee believes that determining the levels of these plant metabolites is important 
to rule out fortuitous changes in the plant meta bolism as result of the genetic modification. My 
opinion is that this information required is not re levant to ensure that conclusions of the safety 
assessment were valid, as the compositional informati on supplied before leads to the conclusion that 
the product was substantial equivalent. I am also of  the opinion that in this case, we have a product 
that is a conventional cross of two GM corns, but this product has not been submitted to a new genetic 
modification, so the possibility of fortuitous changes in the plant seems to be vanishing small, if exists. 
767. Question 4, on toxicological tests, asks for a semi -chronic oral toxicity study on mice or rats 
with maize grain or meal from the hybrid lines, in order to provide additional data of the food safety of this hybrid. I would like to recall the Code x Alimentarius Guidelines for the Conduct of Food 
Safety Assessment of Foods Derived from Recomb inant-DNA Plants (CAC/GL 45-2003), paragraphs 
53, that states that additional animal feeding studi es may be warranted for GM foods if changes in the 
bioavailability of the nutrients are expected or if the composition of the GM food is not comparable to 
conventional food. Therefore, the request from the Ne therlands for semi-chronic oral toxicity study on 
mice or rats with maize grain,  were not necessary to ensure that conclusions of the safety assessment were valid, as the data provided by the notifiers  confirmed that T25 and MON 810 are substantially 
equivalent to other commercial maize. In partic ular, it was shown the absence of expression of any 
other sequence or fragment of the sequence inserted in T25 and MON 810. A far as the new proteins 
expressed in T25 and MON 810 are concerned, for toxicological assessment were presented  studies 
on protein digestion in mammalian gastric and int estinal systems, acute gavage studies in mice, 
homology to known toxins and alle rgens and exposure to human diet, that I understand are sufficient 
for the toxicological assessment.  In  addition, a poultry feeding study has been carried out with grain 
from T25xMON810, T25, MON 810 and non GM control with comparable genetics. The results presented showed that no significant differences were  observed on mortality, body weight grain and 
feed conversion between chickens fed a diet  containing maize grain from T25xMON810, T25, 
MON 810, the non GM control or a standard diet cont aining yellow dent maize. I am of the opinion 
that this additional study confirms that th e conventionally derived T25xMON 810 maize is 
nutritionally equivalent to T25,  MON810 and maize from non-GM co mmercial hybrids, so it would WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-168 
  
  not be necessary to carry out a semi-chronic oral toxi city study with maize or meal, as this study with 
broilers has already provided the information with the grain.  
Dr. Andow  
Necessity to ensure validity : 
768. In this question, I will address field trials, secondary plant metabolites, and toxicological tests. 
769. The questions from the lead CA are reproduced here (EC-101/At.14, 23 April 2001). 
2. The field trials.  The Committee would appreciate receiving the results of the 
comparison between the composition of untreated and glufosinate-ammonium treated 
T25 maize by Aventis, as mentioned in your letter. 
3. Secondary plant metabolites.  In our previous letter we requested information 
on the levels of ferulic acid, p-coumaric acid, raffinose and inositol.  The Committee 
believes that determining the levels of these plant metabolites is important to rule out 
fortuitous changes in the plant metabolism as a result of the genetic modification.  
The Committee has not received this informati on on either the hybrid or both parental 
lines. 
4. Toxicological tests.  Although your remarks about the repeated backcrossing 
to the non-GM inbred line have been noted, the Committee is still convinced that a semi-chronic oral toxicity study on mice or rats with maize grain or meal from the hybrid line is required to provide additional  proof of the food safety of this hybrid. 
770. The necessity of question 2 on composition of treated and untreated T25 maize is difficult to 
determine.  The comparison between untreated T25 maize and untreated maize lacking T25 would seem to provide the necessar y evidence that T25 does or does not affect the composition of maize.  
However, as indicated by the lead CA, it is also pos sible that the application of the herbicide could 
affect the composition of T25 maize.  The notifier makes a compelling point that the herbicide 
registration process should account for all possible a dverse effects of the herbicide.  However, the 
herbicide registration process does not require demons tration of substantial equivalence.  Moreover, 
the herbicide is normally used with the T25 maize.  Thus, there is a scientific justification for 
requiring comparison of T25 with glufosinate, T25 without glufosinate and maize without T25 and 
without glufosinate.  However, I believe that there is a legitimate scientific debate as to whether all 
three are necessary to ensure that conclu sions of the safety assessment were valid. 
771. The necessity of information about secondary plant metabolites can be justified by the 
following argument.  There is a legitimate concern that there are additional transgenes incorporated into the T25 and Mon810 lines that could be ex pressing additional but unknown gene products, and 
that elude detection by present molecular methods.  In addition, it is also possible that the main gene products from T25 or Mon810 could interact with pl ant metabolism, changing the composition of the 
plant.  The likelihood of the possibilities may be small, but it is difficult to argue how small.  Secondary plant compounds include many chemicals that are human health hazards at high enough 
concentrations.  The requested information can be considered to guard against possible changes in 
human health hazard, and therefore can be cons idered necessary to ensure conclusions of the 
safety assessment were valid.   However, it is also possible that requests for information change in a 
way that is not entirely justified.  In this case, this does not appear to be the problem.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-169 
 
 
  772. My response to this question is identical to my response to question 44 in paragraph 700.  
This is not necessary to ensure conclusions of the safety assessment were valid.  
773. The notifier submitted the original notification the the NL-CA on 20 April 2000.  On 17 July 
2000 the NL-CA requested additional information.  On 22 November 2000 the notifier submitted 
responses to this request.  On 23 April 2001 the NL-C A asked for additional information.  From the 
time of original submission to the first request fo r additional information, 88 days passed.  From the 
time of submitting responses to the second request fo r additional information, 152 days elapsed, 
including the winter holidays.  This is a total of 240 days for review.  This seems to be too long, even 
taking into account delays associated with the winter holidays. 
Dr. Squire  
774. Similar difficulties are evident in the exchanges to those in 37-39 and elsewhere! Even so, the 
requests by the Netherlands are arguably consistent with the type of information indicated in the 
Codex Guideline for the conduct of  food safety assessment of fo ods derived from recombinant-DNA 
plants . 
Monsanto/Syngenta Roundup Ready sugar beet (77)  
(EC chronology 102)  
Question 58:  Given the information before the Panel, including the application (EC-102/At.1-20) and the information provide d by Monsanto/Novartis (EC-102/At.22, 26 and 
27-30), was additional information regarding food safety assessment of derived proteins 
requested by the Netherlands (EC-102/At.32) necessa ry to ensure that conclusions of the safety 
assessment were valid?  Did the food safety a ssessments provided by the applicant follow the 
Codex Guideline for the Conduct of Food Safety Assessment of Foods Derived from 
Recombinant-DNA Plants. 
Dr. Nutti  
775. Based on the information submitted by application EC-102/At.1-20 and further information 
provided by Monsanto/Novartis (EC-102/At.22, 26 and 27-30), my understanding is that the 
information requested by the lead CA in EC- 102/At .32, regarding to the derived proteins and the 
request for a semi-chronic oral toxicity test on mice or rats with edible parts of sugar beet, was not 
necessary to ensure that the conc lusions of the safety assessment were valid.  The applicants had 
performed 90-day acute toxicity test with rats. 
776. Based on the Codex Alimentarius Guidelines for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant-DNA Plants (CAC /GL 45-2003), paragraphs  34 to 43, Assessment 
of Possible Toxicity, we have at para 37 that the use of appropriate conventional toxicology or other 
studies on the new substance may be necessary if, taking into account its function and exposure, 
doubts about the safety of the new substance remain. In this case, the appli cant has provided in the 
dossier (EC-102/At.1-20) all the information usua lly requested for the food safety assessment. Also, 
for the toxicological assessment he presented safety studies on protein digestion in mammalian gastric and intestinal systems, acute gavage studies in mice, homology to known toxins and allergens, and 
exposure to human diet. 
777. Based on the Codex Alimentarius Guidelines for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant-DNA Plants (CAC/GL 45-2003), paragraphs  53, my understanding 
is that additional animal feeding studies may be warranted for GM foods if changes in the WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-170 
  
  biovailability of the nutrients are expected or if the composition of the GM food is not comparable to 
conventional food, that is not the case of Monsanto/Syngenta Roundup Ready sugar beet. 
778. It was also confirmed that the GM crop was equivalent in composition and nutrition to the 
conventional counterpart. Therefore, in my opinion,  there was no need for requesting a semi chronic 
toxicity study in mice or rats using the edible pa rts of the sugar beet in order to rule out possible 
undesired effects of additional unidentified changes. 
ISSUE 2  
Background :  In cases where a biotech product has obtained approval for Community-wide 
marketing, individual EC member States may under certain circumstances provisionally prohibit the 
marketing of that product in their own territori es.  Such measures are commonly referred to as 
"safeguard" measures.  
 
It would be useful for the Panel to understand,  
 
(a) For each biotech product for which a safeguar d measure was taken by specified EC member 
States, how the scientific or other docume ntation relied upon by these member States 
compares with: 
 
 (i) the International Standard for Phytosanitary Measures (ISPM) No. 11 for Pest Risk 
Analysis for Quarantine Pests, including its Supplement (EC-130);  
 
 (ii) FAO/WHO Codex Principles for the Ri sk Analysis of Foods Derived from Modern 
Biotechnology (attached); 
 
 (iii) FAO/WHO Codex Guideline for the Conduct of Food Safety Assessment of Foods 
Derived from Recombinant-DNA Plants (attached);  
 
 (iv) FAO/WHO Codex Annex on Possible Allergenicity Assessment (attached); and  
 
 (v) Annex III of the Cartagena Protocol on Biosafety to the Convention on Biological 
Diversity (EC-1). 
 
(b) For each product for which a safeguard me asure was taken by one of the specified EC 
member States, whether the scientific or other documentation relied upon by these member States is sufficient to support the safeguard measures taken. 
 
The SPS Agreement defines risk assessment as:  
 
"The evaluation of the likelihood of entry,  establishment or spread of a pest or disease within the territory of an importi ng Member according to the sanitary or 
phytosanitary measures which might be applied, and of the associated potential 
biological and economic consequences; or the evaluation of the potential for adverse 
effects on human or animal health aris ing from the presence of additives, 
contaminants, toxins or disease-causing or ganisms in food, beverages or feedstuffs." 
(Annex A, paragraph 4)  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-171 
 
 
  Furthermore, the SPS Agreement provides that:  
 
"In the assessment of risks, Members sha ll take into account available scientific 
evidence;  relevant processes and production methods;  relevant inspection, sampling 
and testing methods;  prevalence of specific di seases or pests; existence of pest- or 
disease-free areas; relevant ecologica l and environmental conditions; and 
quarantine or other treatment." (Article 5.2) 
and that:   
 
"In assessing the risk to animal or plant life or health and determining the measure to be applied for achieving the appropriate level  of sanitary or phytosanitary protection 
from such risk, Members sha ll take into account as relevant economic factors:  the 
potential damage in terms of loss of production or sales in the event of the entry, 
establishment or spread of a pest or disease;  the costs of control or eradication in the territory of the importing Member;  and the relative cost-effectiveness of 
alternative approaches to limiting risks." (Article 5.3) 
Questions  
Oilseed rape MS1 x RF1 (notification C/UK/94/M1/1)  
Safeguard measure of France 
Question 59: Given the information before the Pa nel, including the evaluations undertaken by 
the UK (EC-161/At.1), the Scientific Committee on Plants in May 1998 and May 1999 (CDA-35-A and CDA-69, respectively), and the European Commission in its Decision of February 1996 (CDA-62), as well as th e information submitted by France
 with respect to its 
safeguard measure (EC -161/At.3-11; CDA-68, CD A-70, CDA-71), is there any reason to believe 
that the scientific evidence available to France in November 1998 and July 2001 was NOT sufficient to permit it to undertake an appropriate assessment of potential risks to human, plant and animal health, and the environment from th e growing for seed production of oilseed rape 
MS1 x RF1?  If so, what scientific evidence do you believe was insufficient?  
(a) If the evidence was not sufficient in November 1998 and/or in July 2001, was there sufficient evidence available to France in August 2003
 to permit it to 
undertake a more objective assessment of potential risks to human, plant and animal health, and the environment from the growing for seed production of oilseed rape MS1 x RF1?  If not, what scientific evidence do you believe was insufficient?  
Dr. Nutti  
779. EC161 At. 07–BEC considers that the knowledge  which has been acquired makes it possible 
to contemplate cultivating genetically modified, herbicide-tolerant beet, subject to code of practice being applied and biovigilance measures being institu ted.  It requires large scale experiments with 
GM herbicide tolerant oilseed rape, in order to validate methods of managing crops of these varieties.  Finally, BEC recommends that overall consideration be  given to dealing in detail with the question of 
introducing new weed control practices which are b ased on the large scale use of total herbicides.  
EC161–At. 07 – Summary of BEC, states that it is  possible to contemplate cultivating genetically WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-172 
  
  modified, herbicide-tolerant beet, subject to code  of practice being applied and biovigilance measures 
being instituted.  
EC161–At. 08 – Detailed opinion of BEC  
780. Based on the information before the Panel, in cluding the evaluations undertaken by the UK 
(EC-161/At.1), the Scientific Committee on Plan ts in May 1998 and May 1999 (CDA-35-A and 
CDA-69, respectively), and the European Commi ssion in its Decision of February 1996 (CDA-62) 
submitted by application (EC-102/At.1-20) and furt her information provided by Monsanto/Novartis 
(EC-102/At.22, 26 and 27-30), my understanding  is that there was enough scientific evidence 
available to France in November 1998 and July 2001,  information sufficient to permit it to undertake 
an appropriate assessment of potential risks to human , plant and animal health, from the growing for 
seed production of oilseed rape MS1 x RF1.  Environm ental issues are not my field, so I cannot judge 
this point, but all the information for the safety assessment of potential risks to human and animal 
health that was submitted by the applicants and evaluated by UK and SCP were adequate and in 
accordance to the Codex Guidelines (FAO/WHO Codex Principles for the Risk Analysis of Foods 
Derived from Modern Biotechnology; FAO/WHO Code x Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible 
Allergenicity Assessment). 
781. It is important to point out that either the l ead CA (UK) and the SCP concluded that there is 
no evidence to indicate that the placing on the mark et of the oilseed rape MS1 x RF1, with the 
purpose to be used as any other oilseed rape is likely to cause adverse effects on human health and on the environment. 
Dr. Andow  
782. France provided reasons for its safeguard measur e, beginning in 1998 with EC-161/At.2trans.  
Here France indicates that the spread of herbicide resistance and the concomitant loss of efficacy of 
herbicides with small environmental impact are their concerns at the time of implementing the 
safeguard measure.  Specifically France says (in translation) 
• Controlling adventitious flora a nd oilseed rape regrowth in plots in the event of crop 
rotation and in peripheral areas, would be mo re complex.  Consequently, systematic 
recourse to molecules with less favourable ecotoxicological profiles may be a necessity;   
• the use of molecules with a favourable ecot oxicological profile may be lost because 
of their proven loss of effectiveness, whereas these molecules are es pecially used for 
weeding between crops, at field borders and in various environments such as edges of 
railway tracks or roads.   
The possible developments described above would be worsened by: 
• The possibility of an accumulation of non- selective herbicide tolerance genes in 
double-resistant single lines;   
• systematic introduction of these ge nes in all cultivated species.  
783. France also adds that "There is also the ques tion of the impact on agriculture of a possible 
dependency vis-à-vis only two types of genes and active ingredients."    WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-173 
 
 
                                                       784. At the center of this is that France believes th at the probability of escape of the HT transgene 
as oilseed rape volunteers or into wild species is not accurately assessed, and that the efficacy and 
implementation of risk management measures to eliminate HT volunteers and wild species are not 
accurately evaluated.  On the probability of escape, France is concerned because the scientific 
evidence available at the time comes from a few small-scale dispersal experiments.  France believes 
that when GMHT oilseed rape is  commercialized, it will occur at a large spatial scale.  Dispersal 
processes at large spatial scales may exhibit different characteristics than those at small spatial scales.  This is contrary to the Opinion of the SCP,
114 although the SCP does not provide a scientific argument 
against France's concern about spatial scale.  France is also concerned that specifying and implementing the good agricultural practices that would eliminate HT volunteers and wild species will be considerably more difficult than merely allowing present agricultural practices to continue in the expectation that present practices will eliminate these undesired plants.  This directly contradicts 
the SCP's opinion,
115 which seems to imply that normal agricultural practices will be sufficient. 
785. In the study of dispersal in ecology, durin g the 1980s and 1990s it became increasingly 
apparent that measures of dispersal rates and disp ersal kernels (dispersal probability as a function of 
distance) were related to the spatial scale of the measurement.  Estimated dispersal rates are smaller 
when the spatial scale of measurement is smaller.  This is probably a general result of the fact the 
most biological dispersal kernels are highly lept okurtic.  This scale-dependence has also been 
observed for pollen dispersal from oilseed rape.  One study from 1995 suggested this116, and was later 
confirmed in a 1999117 and 2002 publication in Science118 on large-scale pollen dispersal.  Thus, the 
scientific evidence in 1998 on di spersal of oilseed rape pollen w as not sufficient to complete an 
accurate assessment of dispersal probability.  Su fficient data appeared by the end of 2002. 
786. The scientific basis for believing that normal " good" agricultural practices would be sufficient 
to eliminate HT volunteers and weedy relatives was not clearly articulated prior to France's 1998 
decision.  It is likely that the scientific re asoning for believing that normal "good" agricultural 
practices would be sufficient and easy to implem ent was as follows.  Presently (meaning in 1998) 
 
114 CDA-69 SCP Opinion, 18 May 1999 on France's invocation of Article 16 on MS1 x RF1. 
115 CDA-69 SCP Opinion, 18 May 1999 on France's invocation of Article 16 on MS1 x RF1.  The SCP 
states "The available evidence from the scale of release at that time [ 19 May 1998] suggested that volunteers can 
be controlled by agronomic practice (cultivation and the use of an alternative broad spectrum herbicide) 
provided that adequate m onitoring procedures are in place to iden tify spillage, dispersal and any subsequent 
volunteers."  The reference to 19 May 1998 is to CDA-35A  SCP Opinion, 19 May 1998  This Opinion is on MS8 x RF3, not MS1 x RF1.  The SCP considers that resistance can be managed by a cohesive code of practice supported by a strong education prog ram.  Specifically they recommend 
"2. The Committee was also of the opinion that the potential transfer of the herbicide resistance gene to 
wild Brassica relatives is a new issue in Europe in view of the limited scale of release to date.  The Committee has examined the available ev idence from monitoring and research programmes to date.  After evaluating all the 
information available to the Committee, it was concluded that herbicide-tolerant volunteers that may appear 
would be canola plants and not wild Brassica relatives.  Such herbicide-tolerant volunteers could be controlled in subsequent crops by conventional agricultural methods.  The Committee recommends that the introduction of 
herbicide-tolerant crops should be accompanied by: 
i) an agreed code of practice for the particular m odified crop involving the active participation of the 
notifier to promote best practice by farmers. 
ii) a monitoring programme with an agreed design and implementation plan to detect the occurrence 
and the establishment of herbicide-tolerant volunteers and weeds under field conditions in the EU." 
116 Timmons et al. 1995  Euphytica 85: 417-423. 
117 Thompson et al. 1999 in EC-162/At.13. 
118 Pollen-Mediated Movement of Herbicide Resistan ce Between Commercial Canola Fields   Mary A. 
Rieger, Michael Lamond, Christoph er Preston, Stephen B. Powles, and Richard T. Roush   Science  28 June 
2002; 296: 2386-2388. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-174 
  
                                                       oilseed rape volunteers are normally not significant we eds, and in the rare case when they become 
weeds, they can be easily controlled using th e proper herbicide.  Weedy Brassica species are 
important weeds, but these can also be controlle d using appropriate agricultural methods.  Accepting 
that this argument is true for the purposes of this paragraph, what remains uncertain is whether the 
level of weed control that is considered sufficien t for normal agricultural practice is sufficient for 
eliminating HT volunteers and wild speci es to the level desired by France.   
787. Alternatively, the argument might not be true.  There may be years when certain fields of 
GMHT oilseed rape are not harvested at all and the entire crop goes to seed (since this happens 
occasionally for non-transgenic oilseed rape).  Th e subsequent Brassica weed problem may require 
exceptional agricultural practices to bring the fi eld under control.  Such possibilities were not 
considered by the SCP, and France may be concerned about such scenarios.   
788. Finally, France may be convinced (rightly, I think) that agricultural management of HT 
volunteers and wild species will not be as simple as the SCP believes.  Hence the scientific evidence 
in 1998 on the agricultural practices necessary to  eliminate HT volunteers and wild species was not 
sufficient to complete an accurate assessment of risk management practices.  Based on the material in 
EC-161, I could not determine when sufficient inform ation was first available.  In 2001 the French 
Biomolecular Engineering Committee (BEC) called for additional research in this area, but by the 
middle of 2003, the BEC believed that it had sufficient information to complete an assessment.119 
789. France also could have argued in 1998 that ther e was insufficient data to identify all of the 
possible environmental hazards of GMHT oilseed rape.  France could have argued that the molecular characterization was insufficient to identify all transgene products.  It is not clear to me if MS1 x RF1 
hybrids were ever subject to the molecular an alyses performed for the GM crops evaluated under 
Directive 2001/18/EC.  France could have argued that the risk of evolution of resistance in weeds not related to the Brassicaceae had been incompletely  assessed and management of these risks required 
additional scientific data.  These concerns were wi dely appreciated in the early 1990s, but action to 
address them in the EU for GMHT crops did not take place until sometime after 1998.  It is not clear to me that adequate information to address this issu e exists even as of this date in 2005.  France could 
have argued that the data on non-target effects was insufficient.  This claim would have been borne out first by the suggestion in 2000 that GMHT oilseed  rape could adversely affect skylarks in the UK 
followed by the FSE trials in 2003 that suggested some  possible adverse effects.   Sufficient data were 
available to assess these risks by October, 2003.  Finally, recently France appears to argue that 
contamination of conventional o ilseed rape varieties is an important concern (related to the 
"coexistence" issue).  While this risk seems possibl e to assess now, it is not clear that the scientific 
information for justifying the risk management practices is available (this is because I am uncertain about the details of the information available about good agricultural practices noted in 
paragraph 
788. 
 
119 EC-161/At.3trans.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-175 
 
 
  Dr. Snow  
BACKGROUND FOR MY ANSWER 
 
To explain my answer to this question, I include  relevant statements from France, the European 
Commission, and the SCP opinions, along with a few comments below. 
 
1. France  
 
France stated (EC-161/At.3 translation): "These orders banning the placing on the market of 
genetically modified oilseed rape are based on the risk of contamination of crops of conventional 
oilseed rape by transgenic oilseed rape.  In an opinion given in this regard on 16 February 2001, the 
Commission du Génie Biomoléculaire (Biomol ecular Engineering Committ ee) concluded that 
experimentation should be pursued in order to supplement existing scientific knowledge and validate 
methods for managing the cultivation of  genetically modified oilseed rape ." 
 
Also, " A further referral to the Bi omolecular Engineering Committee by the French authorities on 
26 June 2003 aimed to take stock of existing knowle dge on the gene flow in oilseed rape and of the 
identification of risks connected with large-scale cultivation of genetica lly modified herbicide-tolerant 
oilseed rape varieties ." 
 
In addition, in EC-161/At. 4 translation (see excerp ts under Question 60), France listed environmental 
concerns and specific scientific investigations  that were needed to address these concerns. 
 
2. Early European Commission Decision on gluf osinate-tolerant oilseed rape (Feb. 6, 1996)  
 
This favorable decision to place seeds of MS1BnxRF1Bn on the market states that: 
 
"the survival and spread of this herbicide-to lerant swede-rape was evaluated, as well 
as the transfer of the herbicide tolerance gene or the other modified genes to compatible species; whereas it was concluded that the risk of establishment was low 
and that any spread or transfer of the herbic ide tolerance gene could be controlled by 
using existing management strategies." 
As I discuss elsewhere, the assumption that " the risk of establishment is low" is not supported by 
scientific evidence, including evidence th at became available during 1998-2003. 
 
3. Opinions of the Scientific Committee on Plants  
 
These opinions are nearly identical to others deali ng with glufosinate-tolerant oilseed rape.  They 
consider that gene transfer and persistence in wild Brassica rapa is unlikely, that potential problems 
with volunteers can be managed, and that any problem s with the spread of herbicide-resistant weeds 
are agronomic problems rather than environmental on es.  The SCP requested that a code of practice 
and monitoring plans be established to determine wh ether problems emerge with herbicide-tolerant 
volunteers and wild relatives. 
 
Opinion of the Scientific Committee on Plants  regarding the glufosinate to lerant, hybrid rape derived 
from genetically modified parental lines (MS8 x RF3) notified by Plant Genetic Systems (notification C/B/96/01) (Submitted by the Scientif ic Committee on Plants, 19 May 1998
) 
 WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-176 
  
  Excerpts – "The risk assessment assumes that tr ansfer will occur at a low level. The 
relevant question is whether this can be contained by risk management and whether it 
is an environmental or agronomic problem."  
"Available evidence from the scale of release to date suggests that volunteers can be controlled by agronomic prac tice (cultivation and the use of an alternative broad 
spectrum herbicide) provided that adequat e monitoring procedures are in place to 
identify spillage, dispersal and any subsequent volunteers. Normal management methods for wild Brassicae including cultiv ation, rotation and alternative herbicide 
should be maintained." 
"Modified rape is no more invasive than unm odified plants and can be controlled by 
the combination of cultivation and the use of alternative non-selective herbicides. 
Potential transgenic exchange is unlikely to lead to establishment as a result of 
reduced viability of any hybr id plants and competition." 
Opinion of the Scientific Committee on Plants , adopted on 18 May 1999 , on the Invocation by France 
of Article 16 ('safeguard' clause) of Council Directive 90/220/EEC with respect to a genetically modified oilseed rape notification C/UK/94/M1/1 (Plant Genetic Systems N.V.) 
 
Excerpts  – "In its risk assessment the Committee assumed that any such transfer will 
occur at a low level. It therefore considered  the more relevant question, whether this 
can be contained by risk  management and whether it is an environmental or 
agronomic problem." 
"The information provided by the French Competent Authority was taken into consideration by the Committee in formulati ng its original Opinion in 1998 and is not 
considered to change the environmental assessment and advice to the Commission." 
Answer to Question 59 : 
 
790. Given that,  
 (i) the SCP identified concerns about the spread of herbicide resistance to volunteer 
weeds, even though they considered this to be more of an agronomic problem than an 
"environmental" one; 
 
 (ii) the SCP underestimated the extent of gene flow that is to be expected to other oilseed 
rape crops, volunteer weeds, and weedy Brassica rapa; and 
 
 (iii) the SCP recommended that the introduction of herbicide-tolerant crops should be 
accompanied by "ii) a monitoring programme with an agreed design and implementation plan to detect the occurrence and the establishment of herbicide-tolerant volunteers and weeds under field conditions in the EU;" 
 
791. I conclude that France had valid reasons to fo llow the advice of its Biomolecular Engineering 
Committee to carry out more research to "suppl ement existing scientific knowledge and validate 
methods for managing the cultivation of genetically modi fied oilseed rape."  Scientists in France were 
well aware of the fact that transgenes would be dispersed by means of pollen and seeds, making it 
difficult to design management plans that would prevent problems in the future.  These problems 
could be compounded if transgenes for glyphosate tolerance were also approved in oilseed rape and  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-177 
 
 
  other crops, as I explain elsewhere.  One could argue that  future events are not relevant to this isolated 
product, but glyphosate-tolerant oilseed rape has al so been proposed for commercialization in Europe. 
792. SUB-QUESTION TO 59. – If so, what scientific evidence do you believe was insufficient?   
793. My conclusion is that France needed more info rmation about the rate at which the transgene 
for glufosinate tolerance would spread to volunteer plants (including the seed bank) and related 
weeds.  France wanted this information in order to determine whether the types of problems that Canada was experiencing (see above) could be managed in the context of the France's agricultural system and, if so, what the cost would be to farmers. 
794. By 2003, more scientific knowledge was availabl e in the form of peer-reviewed papers and 
reports of farmers' experiences in Canada, but ne w information was still coming to light about the 
spread and persistence of genes for herbicide to lerance (see Context section above, and References). 
Dr. Squire  
795. The view expressed by France was that insufficien t information was available to provide clear 
conclusions on several aspects of cross-pollination and persistence of GMHT oilseed rape. The EC 
Scientific Committee on Plants had considered that  the risks arising from outcrossing to volunteer, 
feral and wild relatives were defi nite, but small because any progeny could be controlled later in the 
rotation. France appeared to take a stronger line, in dicating the risks were larger or more uncertain. 
The EC SPC and the information submitted by France therefore agreed on the nature of this potential problem, but differed on its importance or extent . In November 1998 and July 2001, there was 
knowledge about the mechanisms invol ved in cross-pollination and persistence, but one of France's 
main arguments was based on the up-scaling effect – the uncertainty of what might occur if GMHT 
crops were grown widely in the country (Notes, paragraphs 11, 12) . There was insufficient knowledge 
at that time to be able to predic t accurately, for a country such as France, what the rates of spread and 
cross pollination would be (GM to non-GM) if a large part of the rapeseed areas were GM. 
796. (a) The documentation is also correct when it states that relevant new experimental 
information was being placed before the public (see example references below).  The new information 
was providing greater knowledge of cross-pollination in  oilseed rape, particularly over distances of 
several kilometres. This new information would no t have provided qualitativ ely different knowledge 
(it was already known that oilseed rape could cr oss-pollinate at distance) but would provide better 
quantitative estimates of the pollination frequencies and the subsequent survival of GM hybrids 
among volunteer populations. Even by the end of 2003, there was still uncertainty as to what the field-
to-field cross pollination might be if GMHT crops came to be grown in many fields throughout a landscape in Europe. Data in Europe was confined  to knowledge of crossing from a relatively small 
source (one or a few fields of donor oilseed rape) to a large potential sink (many fields on recipient 
oilseed rape). Work is still in progress, not least as one of the main aims of the SIGMEA project 
(Notes, paragraph 14), to estimate spread and cross-pollination on a regional scale in Europe.
120 
                                                      
120 Rieger MA, Lamond M, Preston C, Powles SB, Roush R. 2002. Pollen-mediated movement of 
herbicide resistance between commercial canola fields. Science 296, 2386-2388. 
Ramsay G, Thompson CE, Squire GR. 2003. Quantifying landscape-scale geneflow in oilseed rape. 
Final report on Project RG 0216, 48 pp. Defra: London. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  Question 60:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by France evaluate the relevant risks to human, plant or animal health, and the 
environment from the growing of oilseed  rape MS1 x RF1 for seed production? 
(a) How does the scientific evidence and oth er documentation submitted by France 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
797. The reasons given by France were mainly relate d to the code of practice being applied and 
biovigilance measures being instituted. These are environmental issues that I cannot answer but, 
again, I would like to point out that there was no scientific evidence regarding to food and feed safety 
assessment, for animal and human consumption, on which France could be based for asking the 
moratorium. 
Dr. Andow  
798. With reference to the SPS Agreem ent, France has evaluated releva nt risks to plant health, and 
expressed some of these risks in terms of their consequent potential effect on human health.  
Specifically, France has taken into account av ailable scientific evidence (Article 5.2). 
799. It is not clear, however, that France conduc ted the risk assessment according to the 
phytosanitary measures which might be applied.  France did not present their safeguard measure as a 
possible phytosanitary measure, and did not conduct the risk assessme nt according to their safeguard 
measure.  Thus it is not clear that France conduc ted the risk assessment consistent with Annex A, 
paragraph 4. 
800. France did take into account relevant economic factors (Article 5.3), however France did not 
explicitly compare the relative cost-effectiveness of alternative approaches to limiting risks. 
801. The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case because 
France argues that there is a plant pest risk. 
802. For those risks within the scope of ISPM 11 the risk assessment process is consistent with 
ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
803. It appears that much of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of France contradict this guidance.  My reading of the 
materials before the Panel is that France did not explicitly address this guidance.  Specifically I note 
Section 3, S1 (measures should be designed in proportion to the risk), Section 3.1 (level of acceptable 
risk should be expressed), Section 3.4 (principle s), and Section 3.4.6 (on prohibition) were not 
explicitly addressed. 
804. The science, documentation and reasoning of Fr ance are consistent with Annex III of the 
Cartagena Protocol on Biosafety to the Convention on Biological Diversity.  Specifically, Annex III, Section 8(f) states "Where there is uncertainty re garding the level of risk, it may be addressed by 
requesting further information on the specific issues of concern or by implem enting appropriate risk 
management strategies and/or monitoring the living modified organism in the receiving environment."  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-179 
 
 
  Dr. Snow  
805. With reference to the SPS definition of a risk  assessment, in EC-161/ At. 4, France stated: 
"The main undesirable effects expected from the ma rketing of genetically modified herbicide tolerant 
oilseed rapes are therefore agronomic and commercial."    
806. To the extent that these concerns are justified in the context of invoking "safeguard" measures 
(which I consider to be a legal question), I conclu de that France had valid reasons for deciding that 
additional scientific research was needed.  My reasons are explained below. 
807. Briefly, France was concerned about the spread  of herbicide-tolerant volunteers and related 
weeds, such as Brassica rapa.  This concern was mentioned repeatedly by the EC Scientific 
Committee on Plants, although the SCP felt that the ri sk could be managed af ter commercialization of 
the product.  The French Biomolecular Engineering Committee felt that this should be studied before 
rather than after de-regulation.  This is understa ndable if one assumes that the spread of herbicide 
tolerance genes is harmful to the environment and to farmers (see above), because after the crop has 
been released it could be very difficult to er adicate unwanted transgenes from volunteer, weedy, or 
cultivated populations.  
808. Based on excerpts from the documentation from France and the USA explanation of risk 
assessments, both of which are included below, the requested research can be viewed as part of a 
standard risk assessment.  The requested research focuses on the "exposure" term reflecting how widely a given harm will occur (as in risk = exposure x harm).   
809. The First Written Submission of the USA, point 103, explains that risk assessments should 
"(2) evaluate the likelihood of entry, establishment or spread of these diseases [or pests], as well as 
the associated potential biological and economic consequences."  Detailed empirical studies about the spread of herbicide-tolerance genes by pollen and inter-specific hybrids are useful for estimating 1) 
how common these genes could become in volunteer and weed populations, 2) whether this problem 
can be mitigated, and 3) what type of monitoring should be considered after commercial release has 
occurred. 
810. In EC-161/At. 4 translation, France stated:  
"Oilseed rape is widely grown in France, covering 1.1 million hectares in 2003, nearly 3 per cent more than in 2002.  It r anks after wheat (4.6 million hectares) and 
maize (1.8 million hectares). ..." 
"The main undesirable effects expected from the marketing of genetically modified herbicide tolerant oilseed rapes are therefore agronomic and commercial.  It would appear that dispersal, at a rate to be spec ified, of the herbicide tolerance genes into 
the environment towards adventitious flora is likely.  Furthermore, dispersal into the environment through introspecific hybridiz ation is inevitable, particularly on the 
borders of fields and along lanes and roads.  Oilseed rape is a highly competitive species and has the capacity to generate regrowth for several yea rs in the following 
rotation crops  ..." 
"Accordingly, in the context of a referral from the Ministry of Agriculture on 6 July 2000, the Biomolecular Engineering Committee issued an opinion on 16 February 2001 (attached), in which it concluded that experimentation should be pursued so as 
to supplement existing scientific knowle dge and validate methods for managing the WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-180 
  
  cultivation of genetically modified oilseed rape .  It found in particular that additional 
knowledge was needed on: 
– The effects that would be produced by sources of pollen larger in size than 
those which had hitherto generated information on the dispersal of oilseed 
rape pollen; 
– pollen dispersal over a long distance, and particularly the role of insect 
transfer; 
– better characterization of particular in terspecific hybrids (amphidiploids), in 
the interests of a better understanding of the species' dynamics; 
– the importance of the impact of islands of persistent oilseed rape on the 
pollination of neighbouring oilseed rape fields, including on those that would 
result from the escape of seeds in the transport phases, and the dynamics of such islands (persistence, extension, ... )." 
"A further referral by the Ministry of Ag riculture to the Biomolecular Engineering 
Committee, on 26 June 2003, aimed to ta ke stock of acquired knowledge regarding 
gene flow in oilseed rape and of the identification of risks relat ed to large scale 
cultivation of genetically modified herbic ide tolerant oilseed rape varieties." 
811. Regarding Question 60 (a), I did not find an I SPM statement about situations that would 
trigger "safeguard measures" while additi onal scientific studies are carried out.   
Dr. Squire  
812. As indicated earlier, the requirements in the international guidelines are quite stringent. It 
could be argued that France's position was compatible  with the tone of the SPS Agreement, Annex A, 
paragraph 4 (including economic as well as biological  consequences) and compatible also with 
ISPM-11 Annex 3 on 'Determining the potential for a LMO to be a pest'. 
Question 61:  Does the scientific evidence and ot her information submitted by France support 
the adoption of a temporary prohibition on the growing of oilseed rape MS1 x RF1 for seed production? In light of any potential risks identified by France, what other risk management options were available in November 1998 and/or July 2001? What other risk management options are now available? 
Dr. Nutti  
813. The reasons given by France were mainly relate d to the code of practice being applied and 
biovigilance measures being instituted. These are envi ronmental issues that I cannot answer, but again 
I would like to point out that there were no scientific evidence regarding to food and feed safety assessment, for animal and human consumption, on which France could be based for asking the moratorium. 
Dr. Andow  
814. The adoption of a temporary prohibition can be ju stified on the basis of the scientific evidence 
and other information submitted by France.    WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-181 
 
 
  815. Several other risk management options could also have been justified in November 1998 and 
July 2001.  Risk management strategies include risk avoidance, risk mitigation, and risk tolerance.  In 
1998 and 2001 mitigation and toleranc e strategies were probably inappr opriate.  Here I consider only 
the risk that France expressed in its  original decision to impose a temporary prohibition.  One risk 
avoidance strategy would have been to allow limited planting in a restricted region.  In the first year, 
this could have been at a scale of a large field trial, and build up from th ere.  This would allow 
determination of scale effects.  Anothe r strategy is outl ined in paragraph 78. 
816. Today several alternative risk management options are available.  In addition to risk 
avoidance as in the previous paragraph, risk mitigat ion strategies may also be possible to control HT 
volunteers and wild species.  It would appear that France is now convinced that if HT volunteers or wild species occur that they can be detected rapidly enough and eliminated. 
Dr. Snow  
817. I do not have enough information to answer this  question.  If the question refers to seed 
production on a very small scale, a temporary pr ohibition presumably would be less urgent and 
possibly unnecessary.  If the plants are grown on a fairly large scale, for example on 1,000 hectares 
per year, the issues at hand are similar to those for the previous questions.   
818. The basic concern is that herbicide resistance genes would spread in conjunction with wider 
use of this herbicide over time, and that other ty pes of herbicide resistance genes might also be 
approved in the future (e.g., glyphosate resistan ce), thereby compounding the problem.  One could 
argue that future events are not relevant to this isolated product, but glyphosate-tolerant oilseed rape has also been proposed for commercialization in Europe. 
Dr. Squire  
819. The risk management options were and are similar to those indicated generally for oilseed 
rape at Responses 6d and 101. The risk of spread and cross-pollination can be reduced by such 
measures but not eliminated. 
Topas 19/2 (notification C/UK/95/M5/1)  
Question 62:  Given that oilseed rape Topas 19/2 was only approved for import of seeds for 
processing, what is the relevance of the findings of the UK farm scale evaluation study (EC-38) 
in terms of the assessment of potential risks from Topas 19/2? 
Dr. Nutti  
820. In the study presented in EC-38, the researchers monitored plants and animals in the field and 
around ploughed edges of the fields called field ma rgins. This was done before, during and after the 
crops were grown and harvested. It was an environmental study, in order to give information for the environmental assessment. In my opinion, this study has no relationship with the safety assessment of Topas 19/2, as the permission for this product was asked for "import of seeds for processing", and not 
for cultivation in Europe. My conclusion is that this study has no releva nce for the assessment of 
potential risks of a product that will be on ly processed and not cultivated in Europe. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-182 
  
  Dr. Andow  
821. The findings of the UK FSE study (EC-38) are not  relevant to the risk assessment for import 
and processing of Topas 19/2.  Their only possible re levance would be in the hazard identification 
step of risk assessment.  However, it is unclear how Topas 19/2 could reach such widespread levels of 
actual (accidental) cultivation to cause such a h azard.  It would require escape during importation 
and/or processing and several years of multiplication at levels similar to the multiplication during oilseed rape seed production and the growing of th ese large quantities on the landscape.  Such large 
quantities would necessitate actual cultivation, presu mably without the knowledge that the seed is 
derived from Topas 19/2.  Even if such a scenario  were possible, there would many, many possible 
ways to manage this risk. 
Dr. Snow  
822. Because the seeds of Topas 19/2 were not inte nded for cultivation, the UK farm scale 
evaluation study bears little or no relevance to this decision.  I assume that any seed spillage that 
might occur when the seeds are delivered could be mana ged, and that it is extremely unlikely that the 
seeds would be cultivated inadvertently.  (It appears that Topas 19/2 was approved for cultivation in the UK in 1996 (EC-162 At. 002-003), but I assume that this earlier decision is not applicable here.)   
823. In EC-162 At. 007, Greece states that "it is certain that the seeds will escape into the 
environment and will give viable plants" in Greece.  Even if this is the case, I do not think the UK 
farm scale evaluations are relevant to the possib ility that feral populations of herbicide-tolerant 
oilseed rape would become established.  The farm scale evaluations would only be relevant if the 
product were cultivated widely. 
Dr. Squire  
824. Topas 19/2 and the Farm scale evaluations (FSE).  
825. The FSE compared the effects of GMHT and conventional weed management. Its results 
should have no bearing on the risk associated w ith the importation of seeds for processing. Even if 
these seeds were spilled and became part of the wa yside feral population or volunteer population in a 
field, they would have no effect unless the management of the field changed away from current management in a way comparable to the differe nces between GMHT and conventional cropping in 
the FSE.   
Safeguard measure of France 
Question 63:  Given the information before the Pa nel, including the evaluations undertaken by 
the UK (EC-162/At.1 to 3), and the SCP in  February 1998 (CDA-63), May 1999 (CDA-65 and 
CDA-73), and the European Commission in its Decision of April 1998 (CDA-61), as well as the information submitted by France
 with respect to its safeguard measure (EC-162/At/5, EC-
161/At.3-11, CDA-64, CDA-66, CDA-67), is there an y reason to believe that the scientific 
evidence available to France in November 1998 and July 2001 was NOT sufficient to permit it to undertake an appropriate assessment of potential risks to human, plant and animal health, and the environment from the import and processing  of oilseed rape Topas 19/2? If so, what 
scientific evidence do you believe was insufficient? 
(a) If the evidence was not sufficient in November 1998 and/or in July 2001, was there sufficient evidence available to France in August 2003
 to permit it to  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-183 
 
 
  undertake a more objective assessment of potential risks to human, plant and 
animal health, and the environment from the import and processing  of oilseed rape Topas 19/2?  If not, what scientific evidence do you believe was insufficient? 
Dr. Nutti  
826. Answer 63: In EC-162/At.003, the lead CA (UK), having assessed the potential risks to 
human health and environment arising from the ge netic modification, proposes to consent to the 
placing on the market of the product for specific uses , such as import of Gm seed for processing of 
food, animal feed and industrial uses of non-li ving processed products arising from the product; 
growing and multiplication of seed for breeding material and for sale; field cropping for grain production for feed, food and industrial uses of  non-living processed products arising from the 
product and had specified the conditions and labelling for this uses.  
827. In CDA-63, it can be observed that in February  1998 the SCP made it clear that the safety 
evaluation was done for importation of seeds only, for placing on the market for food and feed 
purposes.  The SCP concludes that there was no significant risk to human and livestock following 
ingestion of CM seeds.  They considered that the GM product and products th ereof were substantially 
equivalent to the traditional counterpart.  SCP concluded that there was no evidence to indicate that 
the placing on the market of the oilseed rape Topas 19/2, with the purpose to be imported for 
processing and placing on the market for food and f eed uses, is likely to cause adverse effects on 
human health and on the environment. 
828. On CDA-65, it can be observed that on May 1999 the SCP was consulted by the Commission 
on the dossier for Topas 19/2 and the prohibitio n from the French CA, with concerns on the 
environmental impact of genetic escape through  volunteers and hybrids, and the agricultural 
consequence of the spread of herbicide tolerance in both cultivated and non-cropped habitats.  In its 
comments, the SCP emphasizes that the application was for the importation of oilseed rape into 
Europe for processing and not for cultivation and production within member states.  The SCP also explains that the potential for the loss of material  during transport and the possible establishment of 
feral plants in uncultivated habitats was considered in the risk assessments carried out by SCP in forming its opinion of February 1998. They conclude d that the risk of genetic escape from this market 
consent was considered by the SCP to be smal l and the current information submitted by French 
authorities did not change that assessment. 
829. Based on the information presented by the notif iers and by the evaluation of SCP, my 
understanding is that there is NO reason to believe that the scientific evidence available to France in 
November 1998 and July 2001 was NOT sufficient to permit it to undertake an appropriate assessment of potential risks to human, plant and animal health, and the environment from the import and processing of oilseed rape Topas 19/2. 
830. Answer 63a:  In my opinion, the scientific evidence presented was sufficient in 1998 and 
2003.   
Dr. Andow  
831. This is a notification for importation a nd processing, not for cultivation (despite 
EC-162/At.1-3 stating that the UK evaluates it for cultivation). 
832. France relies on the same rationale here as us ed for MS1 x RF1 (Questions 59-61), which I 
have reviewed previously in paragraphs 782-783 and will not repeat here.  The key difference is that WT/DS291/R/Add.6 
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Page H-184 
  
  MS1 x RF1 was for cultivation and seed production as well as importation and processing.  There are 
also minor, formal differences in the Opinion of  the SCP that have no consequence for this 
discussion.121 
833. The argument used by France th at was based on spatial scale does not hold for this case.  
With importation and processing, it is highly unlikely that large-scale production of GMHT oilseed rape is possible.  Thus, the data on small-scale di spersal is probably sufficient to complete a risk 
assessment even in 1998. 
834. Moreover, the hazard of widespread HT resistan ce in oilseed rape or related wild species does 
not hold for this case.  This hazard is also scale-dependent, and with the small-scale releases and poor survival expected in spillage and other accidental rel eases, it is not feasible that this hazard will occur.  
Even if it were possible (see paragraph 
821), there would many, many other possible ways to manage 
this risk short of a prohibition.  Thus, the rationale stated by France does not argue that a risk exists that requires management. 
835. France also could have argued in 1998 that ther e was insufficient data to identify all of the 
possible environmental hazards of GMHT oilseed rape.  (1) France could have argued that the molecular characterization was insufficient to identify all transgene products.  France could have concluded that there may be risks stemming from these  unidentified transgene products (if they exist) 
that would require a safeguard measure.  It is not clear to me if Topas 19/2 was ever subject to the 
molecular analyses performed for the GM crops evaluated under Directive 2001/18/EC.  (2) Recently 
France appears to argue that contamination of conventional oilseed rape varieties is an important hazard (related to the "coexistence" issue).  This is a hazard that could occur from the small-scale releases expected by accidental spilla ge.  The risk associated with this hazard is probably possible to 
assess now, but I do not have access to the scientific information on the risk management practices available to me to make a more certain statement. 
836. Such possible hazards would have allowed France to argue that there is a risk, and that the 
risk management measures proposed by the SC P were not supported sufficiently by science.122  The 
scientific evidence in 1998 on the agricultural practices necessary to eliminate HT volunteers and wild species resulting from spillage may not have been su fficient to complete an accurate assessment of 
risk management practices.  Based on the materi al in EC-161 and EC-162,  I could not determine 
when sufficient information was first available.  Th e information needed would be substantially less 
than for MS1 x RF1.   
837. Given the information before the Panel, Fran ce could have argued in November 1998 that 
there was insufficient evidence to complete a risk assessment.  However, I believe that had France 
collected the necessary data to complete this ri sk assessment promptly after implementing their 
temporary prohibition that they could have had sufficient data to make a decision in 2001. 
Dr. Snow  
838. In summary, I did not find any convincing ar guments for why further scientific research 
would be needed to investigate environmental effects of a product that is only intended for import and processing and not for cultivation. 
                                                      
121 CDA-63, CDA-65, CDA-73. 
122 This is discussed in more detail in my response to question 59, paragraph 786.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  839. See ANSWER 62 for explanation.  Because the seeds of Topas 19/2 were not intended for 
cultivation, the need for environmental assessments a ppears to be very low to non-existent.  I assume 
that any seed spillage that might o ccur when the seeds are delivered could be managed and that it is 
extremely unlikely that the seeds would be cultivated inadvertently.  The only conceivable risk that I 
can imagine is that feral volunteer populations woul d cross-pollinate with weedy Brassica rapa, giving 
this weed the trait of resistance to glufosinate,  and the weeds would become more abundant because 
farmers would repeatedly spray these populations with glufosinate (killing off other weeds and favoring the proliferation of the herbicide-resistan t weeds).  This scenario seems extremely unlikely 
for the case of GM seeds that are imported for processing and not cultivation.  
840. I do not understand why France states " These orders banning the placing on the market of 
genetically modified oilseed rape are based on the risk of contamination of crops of conventional 
oilseed rape by transgenic oilseed rape " with regard to Topas 19/2  (EC-161 At. 003 translation). 
841. ANSWER 63 (a):  My conclusion is that I did not find any convincing arguments for why 
further scientific research would be needed to inv estigate environmental effects of a product that is 
only intended for import and processing and not for cultivation.  See ANSWERS 62 and 63. 
Question 64:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by France evaluate the relevant risks to human, plant or animal health, and the 
environment from the import and pro cessing of oilseed rape Topas 19/2? 
(a) How does the scientific evidence and oth er documentation submitted by France 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above?  
Dr. Nutti  
842. Environmental issues are not my field, so I can not judge this point, but all the information for 
the safety assessment of potential risks to human and animal health that was submitted by the 
applicants and evaluated by UK and SCP were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants; FAO/WHO Codex Anne x on Possible Allergenicity Assessment). 
Dr. Andow  
843. With reference to the SPS Agreement, France did no t identify a relevant risk to plant health.  
However, it would have been possible to identif y a relevant risk to plant health (paragraph 789).  
Specifically, France did not fully take into account av ailable scientific evidence (Article 5.2).  As a 
consequence, the argument was undercut by a faulty analysis and France missed opportunities to make a stronger scientific argument. 
844. Under the assumption that France had identified a relevant risk to plant health, it is not clear 
that France conducted the risk assessment according to the phytosanitary measures which might be applied.  France did not present the safeguard me asure as a possible phytosanitary measure.  France 
did not conduct the risk assessment according to this proposed safeguard measure.   Thus it is not clear 
that France conducted the risk assessment consistent with Annex A, paragraph 4. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-186 
  
  845. France did take into account relevant economic factors (Article 5.3), however France did not 
explicitly compare the relative cost-effectiveness of alternative approaches to limiting risks. 
846. The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6, and that argument holds for this case.  While 
France did not identify a potential pest risk, it w as possible to identify a potential pest risk under 
which ISPM 11 could be considered.  Thus, ISPM 11 could be invoked. 
847. For those risks within the scope of ISPM 11 the risk assessment process would be consistent 
with ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
848. It appears that much of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of France contradict this guidance.  My reading of the 
materials before the Panel is that France did not explicitly address this guidance.  Specifically I note 
Section 3, S1 (measures should be designed in proportion to the risk), Section 3.1 (level of acceptable risk should be expressed), Section 3.4 (principle s), and Section 3.4.6 (on prohibition) were not 
explicitly addressed. 
849. The science, documentation and reasoning of Fr ance are consistent with Annex III of the 
Cartagena Protocol on Biosafety to the Convention on Biological Diversity.  Specifically, Annex III, Section 8(f) states "Where there is uncertainty re garding the level of risk, it may be addressed by 
requesting further information on the specific issues of concern or by implem enting appropriate risk 
management strategies and/or monitoring the living modified organism in the receiving environment." 
Dr. Snow  
850. ANSWERS 64 and 64 (a):  My conclusion is that I did not find any convincing arguments for 
why further scientific research woul d be needed to investigate environmental effects of a product that 
is only intended for import and processing and not fo r cultivation, so the question about international 
guidelines seems irrelevant.  See ANSWER 63.   
Question 65:  Does the scientific evidence and ot her information submitted by France support 
the adoption of a temporary prohibition on th e import and processing of oilseed rape Topas 
19/2?  In light of any potential risks identified by France, what other risk management options were available in November 1998 and/or July 2001? What other risk management options are now available? 
Dr. Nutti  
851. As far as my knowledge goes, the scientific ev idence submitted by France does  not support a 
temporary prohibition on the import and processing of oilseed rape Topas 19/2. 
Dr. Andow  
852. The scientific evidence and other information submitted by France does not support the 
adoption of a temporary prohibition on the import and processing of oilseed rape Topas 19/2.  
However, scientific evidence and other information before the Panel could be used to support the 
adoption of a temporary prohibition on the import and processing of oilseed rape Topas 19/2.  Even on these grounds, a temporary pr ohibition probably could not be justified past 2001.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-187 
 
 
  853. Several other risk management options could have been justified in November 1998.  Risk 
management strategies include risk avoidance, risk mitigation, and risk tolerance.  In 1998 mitigation 
and tolerance strategies were proba bly inappropriate.  Another risk avoidance strategy would have 
been to request additional molecular characteriz ation data and allow limited importation with 
attendant monitoring so that the practical aspects of controlling escapes from spillage could experienced. 
854. These options were available in 2001 and remain t oday.  In addition risk mitigation strategies 
may also be possible to control HT volunteers and wild species. 
Dr. Snow  
855. In summary, I did not find any convincing ar guments for why further scientific research 
would be needed to investigate environmental effects of a product that is only intended for import and processing and not for cultivation, so the question a bout risk management options seems irrelevant.  
See ANSWER 63. 
Safeguard measure of Greece 
Question 66:  Given the information before the Pa nel, including the evaluations undertaken by 
the UK (EC-162/At.1 to 3), and the SCP in  February 1998 (CDA-63), May 1999 (CDA-65 and 
CDA-73), and the European Commission in its Decision of April 1998 (CDA-61), as well as the information submitted by Greece 
with respect to its safeguard measure (EC-162/At. 4, CDA-72), 
is there any reason to believe that the scientifi c evidence available to Greece in September 1998 
was NOT sufficient to permit it to undertake an appropriate assessment of potential risks to human, plant and animal health, and the envi ronment from the import and processing of 
oilseed rape Topas 19/2? If so, what scienti fic evidence do you believe was insufficient? 
(a) If the evidence was not sufficient in  September 1998, was there sufficient 
evidence available to Greece in August 2003  to permit it to undertake a more 
objective assessment of potential risks to human, plant and animal health, and 
the environment from the import and pro cessing of oilseed rape Topas 19/2 (EC-
162/At.6  to 13)?  If not, what scientific evidence do you believe was insufficient? 
Dr. Nutti  
856. Answer 66:  On CDA-73, the SCP answers the points risen by the Greek CA, and does not 
change their previous risk assessment.  The SCP ex plains that the potential for the loss of material 
during transport and the possible establishment of fera l plants in uncultivated habitats was considered 
in the risk assessments carried out by SCP in forming its opinion of February 1998.  The SCP points out that in the absence of the use of glufosinate ammonium to apply selective pressure, modified rape 
is not more invasive than unmodified rape and o ilseed rape is not grown commercially in Greece.  
They concluded that the risk of genetic escape from th is market consent was considered by the SCP to 
be small and the current information submitted by Greek authorities does not change that assessment. 
857. Based on the information presented by notifiers and by the evaluation of SCP, my 
understanding is there is NO reason to believe th at the scientific evidence available to Greece on 
September 1998 was NOT sufficient to permit it to undertake an appropriate assessment of potential 
risks to human, plant and anim al health, and the environment from the import and processing of 
oilseed rape Topas 19/2. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-188 
  
  858. Answer 66a:  In my opinion, the scientific evidence presented was sufficient in 1998 and 
2003.  
Dr. Andow  
859. This should be considered a continuation of  my responses to Questions 62-65.  In EC-
162/At.7 Greece identifies three risks to human, plant or animal health for which there is insufficient 
evidence to undertake an appropriate assessment.  These are:  1. harm of wildlife and the 
environment;123  2. human health risk from outcrossing to wild Brassica species (e.g., Brassica 
cretica) in Greece that are used as food;  3. in creased difficulty in managing farmland because GMHT 
oilseed rape overwinters better in Greece, should spread faster and is  hard to eliminate once 
established as a weed. 
860. In paragraph 821, I suggestted that the first of these is not relevant to Topas 19/2, which is a 
notification for import and processing.  The SCP Opinion states that there is no evidence that the known gene products of the Topas 19/2 tr ansformation are a human health risk,
124 and Greece does 
not address this explicitly.  Thus, there is little meri t in the second risk.  There is some merit in the 
third risk.  On this point there is a clear differen ce in the Opinion of the SCP, which considers this 
remote, and Greece, which does not.  Oilseed rape survives better in Greece than  in France, so while 
this risk is probably very small in France, it is likel y to be larger in Greece.  It is probably fair to 
conclude that it is not certain how much higher this may be.  However, if this risk were substantially 
larger than believed by the SCP, there would many ot her possible ways to manage this risk short of a 
prohibition.   
861. Greece also could have argued in 1998 that ther e was insufficient data to identify all of the 
possible environmental hazards of GMHT oilseed  rape.  (1) Greece could have argued that the 
molecular characterization was insufficient to iden tify all transgene products.  Greece could have 
concluded that there may be risks stemming from these  unidentified transgene products (if they exist) 
that would require a safeguard measure.  It is not clear to me if Topas 19/2 was ever subject to the 
molecular analyses performed for the GM crops evaluated under Directive 2001/18/EC.  (2) Recently 
Greece appears to argue that contamination of conve ntional oilseed rape varieties is an important 
hazard (related to the "coexistence" issue).  This is a hazard that could occur from the small-scale releases expected by accidental spilla ge.  The risk associated with this hazard is probably possible to 
assess now, but I do not have access to the scientific information on the risk management practices 
available to me to make a more certain statement. 
862. Risk 3 (paragraph 859) and such possible hazards as in paragraph 861 would allow Greece to 
argue that there is a risk, and that the risk management measures proposed by the SCP were not 
supported sufficiently by science.125  The scientific evidence in 1998 on the agricultural practices 
necessary to eliminate HT volunteers and wild sp ecies resulting from spillage may not have been 
sufficient to complete an accurate assessment of ri sk management practices.  In addition, Greece may 
have believed that implementing "good" agricultur al practices would be more complicated than 
anticipated by the SCP.  Based on the material in EC-161 and EC-162, I could not determine when 
sufficient information was first available.  The info rmation needed would be s ubstantially less than for 
MS1 x RF1 (questions 59-61).   
                                                      
123 This complaint foreshadows the results from th e UK-FSE trials and models of skylark impact 
124 CDA-63, CDA-73. 
125 This is discussed in more detail in my response to question 59, paragraph 786.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-189 
 
 
  863. Given some of the information provided by Greece and other the information before the 
Panel, Greece could have  argued in November 1998 that there was insufficient evidence to complete a 
risk assessment.  However, I believe that had Greece collected the necessary data to complete this risk 
assessment promptly after implementing their te mporary prohibition that they could have had 
sufficient data to make a decision in 2001. 
Dr. Snow  
864. See ANSWERS 63-65.  I did not find any convincing arguments for why further scientific 
research would be needed to investigate environmen tal effects of a product that is only intended for 
import and processing and not for cultivation.  The specific arguments provided by Greece seem 
flawed.  I do not understand why Greece assumes th at feral populations would become established or 
why they would cause environmental problems.  Even  if such populations become established, there 
is no scientific reason to expect that gene flow coul d harm the genetic diversity or abundance of wild 
relatives of oilseed rape in Greece.  The arguments that Greece made for additional research appear to 
be based on the assumption that the product would be cultivated rather than imported only for processing. 
Question 67:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Greece evaluate the relevant risk s to human, plant or animal health, and the 
environment from the import and pro cessing of oilseed rape Topas 19/2? 
(a) How does the scientific evidence and oth er documentation submitted by Greece 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
865. Environmental issues are not my field, so I cannot judge this point, but all the information for 
the safety assessment of potential risks to human and animal health that was submitted by the 
applicants and evaluated by UK and SCP was adeq uate and in accordance to the Codex Guidelines 
(FAO/WHO Codex Principles for the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants; FAO/WHO Codex Anne x on Possible Allergenicity Assessment). 
Dr. Andow  
866. With reference to the SPS Agreement, Greece has identified one relevant risk to plant 
health.126  In addition, it is also possible to identify ot her relevant risks to plant health.  Specifically, 
in some places Greece did not fully take into account  available scientific evidence, but in others it did 
(Article 5.2).  In addition Greece missed opportun ities to make scientific arguments in its favor. 
867. It is not clear that Greece conducted the risk  assessment according to the phytosanitary 
measures which might be applied.  Greece did not present the safeguard measure as a possible phytosanitary measure, and did not conduct the risk assessment according to this proposed safeguard 
measure.  Thus it is not clear that Greece conduc ted the risk assessment consistent with Annex A, 
paragraph 4. 
                                                      
126 Risk 3, paragraph 859. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-190 
  
  868. Greece did take into account relevant economic factors (Article 5.3), however Greece did not 
explicitly compare the relative cost-effectiveness of alternative approaches to limiting risks. 
869. The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case, because 
Greece did identify a potential risk.  In addition, ot her potential risks relevant to ISPM 11 could be 
identified. 
870. For those risks within the scope of ISPM 11 the risk assessment process is consistent with 
ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
871. It appears that much of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of Greece contradict this guidance.  My reading of the 
materials before the Panel is that Greece did not ex plicitly address this guidance.  Specifically I note 
Section 3, S1 (measures should be designed in proportion to the risk), Section 3.1 (level of acceptable risk should be expressed), Section 3.4 (principle s), and Section 3.4.6 (on prohibition) were not 
explicitly addressed. 
872. The science, documentation and reasoning of Greece are consistent with Annex III of the 
Cartagena Protocol on Biosafety to the Convention on Biological Diversity.  Specifically, Annex III, Section 8(f) states "Where there is uncertainty re garding the level of risk, it may be addressed by 
requesting further information on the specific issues of concern or by implem enting appropriate risk 
management strategies and/or monitoring the living modified organism in the receiving environment." 
Dr. Snow  
873. See ANSWER 66. 
Question 68:  Does the scientific evidence and ot her information submitted by Greece support 
the adoption of a temporary prohibition on the import and processing of oilseed rape Topas 19/2? In light of any potential risks iden tified by Greece, what other risk management 
options were available in September 1998? What other risk management options are now available? 
Dr. Nutti  
874. As far as my knowledge goes, the scientific ev idence submitted by Greece does not support a 
temporary prohibition on the import and processing of oilseed rape Topas 19/2. 
Dr. Andow  
875. Some of the scientific evidence and other information submitted by Greece supports the 
adoption of a temporary prohibition on the import and processing of oilseed rape Topas 19/2.  In 
addition, scientific evidence and other information before the Panel could be used to support the 
adoption of a temporary prohibition on the import and processing of oilseed rape Topas 19/2.  Even on these grounds, the temporary prohibition pr obably could not be justified past 2001. 
876. Several other risk management options could have been justified in November 1998.  Risk 
management strategies include risk avoidance, risk mitigation, and risk tolerance.  In 1998 mitigation and tolerance strategies were proba bly inappropriate.  Another risk avoidance strategy would have 
been to request additional molecular characteriz ation data and allow limited importation with  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-191 
 
 
  attendant monitoring so that the practical aspects of controlling escapes from spillage could 
experienced. 
877. These options were available in 2001 and remain t oday.  In addition risk mitigation strategies 
may also be possible to control HT volunteers and wild species. 
Dr. Snow  
878. See ANSWER 66. 
Maize Bt-176 (notification C/F/11-03)  
Safeguard measure of Austria 
Question 69:  Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-158/at. 1 to 3);  the Scientific Committee for Animal Nutrition in December 1996 (EC-158/At. 4 and 5);  the Scientific Committee for Food in December 1996 (US-64) and in March 1997 (US-58);  the Scientific Commi ttee for Pesticides in December 1996 
(EC-158/At.6_SCI) and in May 1997 (US-57);  the Scientific Committee for Plants (SCP) in 
September 2000 (US-66);  and the European Co mmission in its Decision of January 1997 
(ARG-37), as well as the information submitted by Austria
 with respect to its safeguard 
measure (US-52, EC-158/At.11, 12 and 15; EC-144, EC-147), is there any reason to believe that the scientific evidence available to Austria in Febr uary 1997 was NOT sufficient to permit it to 
undertake an appropriate assessment of potential risks to human, plant and animal health, and the environment from the importation and use of Maize Bt-176?  If so, what scientific evidence 
do you believe was insufficient? 
(a) If the evidence was not sufficient in February 1997, was there sufficient evidence 
available to Austria in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from the importation and use of Maize Bt-176 (EC-158/At.30 to 
42)?  If not, what scientific evidence do you believe was insufficient? 
Dr. Nutti  
879. Answer 69: In EC158-At.04, the Scientific Committee for Animal Nutrition, concludes that 
the probability of the transfer of a functional bl a-gene construct from GM maize to bacteria is 
virtually zero and if this virtually impossible ev ent would take place, it would have no clinical 
significance. The conclusion also pointed out that th ere is no evidence of a risk of causing B-lactam 
antibiotic resistance in animal bacteria with the use of the GM maize. The SCAN opinion was that 
there is no evidence indicating that the use in anim al feeding of the GM maize will give rise to any 
adverse effect on animal health. 
880. In EC158-At. 05, the Scientific Committee for F ood concludes that the GM maize is, except 
for the inserted traits, substantially equivalent to maize present on the market. Animal feeding studies 
support its substantial equivalence to the parent plant. No nutritional concerns are associated with the 
use of this transgenic line; and it is unlikely that the genetic changes introduce any new potential for allergenicity. No human toxicological concerns arise regarding the inserted traits based upon the 
toxicological and degradation data considered.  The conclusion also stated that the possibility that the product would add significantly to the already widesp read occurrence of ampici llin resistant bacteria 
in animals and man is remote and the risk of bacterial transformation is extremely low.  The 
committee recognized the general question of using genes coding for antibiotic resistance for the WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-192 
  
  development of novel foods and propose to scrutinise future needs and applications of this marker 
genes.  In March 1997 (US-58), the Scientific Committee for Food stated that the Austrian 
information does not provide new scientific evidence regarding the food use of Ciba-Geigy maize that 
was not taken into account by the Committee at the time its opinion was delivered. Thus, the Austrian 
information does not cause the SCF to consider that the GM maize constitutes a risk to human health.  
881. In EC158-At. 06_SCI, the Scientific Committee for Pesticides pointed out the glufosinate 
ammonium was not authorized for direct applicatio n into maize plants, and should not, therefore, be 
used for post emergence on genetically modified maize without authorization, in accordance with 
provisions of Directive 91/414/EEC.  As far as the Bt event is concerned, the Scientific Committee for Pesticides was of the opinion that the possible development of insect resistance to the Bt toxin arising from the cultivation of maize plants containing Bt -toxin would not be an adverse effect on the 
environment. 
882. In EC158-At. 07, the Austrian CA informs the applicant that the marketing of Ciba Geigy 
Maize in Austria has been pr ohibited by an ordinance, which entered in force on 14th of February of 
1997, and this action has been in accordance with Art. 16 of Directive 90/220/EEC. The lead CA recognizes that expert from different scientific committees have extensively reviewed and discussed 
problems, concluding the lower risk of the product and all the scientific comments and arguments are valid and well taken, however, from the Austrian poi nt of view, especially new scientific results have 
questioned the present scientific possibility of co nclusive evaluation of the mechanism of gene 
transfer as well as the development of resistance to Bt toxin. 
883. The European Commission, in its Decision of Ja nuary 1997, has given consent to the placing 
on the market of the Ciba Geigy Maize and any proge ny derived from crosses of this product with any 
traditionally bred maize. 
884. Based on the information presented by the notifie rs and by the evaluation of four different 
scientific committees, my understanding is there is NO reason to believe that the scientific evidence 
available to Austria in February 1997 was NOT suffi cient to permit it to undertake an appropriate 
assessment of potential risks to human, plant an d animal health, and the environment from the 
importation and use of Maize Bt-176. 
885. Answer 69a:  In my opinion, the scientific evidence presented was sufficient in 1997 and 
2003.   
Dr. Andow  
886. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
887. The initial assessment of Event 176 by France pr ovided in EC-158/At.1- 3 (10 January 1995, 
1 March 1995, 3 March 1995) does not contain th e details of the assessment by the French 
Biomolecular Engineering Committee (BEC).   
888. The Opinion of the Scientific Committee on Pesticides (EC-158/At.6_SCI, 9 December 1996) 
on Event 176 did not assess the risk of resistance evolution in the target pest s because it considered 
this risk to be an agricultural risk, not an environm ental risk.  In either ev ent, the Committee felt that 
resistance management should be fully considered.  The Committee also did not assess non-target effects.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-193 
 
 
  889. The Opinion of the SCAN (EC-158/At.4, 13 December 1996) did not address any 
environmental risk, including environmentally medi ated indirect effects on animal health.  The 
Opinion of the SCF (US-64, EC-158/At.5, 13 December 1996) did not address any environmental 
risk, including environmentally mediated indirect effects on human health.   
890. On 23 January 1997, the EC decided to allow the placing on the market of Event 176 
(ARG-37). 
891. On 13 February 1997, Austria decided to ban the commercialization of Event 176 in Austria 
(US-52).  Austria gave three reasons for this action.   1. A concern that the risks of the bla gene 
(ampicillin resistance) are greater than that  assessed by the SCAN and the SCF (paragraph 889).  
2. That the Cry1Ab toxin in Event 176 could have ri sks to non-target organisms, including those in 
the soil such as collembola.  3. There is an envi ronmental risk that the target insects will evolve 
resistance to the Cry1Ab toxin, and resistance management measures should be required (they were 
not required by the EC). 
892. In the Further Opinion of the Scientific Co mmittee on Pesticides (US-57, 12 May 1997), "The 
Committee concluded that the reasons and information submitted by the Austrian Authorities did not 
add new relevant evidence to that already cons idered by the Committee and that none of its 
conclusions on the risk to the environment were affected by the Austrian arguments." 
893. The reasoning in the Further Opinion of the Scientific Committee on Pesticides (US-57, 
12 May 1997) is false and did not take into account the scientific information known at the time.  The 
conclusions it reached (paragraph 892) do not follow from the evidence available at the time.   
894. (1) On page 2, the Committee stated that it "recognized the complexity of comparing the 
exposure of a pest to genetically modified plants , where exposure may be prolonged and maintained, 
and conventionally applied pesticides, with shor ter and repeated exposure.  The potential for 
development of resistance could be either accel erated or retarded."  (a) In its 9 December 1996 
Opinion, the Committee nowhere recognized the comple xity of comparing the exposure of a pest to 
genetically modified plants, where exposure may be prolonged and maintain ed, and conventionally 
applied pesticides, with shorter and repeated expos ure.  It must be granted that this is a new 
consideration for the SCP that was introduced by Aust ria.  (b) While it is true that theoretically the 
difference in exposure could result in faster or slow er resistance evolution, the SCP is not discussing a 
theoretical case.  There was more  than adequate data available in 1995 from the notifier's efficacy 
trials (and efficacy trials on Event 176 conducted by public sector scientists) and a long history of 
efficacy trials of Bt insecticide sprays on maize to demonstrate without question that Event 176 would 
exert a selection pressure on corn borers many times stronger (I would estimate ~1000x) than a typical Bt insecticide spray.  The conclusion of th e Committee either is not case-specific and therefore 
inappropriate, or it is case-specific and therefore false. 
895. (2) On page 2, the Committee stated "Based on available information, soil exposure from the 
GMO maize plants will be less than the expo sure resulting from a single conventional spray 
application including the run-off from the plants.  Only trace amounts of toxin can be detected in the roots of the maize and furthermore, normal agricultu ral practice would involve removal of the greater 
part of the plant at harvest.  The plant remains ar e often shredded and transformed into silage for use 
as animal feed at a later stage." (a) In its 9 D ecember 1996 Opinion, the Committee nowhere made the 
assessment that based on available information, so il exposure from the GMO maize plants will be less 
than the exposure resulting from a single conventio nal spray application including the run-off from 
the plants.  Nowhere did the Committee note that th ese issues were addressed satisfactorily in the 
dossier submitted by the notifier.  It must be granted that these considerations are new to the WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-194 
  
                                                       Committee and that they were introduced by Austri a.  (b) The conclusion that soil exposure from the 
Event 176 maize plants will be less than the ex posure from a single Bt spray application was 
debatable even in May 1997.  The Committee did not appear to take into account that nearly all of the 
Cry toxin applied in a Bt spray would be inactivated by sunlight in less than week after spraying.  The 
Committee did not appear to consider that most fa rmers incorporate maize residue into the soil after 
harvest.  This would incorporate several tons of biomass per hectare, putting Cry toxin out of the sun, 
where it could persist for some time.  The Committe e seemed to believe that the maize residue would 
be ensiled.  Silage requires green plant material, and most silage maize is cut while still green, long 
before it would be harvested for grain.  Thus it is not clear that very much residue would be removed 
for silage.  Finally risk assessments should not rely on one study for key conclusions (in this case the 
Palm et al. study, cited as study 4 in the Opin ion).  The SCP assessment should have acknowledged 
that scientific information was scarce at that time, and it would have been better had the SCP 
maintained a more agnostic position with respect to the risk assessment.  Thus, I conclude that the 
Committee did not consider all available scientif ic evidence and did not appropriately weigh 
potentially conflicting information wh en coming to their conclusion. 
896. (3) On page 2-3, the Committee states "The Committee stated in its previous report of 
9 December 1996 that resistance management strate gies are needed during the years of use of any 
pesticide, Bt sprays included.  The Committee drew  attention once again to the need for effective 
resistance management, including monitoring on ag ronomic grounds, to prolong the effectiveness of 
Bt toxin both in conventional sprays and in genetically modified maize.  It also felt that the 
submission of a satisfactory monitoring and r esistance management programme should be a 
requirement for the authorization to use genetically  modified maize seeds expressing Bt-toxin."  (a) In 
its 9 December 1996 Opinion, the Committee nowhere  made the recommendation that the submission 
of a satisfactory monitoring and resistance manage ment programme should be a requirement for the 
authorization to use genetically modified mai ze seeds expressing Bt-toxin.  The acknowledgement 
that it should be a requirement in this 12 May 1997 Opinion is a major change in the conclusions and 
recommendations of the Committee.  It must be gr anted that this change was due to Austria's 
insistence that resistance management measures ar e required for commercial authorization.  (b) The 
Committee does not address Austria's main point on this issue, which is that resistance risk should be 
considered an environmental risk.  The Committee also seems to be unaware of the position of the 
US-EPA in 1996, which was that resistance risk is an environmental risk.127  This is a critical issue 
because it determined whether resistance risk c ould be considered under Directive 90/220/EEC.  
Thus, the Committee did not engage on a critical reason submitted by Austria. 
897. (4) It must be granted that the reasons and information submitted by the Austrian Authorities 
added new relevant evidence that the Scientific Committee on Pesticides had not considered in their 
previous deliberation, and that that a key conclu sion was affected by the Austrian arguments.  
Moreover, the key conclusions by the Committee in this Opinion on non-target risks are overstated 
and/or false. 
898. I conclude that the scientific evidence ava ilable to Austria in February 1997 was NOT 
sufficient to permit it to undertake an appropriate assessment of potential risks to plants and the 
environment from Event 176.  The evidence on risks to non-target organisms, including those in the soil such as collembola was insufficient.  Austria could have mustered sufficient evidence to argue 
that there was an environmental risk that the target insects will evolve resistance to the Cry1Ab toxin, 
and resistance management measures should be re quired.  There was probably insufficient evidence 
 
127 Matten, S.R., et al., The U.S. Environmental Protection Agency's role in pesticide resistance 
management, in Molecular Genetics and Evolution of Pesticide Resistance , T.M. Brown, Ed., American 
Chemical Society, Washington, D.C., 1996, pp. 243-253.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-195 
 
 
                                                       available to determine what measures should be require d.  This determination by Austria was in direct 
contradiction to the EC decision.  In this case, Au stria probably did not then and does not now need to 
claim that their safeguard measure is a precautionary one. 
899. By 2003, the basis for risk assessment of Bt crops had changed because several significant 
scientific points had come to light.  (1) It became  widely appreciated that the molecular basis of 
transformation was more complex than originally th ought, and the implications of these findings for 
risk assessment were articulated.  Annex II of  Directive 2001/18/EC is one consequence, but 
additional regulatory changes have occurred since then.  Indeed, knowledge in molecular biology 
continues to accumulate at remarkably fast rates, an d I expect that there will be continued change in 
regulation in the future.128  (2) Non-target risk assessment shifted from assessing indicators of 
environmental risk to assessing actual identified poten tial environmental risks.  Presently this is done 
on an ad hoc basis, as no systematic methodology h as gained widespread acceptance.  (3) Gene flow 
risk assessment has shifted from being based primarily on an assessment of the probability of gene 
flow to being based on an assessment of both the probability of gene flow and the conditional hazard 
probability.  (4) Resistance risk is considered an environmental risk, and science-based resistance 
management measures are required. 
900. Thus, evidentiary standards for what constitut es an objective environmental risk assessment 
had changed substantially from 1997 to 2003.  This is  particularly true in Europe and the United 
States, and particularly true for the Bt crops.   
901. (1) Thus, in 2003, there remains some uncertainty about non-target risks of Event 176, but it 
could be argued that a risk assessment could be conducted using scientifically justified worst-case 
assumptions.  On the other hand, Austria could reas onably maintain that there is still insufficient 
information to know which non-target species may be at risk, and therefore it is not possible to 
conduct an objective risk assessme nt.  The findings in 2003 by Székács and Darvas (EC-158/At.37) – 
that two protected butterfly species in Hungary, Inac his io and Vanessa atalanta, might be exposed to 
Bt corn pollen and suffer higher mortality – certainly suggests that not all of the non-target species at 
risk to Event 176 have been identified in Europe.  (2) As in 1997, Austria could muster sufficient 
evidence in 2003 to argue that there is an environmental risk that the target insects will evolve resistance to the Cry1Ab toxin in Event 176, and resistance management measures should be required.  
Moreover, in 2003, Austria should have sufficient evidence to determine what kind of resistance 
management measures to require.  (3) Unlike in 1997 , in 2003 Austria could argue that the molecular 
characterization of Event 176 is insufficient to conduct a risk assessment.  (4) In 2004, Austria 
suggested that an additional gene flow risk that  needs assessment is contamination of conventional 
production.  It is possible that the scientific evidence to support risk management measures for this 
risk is available to conduct an objective risk assessment today. 
Question 70:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Austria evaluate the relevant risks to human, plant or animal health, and the environment from the importation and use of Maize Bt-176? 
(a) How does the scientific evidence and oth er documentation submitted by Austria 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
 
128 Possibilities are suggested in Nap et al. 2004. Genomics for Biosafety in Plant Biotechnology . IOS 
Press, NATO Science Series, Amsterdam. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-196 
  
  Dr. Nutti  
902. Answer 70:   Environmental issues are not my field, so I cannot judge this point, but all the 
information for the safety assessment of potential risk s to human and animal health that was submitted 
by the applicants and evaluated by the Scientif ic Committee for Animal Nutrition, the Scientific 
Committee for Food, the Scientific Committee for Pe sticides and the Scientific Committee for Plants 
(SCP) were adequate and in accordance to the Codex Guidelines  (FAO/WHO Codex Principles for 
the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for 
the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants; 
FAO/WHO Codex Annex on Possible Allergenicity Assessment). 
Dr. Andow  
903. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
904. With reference to the SPS Agreement, Austria ha s evaluated relevant risks to plant health.  
Specifically, Austria has taken into account ava ilable scientific evidence (Article 5.2).   
905. It is not clear, however, that Austria conducted the risk assessment according to the 
phytosanitary measures which might be applied.  Austria did not present their safeguard measure as a 
possible phytosanitary measure, and did not conduct the risk assessme nt according to their safeguard 
measure.  Thus it is not clear that Austria conducte d the risk assessment consistent with Annex A, 
paragraph 4. 
906. Austria did take into account relevant economic  factors (Article 5.3), however it did not 
explicitly compare the relative cost-effectiveness of alternative approaches to limiting risks. 
907.  The "potential pest" concept of ISPM 11 must fi rst be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case because 
Austria argues that there is a plant pest risk. 
908. For those risks within the scope of ISPM 11 the risk assessment process is consistent with 
ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
909. It appears that some of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of Austria contradict this guidance.  My reading of the materials before the Panel is that Austria did not explicitly address this guidance.  Specifically I note 
Section 3.4 (principles), and Section 3.4.6 (on prohibition) we re not explicitly addressed.   
910. In US-52, Austria made it clear that they are applying a different standard for acceptable risk 
than reflected in the assessments of the SCAN, SCF, Scientific Committee on Pesticides in the EC 
decision (ARG-37) itself.  In so doing, Austria fulfilled ISPM 11, Section 3.1 (level of acceptable risk should be expressed). 
911. ISPM 11, Section 3.4.6 (prohibition) states "If no satisfactory measure to reduce risk to an 
acceptable level can be found, the final option ma y be to prohibit importation of the relevant 
commodities.  This should be viewed as a measure of last resort and should be considered in light of 
the anticipated efficacy, especially in instan ces where the incentives for illegal import may be 
significant."  With respect to resistance risk, in  1997 Austria had established the existence of an 
environmental risk, and required the development of measures to manage this risk to acceptable  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-197 
 
 
  levels.  As the EC was not willing to make such a requirement, Austria had no choice but to intervene 
with its own safeguard measure.  In 1997, how ever, there was probably insufficient scientific 
evidence to establish what necessary me asures should be taken.  Scientif ically credible suggestions at 
that time focused on using refuges (maize that w as not Bt maize) ranging from 10-70% of the maize 
grown by any farmer who chose to gr ow Bt maize.  It is unlikely th at Austria could have implemented 
any of these suggestions in time for the 1997 growin g season, so I conclude that Austria had fulfilled 
ISPM 11, Section 3.4.6, at least for the 1997 growing season. 
912. The science, documentation and reasoning of Aust ria are consistent with Annex III of the 
Cartagena Protocol on Biosafety to the Convention on Biological Diversity.  Specifically, Annex III, 
Section 8(f) states "Where there is uncertainty re garding the level of risk, it may be addressed by 
requesting further information on the specific issues of concern or by implem enting appropriate risk 
management strategies and/or monitoring the living modified organism in the receiving environment." 
Question 71:  Does the scientific evidence and other information submitted by Austria support 
the adoption of a temporary prohibition on the importation and use of Maize Bt-176?  In light 
of any potential risks identified by Austria, what other risk management options were available in February 1997? What other risk management options are now available? 
Dr. Nutti  
913. It is important to point out that the main issu es raised by Austria were related to the present 
scientific possibility of conclusive evaluation of  the mechanism of gene transfer as well as the 
development of resistance to Bt toxin. As far as my knowledge goes, concerning food safety and nutrition, the scientific evidence submitted by Au stria does not support a temporary prohibition on the 
import and use of Maize Bt-176. 
914. In EC-144, Austrian Contribution for the WTO-Dispute-Expert-Meeting of the  European 
Commission 14 January 2004 in Brussels,  I found th at Austria presents also issues related to 
allergenicity and toxicological ri sk assessment, but I cannot agree with the points raised, as they are 
not in accordance with the FAO/WHO Codex Guide line for the Conduct of Food Safety Assessment 
of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible Allergenicity Assessment.  
Dr. Andow  
915. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
916. The adoption of a temporary prohibition can be ju stified on the basis of the scientific evidence 
and other information submitted by Austria.   
917. Other risk management options could not have been justified in February 1997.  However, 
had Austria worked to develop its own acceptable resistance management measures, perhaps by 1999 
other risk management options would have been possible.  
918. Today several alternative risk management options  are available.  Risk management strategies 
include risk avoidance, risk mitigation, and ri sk tolerance.  Tolerance strategies are probably 
inappropriate.  One alternate risk avoidance st rategy would be to im plement country-specific 
resistance management measures, to limit planting to a restricted region, and to conduct intensive 
non-target experiments.  This would allow progr essive determination of non-target effects.   WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-198 
  
  Safeguard measure of Germany 
Question 72:  Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-158/at. 1 to 3); the Scientific Co mmittee for Animal Nutrition in December 1996 
(EC-158/At. 4 and 5);  the Scientific Committee for Food in December 1996 (US-64) and in 
March 1997 (US-58); the Scientific Committee for Pesticides in December 1996 (EC-158/At.6_SCI) and in May 1997 (US-57); the SCP in September 2000 (US-66); and the European Commission in its Decision of Janua ry 1997 (ARG-37); as well as the information 
submitted by Germany
 with respect to its safeguard measure (US-65, EC-158/At.18-29, 
EC-144), is there any reason to believe that the scientific evidence available to Germany in March 2000 was NOT sufficient to permit it to undertake an appropriate assessment of potential risks to human, plant and animal heal th, and the environment from the importation 
and use of Maize Bt-176? If so, what scienti fic evidence do you believe was insufficient?  
(a) If the evidence was not sufficient in Ma rch 2000, was there sufficient evidence 
available to Germany in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from the importation and use of Maize Bt-176?  If not, what scientific evidence do you believe was insufficient? 
Dr. Nutti  
919. Answer 72:  In US-65 (31/03/2000), the information submitted by Germany with respect to its 
safeguard measure, my understanding is that the CA permits to sell seeds limited to 12 tons per year. The reasons stated by Germany were that harmful effects exist for non-target organisms, development 
of resistance, Bt toxin in the soil and antibiotic r esistant gene, so all points were environment related 
issues.  
920. Environmental issues are not my field, so I cannot judge this point, but all the information for 
the safety assessment of potential risks to human and animal health that was submitted by the 
applicants and evaluated by the Scientific Comm ittee for Animal Nutrition, the Scientific Committee 
for Food, the Scientific Committee for Pesticides and the Scientific Committee for Plants (SCP) were 
adequate and in accordance to the Codex Guide lines (FAO/WHO Codex Principles for the Risk 
Analysis of Foods Derived from Modern Biot echnology; FAO/WHO Codex Guideline for the 
Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO 
Codex Annex on Possible Allergenicity Assessment). 
921. Answer 72a:  In my opinion, the scientific evidence presented was sufficient in 2000 and 
2003, but I can answer only regarding food safety, a nd Germany points were re lated to environmental 
issues.  
Dr. Andow  
922. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
923. The initial assessment of Event 176 by France pr ovided in EC-158/At.1- 3 (10 January 1995, 
1 March 1995, 3 March 1995) does not contain th e details of the assessment by the French 
Biomolecular Engineering Committee (BEC).    WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-199 
 
 
  924. The Opinion of the Scientific Committee on Pesticides (EC-158/At.6_SCI, 9 December 1996) 
on Event 176 did not assess the risk of resistance evolution in the target pest s because it considered 
this risk to be an agricultural risk, not an environm ental risk.  In either ev ent, the Committee felt that 
resistance management should be fully considered.  The Committee also did not assess non-target 
effects. 
925. The Opinion of the SCAN (EC-158/At.4, 13 December 1996) did not address any 
environmental risk, including environmentally medi ated indirect effects on animal health.  The 
Opinion of the SCF (US-64, EC-158/At.5, 13 December 1996) did not address any environmental 
risk, including environmentally mediated indirect effects on human health.   
926. On 23 January 1997, the EC decided to allow the placing on the market of Event 176 
(ARG-37). 
927. Luxembourg (US-63, 7 February 1997) and Aust ria (US-52, 13 February 1997) decided to 
ban the commercialization of Event 176 for r easons covered in questions 69 and 75.   
928. The reasoning in the Further Opinion of the Scientific Committee on Pesticides (US-57, 
12 May 1997) is false and did not ta ke into account the scientific information known at the time.  This 
is fully discussed in my response to question 69, paragraphs 892-897, and will not be repeated here. 
929. In my response to question 69 and question 75, I have concluded that the scientific evidence 
available to Luxembourg and Austria in February 1997 was NOT sufficient to permit them to 
undertake an appropriate assessment of potential risks to plants and the environment from Event 176.   
930. The Regulatory Committee under Directive 90/220/EC met three times to consider Draft 
Commission Decisions to require that the temporary prohibitions by Luxembourg and Austria be repealed.  The first two meetings (EC-158/At.13, 10 November 1997 and EC-158/At.16, 22 January 
1998) resulted in decisions to delay making a deci sion.  The final meeting (EC-158/At/17, 29 April 
1998) resulted in no decision (neither to repeal nor not to repeal). 
931. On 11 November 1997, an Expert Working Group on Bt resistance management was 
launched.  However, I cannot find any of the proceedings of this Working Group in the materials before the Panel. 
932. On 31 March 2000 (US-65), Germany decided to prohibit the unrestricted commercial use of 
Event 176 in Germany.  Germany considered the sci entific information for risk assessment to be 
inadequate in the following areas: effects on non- target organisms, development of resistance, 
countermeasures against development of resistance, effects of Bt toxin in the soil, horizontal or vertical gene transfer of antibiotic resistance ge ne, harm to humans from antibiotic resistance gene. 
933. On 9 November 2000 (US-66), the SCP provided an Opinion on the German decision.  The 
SCP concluded that the scientific information pr ovided by the German Competent Authority does not 
alter the original risk assessments on Event 176.  The Opinion of the SCP is one possible scientific 
opinion that can be reached from the information available at the time, but the SCP should have 
acknowledged that the new information also allows several other scientifically valid opinions that 
were not justifiable in 1996. 
934. On page 3-4 of this Opinion, the SCP deliberates on non-target risks, focusing on three 
organisms, green lacewing, monarch butterfly and bl ack swallowtail.  For the lacewing and monarch, 
the SCP considered the experiments difficult to inte rpret and extrapolate to the field.  It did not WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-200 
  
                                                       interpret the swallowtail case.  Rather than provid e a point by point discussion of the SCP Opinion, I 
will list a series of valid scientific perspectives and interpretations on th e lacewing and monarch 
studies that illustrate some of the diversity of valid  scientific opinion that is not reflected in the SCP 
Opinion.  (1) According to the tiered non-target risk assessment protocols (which are consistent with 
ISPM 11 and Annex III of the Biosafety Protocol and widely used in the US and Europe), the purpose 
of laboratory experiments is to expose the orga nisms to concentrations higher than would be 
considered typical for the field.  By doing so, one  reduces the probability of false negative effects.  
Experimental positives then should undergo additional evaluation.  (2) Both lacewings and monarchs 
were exposed to concentrations of Cry1Ab toxin that  would be expected to be higher than typical for 
the field.  Swallowtails were not exposed to high concentrations.  (3) Both  lacewings and monarchs 
were adversely affected by Cry1Ab toxin in these laboratory experiments.  (4) Additional assessment 
should have been conducted on lacewi ngs and monarchs to determine the relevance to the field.  (5) 
Cry1Ab is supposed to be a toxin specific to mo ths and butterflies, but lacewings are not closely 
related to moths and butterflies.  Hence the toxi city spectrum of Cry1Ab toxin is broader than 
previously expected.  (6) Several years later, it h as been suggested that Event 176 would have caused 
significant risk to monarchs had it become a popularly used variety.129 
935. On page 4 of the Opinion, the SCP delib erates on resistance risk and management, 
considering two organisms, European corn borer an d Mediterranean corn borer.  The SCP advised on 
the establishment of non-Bt refuges adjacent to modifi ed crops but pointed out that, in view of the 
slow introduction into Europe, crops would be surrounded by natural refuges for some time to come.  Rather than provide a point by point discussion of the SCP Opinion, I will list a series of valid scientific perspectives and interpretations that illustrate the prevailing scientific opinion on resistance risk and management in 2000 that is not reflected in the SCP Opinion.  (1) The rate of market 
penetration after initial introduction of Bt maize in th e US was the fastest of any crop variety or crop 
protection technology in the history of US agricultu re.  Prior to introduction, many predicted that 
market penetration would be slow.  They were wr ong.  (2) Resistance evolves locally.  Thus refuges 
must be available wherever Bt-maize is locally u sed.  Thus, refuges need to be required from the 
beginning.  (3) Resistance management is the respons ibility of each farmer who uses Bt maize.  Thus, 
each farmer should be required to implement refuges.  Thus, refuges need to be required from the 
beginning. 
936. On page 5 of the Opinion, the SCP delib erates on toxin release to soil, focusing on 
degradation processes.  The SCP suggests that because  protein turnover occurs routinely in soils and 
degradation of Bt toxin would be e xpected to degrade at rates simila r to other proteins or DNA in the 
soil, there is no evidence that Bt-toxins will persis t in soils and have adve rse effects on non-target 
organisms.  Rather than provide a point by point discussion of the SCP Opinion, I will list a series of 
valid scientific perspectives and inte rpretations that illustrate some of the diversity of valid scientific 
opinion that is not reflected in the SCP Opinion.   (1) The actual rates and degradation processes for 
large proteins in soils is poorly understood.  (2) Bt toxin loading in maize fields during and after 
harvest can be substantial.  Thus, scale effects are pos sible.  (3) Presently it is known that Bt toxin in 
the soil can have an adverse effect on earthworms.  Whether this translates into an actual risk is not 
yet known.   
937. A close reading (paragraphs 934-936) of the SCP Opinion (US-66, 9 November 2000) 
suggests that it has not considered all scientific perspectives (and in some cases ignored prevailing 
scientific opinion).  Thus, the SCP Opinion does not invalidate the scientific opinion of Germany. 
 
129 NRC 2002.  Environmental effects of transgenic plants: The scope and adequacy of regulation.  
National Academy Press, Washington, DC. 320pp.  WT/DS291/R/Add.6 
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 Page H-201 
 
 
                                                       938. I conclude that the scientific evidence available to Germany in March 2000 was NOT 
sufficient to permit it to undertake an appropriate assessment of potential risks to plants and the 
environment from Event 176.  The evidence on risks to non-target organisms, including those in the 
soil could be considered insufficient.  Germany coul d have mustered sufficien t evidence to argue that 
there was an environmental risk that  the target insects will evolve resistance to the Cry1Ab toxin, and 
resistance management measures should be requir ed.  There may have been sufficient evidence 
available to determine what measures should be requi red, but there probably was insufficient evidence 
to determine how to implement these measures effect ively.  This determination by Germany was in 
direct contradiction to the EC decision.  In this  case, Germany probably does not need to claim that 
their safeguard measure is a precautionary one. 
939. By 2003, the basis for risk assessment of Bt crops had changed because several significant 
scientific points had come to light.  (1) It became  widely appreciated that the molecular basis of 
transformation was more complex than originally th ought, and the implications of these findings for 
risk assessment were articulated.  Annex II of  Directive 2001/18/EC is one consequence, but 
additional regulatory changes have occurred since then.  Indeed, knowledge in molecular biology 
continues to accumulate at remarkably fast rates, an d I expect that there will be continued change in 
regulation in the future.130  (2) Non-target risk assessment shifted from assessing indicators of 
environmental risk to assessing actual identified poten tial environmental risks.  Presently this is done 
on an ad hoc basis, as no systematic methodology h as gained widespread acceptance.  (3) Gene flow 
risk assessment has shifted from being based primarily on an assessment of the probability of gene 
flow to being based on an assessment of both the probability of gene flow and the conditional hazard 
probability.  (4) Resistance risk is considered an environmental risk, and science-based resistance 
management measures are required. 
940. Thus, evidentiary standards for what constitut es an objective environmental risk assessment 
had changed substantially from 1997 to 2003.  This is  particularly true in Europe and the United 
States, and particularly true for the Bt crops.   
941. (1) Thus, in 2003, there remains some uncertainty about non-target risks of Event 176, but it 
could be argued that a risk assessment could be conducted using scientifically justified worst-case 
assumptions.  On the other hand, Germany could reas onably maintain that there is still insufficient 
information to know which non-target species may be at risk, and therefore it is not possible to 
conduct an objective risk assessme nt.  The findings in 2003 by Székács and Darvas (EC-158/At.37) – 
that two protected butterfly species in Hungary, Inac his io and Vanessa atalanta, might be exposed to 
Bt corn pollen and suffer higher mortality – certainly suggests that not all of the non-target species at 
risk to Event 176 have been identified in Europe.  (2) As in 1997, Germany could muster sufficient evidence in 2003 to argue that there is an environmental risk that the target insects will evolve 
resistance to the Cry1Ab toxin in Event 176, and resistance management measures should be required.  
Moreover, in 2003, Germany should have sufficien t evidence to determine wh at kind of resistance 
management measures to require.  (3) Unlike in  1997, in 2003 Germany could argue that the 
molecular characterization of Event 176 is insufficien t to conduct a risk assessment.  (4) It is also 
possible for Germany to suggest that an additional gene flow risk that needs assessment is 
contamination of conventional production.  It is po ssible that the scientific evidence to support risk 
management measures for this risk is presently available. 
 
130 Possibilities are suggested in Nap et al. 2004. Genomics for Biosafety in Plant Biotechnology . IOS 
Press, NATO Science Series, Amsterdam. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-202 
  
  Question 73:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Germany evaluate the relevant risk s to human, plant or animal health, and the 
environment from the importation and use of Maize Bt-176? 
(a) How does the scientific evidence a nd other documentation submitted by 
Germany compare with the relevant intern ational guidelines for risk assessment 
and analysis identified above? 
Dr. Nutti  
942. Answer 73:  Environmental issues are not my field, so I cannot judge this point, but all the 
information for the safety assessment of potential risk s to human and animal health that was submitted 
by the applicants and evaluated by the Scientif ic Committee for Animal Nutrition, the Scientific 
Committee for Food, the Scientific Committee for Pe sticides and the Scientific Committee for Plants 
(SCP) was adequate and in accordance to the C odex Guidelines (FAO/WHO Codex Principles for the 
Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for the 
Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible Allergenicity Assessment). 
Dr. Andow  
943. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
944. With reference to the SPS Agreement, Germany h as evaluated relevant risks to plant health.  
Specifically, Germany has taken into account ava ilable scientific evidence (Article 5.2).   
945. It is not clear, however, that Germany cond ucted the risk assessment according to the 
phytosanitary measures which might be applied.  Germany did not present their safeguard measure as 
a possible phytosanitary measure, and did not conduct the risk assessment according to their safeguard 
measure.  Thus it is not clear that Germany conducted the risk assessment consistent with Annex A, paragraph 4. 
946. Germany did not take into account relevant economic factors (Article 5.3). 
947. The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case because 
Germany argues that there is a plant pest risk. 
948. For those risks within the scope of ISPM 11 the risk assessment process is consistent with 
ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
949. It appears that some of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of Germany contradict this guidance.  My reading of the materials before the Panel is that  Germany did not explicitly address this guidance.  Specifically I note 
Section 3.4 (principles), and Section 3.4.6 (on prohibition) we re not explicitly addressed.   
950. In US-65, Germany made it clear in some points that they are applying a different standard 
for acceptable risk than reflected in the assessments of the SCAN, SCF, Scientific Committee on  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-203 
 
 
  Pesticides in the EC decision (ARG-37) itself.  In so doing, Germany fulfilled ISPM 11, Section 3.1 
(level of acceptable risk should be expressed). 
951. ISPM 11, Section 3.4.6 (prohibition) states "If no satisfactory measure to reduce risk to an 
acceptable level can be found, the final option ma y be to prohibit importation of the relevant 
commodities.  This should be viewed as a measure of last resort and should be considered in light of 
the anticipated efficacy, especially in instan ces where the incentives for illegal import may be 
significant."  With respect to resistance risk, in  1997 Austria had established the existence of an 
environmental risk, and required the development of measures to manage this risk to acceptable 
levels.  Germany concurred in 2000.  As the EC  was not willing to make such a requirement, 
Germany had no choice but to intervene with its own safeguard measure.  In 2000, however, there 
was probably sufficient scientific evidence to esta blish what necessary measures should be taken.  
Scientifically credible suggestions at that time fo cused on using refuges (maize  that was not Bt maize) 
ranging from 20-30% of the maize grown by any farmer who chose to grow Bt maize.  It is unlikely 
that Germany could have implemented any of th ese suggestions in time for the 2000 growing season, 
so I conclude that Germany had fulfilled ISPM 11, Section 3.4.6, at least for the 2000 growing season. 
952. The science, documentation and reasoning of Germ any are consistent with Annex III of the 
Cartagena Protocol on Biosafety to the Convention on Biological Diversity.  Specifically, Annex III, 
Section 8(f) states "Where there is uncertainty re garding the level of risk, it may be addressed by 
requesting further information on the specific issues of concern or by implem enting appropriate risk 
management strategies and/or monitoring the living modified organism in the receiving environment." 
Question 74:  Does the scientific evidence and ot her information submitted by Germany support 
the adoption of a temporary prohibition on the importation and use of Maize Bt-176?  In light of any potential risks identified by Germany, what other risk management options were available in March 2000?  What other risk management options are now available? 
Dr. Nutti  
953. It is important to point out that the main issues raised by Germany were that harmful effects 
exist for non-target organisms, development of resist ance, Bt toxin in the so il and antibiotic resistant 
gene, so all points were environmental related issu es. As far as my knowledge goes, regarding  food 
safety and nutrition issues, the scientific evidence submitted by Germany does not support a temporary prohibition on the import and use of Maize Bt-176. 
Dr. Andow  
954. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
955. The adoption of a temporary prohibition (with < 500ha for research purposes) can be justified 
on the basis of the scientific evidence and ot her information submitted by Germany.   
956. Other risk management options could not have been justified in March 2000.  However, had 
Germany worked to develop its own acceptable r esistance management measures, perhaps by 2002 
other risk management options would have been possible.  
957. Today several alternative risk management options may be available.  Risk management 
strategies include risk avoidance, risk mitigation, and risk tolerance.  Tolerance strategies are probably inappropriate.  One alternate risk avoidan ce strategy would be to implement country-specific WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  resistance management measures, to limit planting to a restricted region, and to conduct intensive 
non-target experiments.  This would allow progr essive determination of non-target effects.   
Safeguard measure of Luxembourg 
Question 75:  Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-158/at. 1 to 3); the Scientific Co mmittee for Animal Nutrition in December 1996 
(EC-158/At.4 and 5); the Scientific Committee for Food in December 1996 (US-64) and in 
March 1997 (US-58); the Scientific Committee for Pesticides in December 1996 (EC-158/At.6_SCI) and in May 1997 (US-57); the SCP in September 2000 (US-66); and the 
European Commission in its Decision of Janua ry 1997 (ARG-37), as well as the information 
submitted by Luxembourg
 with respect to its safeguard measure (US-63, EC-158/At.9, EC-144), 
is there any reason to believe that the scientifi c evidence available to Luxembourg in February 
1997 was NOT sufficient to permit it to undertake an appropriate assessment of potential risks 
to human, plant and animal health, and the environment from the importation and use of Maize 
Bt-176?  If so, what scientific evidence do you believe was insufficient? 
(a) If the evidence was not sufficient in February 1997, was there sufficient evidence 
available to Luxembourg in August 2003 to permit it to undertake a more objective assessment of potential risks to human, plant and animal health, and 
the environment from the importation and use of Maize Bt-176?  If not, what scientific evidence do you believe was insufficient?  
Dr. Nutti  
958. Before judging the information submitted by Luxem bourg, it is important to point out that all 
the information for the safety assessment of potential  risks to human and animal health that was 
submitted by the applicants and evaluated by the Scientific Committee for Animal Nutrition, the 
Scientific Committee for Food, the Scientific Committee for Pesticides and the Scientific Committee 
for Plants (SCP) were adequate, and the scientific  opinion of these committees were that the product 
could be planted and consumed in Europe.  
959. In US-63, Ministerial Decree of 7 February 1997 prohibiting the use and sale of a corn 
product obtained by genetic transformation, Minist er of Health, Luxembourg, considering that the 
GM product contains the gene conferring resistance  to ampicillin and that this circumstance risks 
having implication for human health, that in the present state of the dossier cannot be properly evaluated and considering that no monitoring prog ram has been implemented with regard to the 
development of a resistance of the pyralid to the Bt-endotoxin, prohibits the use and sale of the Maize 
Bt-176. 
960. Based on the information presented by the notifie rs and by the evaluation of four different 
scientific committees, my understanding is there is NO reason to believe that the scientific evidence 
available to Luxembourg in February 1997 was NOT sufficient to permit it to undertake an 
appropriate assessment of potential risks to human, plant and animal health, and the environment from 
the importation and use of Maize Bt-176. 
961. Answer 75a:  In my opinion, the scientific evidence presented was sufficient in 1997 and 
2003.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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 Page H-205 
 
 
  Dr. Andow  
962. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks, specifically the resistance monitoring program. 
963. The initial assessment of Event 176 by France pr ovided in EC-158/At.1- 3 (10 January 1995, 
1 March 1995, 3 March 1995) does not contain th e details of the assessment by the French 
Biomolecular Engineering Committee (BEC).   
964. The Opinion of the Scientific Committee on Pesticides (EC-158/At.6_SCI, 9 December 1996) 
on Event 176 did not assess the risk of resistance evolution in the target pest s because it considered 
this risk to be an agricultural risk, not an environm ental risk.  In either ev ent, the Committee felt that 
resistance management should be fully considered.   
965. The Opinion of the SCAN (EC-158/At.4, 13 December 1996) did not address any 
environmental risk, including environmentally medi ated indirect effects on animal health.  The 
Opinion of the SCF (US-64, EC-158/At.5, 13 December 1996) did not address any environmental 
risk, including environmentally mediated indirect effects on human health.   
966. On 23 January 1997, the EC decided to allow the placing on the market of Event 176 
(ARG-37). 
967. On 7 February 1997, Luxembourg decided to ban the commercialization of Event 176 in 
Luxembourg (US-63).  Luxembourg gave  two reasons for this action.  1. A concern that the risks of 
the bla gene (ampicillin resistance) have not b een properly evaluated by the SCAN and the SCF 
(paragraph 965).  2. That a monitoring program must be implemented to monitor the development of 
resistance in the target pest to Cry1Ab toxin in Event 176. 
968. The Further Opinion of the Scientific Comm ittee on Pesticides (US-57, 12 May 1997) is a 
major shift in the position of  the Committee on Event 176. 
969. On page 2-3 of US-57, the Committee states "The Committee stated in its previous report of 
the 9 December 1996 that resistance management st rategies are needed during the years of use of any 
pesticide, Bt sprays included.  The Committee drew  attention once again to the need for effective 
resistance management, including monitoring on ag ronomic grounds, to prolong the effectiveness of 
Bt toxin both in conventional sprays and in genetically modified maize.  It also felt that the 
submission of a satisfactory monitoring and r esistance management programme should be a 
requirement for the authorization to use genetically  modified maize seeds expressing Bt-toxin."  (a) In 
its 9 December 1996 Opinion, the Committee nowhere  made the recommendation that the submission 
of a satisfactory monitoring and resistance manage ment programme should be a requirement for the 
authorization to use genetically modified mai ze seeds expressing Bt-toxin.  The acknowledgement 
that it should be a requirement in this 12 May 1997 Opinion is a major change in the conclusions and 
recommendations of the Committee.  (b) The Committ ee does not address a significant issue implicit 
in Luxembourg's statement, which is that resistance risk should be considered an environmental risk.  
The Committee also seems to be unaware of the position of the US-EPA in 1996, which is that WT/DS291/R/Add.6 
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                                                       resistance risk is an environmental risk.131  This is a critical issue because it determined whether 
resistance risk could be considered under Directive 90/220/EEC.   
970. I conclude that the scientific evidence availa ble to Luxembourg in February 1997 was NOT 
sufficient to permit it to undertake an appropriate assessment of potential risks to plants and the 
environment from Event 176.  Luxembourg could ha ve mustered sufficient evidence to argue that 
there was an environmental risk that the target insects will evolve resistance to the Cry1Ab toxin, 
resistance management measures should be required a nd resistance monitoring is a critical measure.  
There was probably insufficient ev idence available to determine what kind of monitoring should be 
required.  This determination by L uxembourg was in direct contradiction to the EC decision.  In this 
case, Luxembourg probably does not need to claim th at their safeguard measure is a precautionary 
one. 
971. By 2003, the basis for risk assessment of Bt crops had changed because several significant 
scientific points had come to light.  (1) It became  widely appreciated that the molecular basis of 
transformation was more complex than originally th ought, and the implications of these findings for 
risk assessment were articulated.  Annex II of  Directive 2001/18/EC is one consequence, but 
additional regulatory changes have occurred since then.  Indeed, knowledge in molecular biology 
continues to accumulate at remarkably fast rates, an d I expect that there will be continued change in 
regulation in the future.132  (2) Non-target risk assessment shifted from assessing indicators of 
environmental risk to assessing actual identified poten tial environmental risks.  Presently this is done 
on an ad hoc basis, as no systematic methodology h as gained widespread acceptance.  (3) Gene flow 
risk assessment has shifted from being based primarily on an assessment of the probability of gene 
flow to being based on an assessment of both the probability of gene flow and the conditional hazard 
probability.  (4) Resistance risk is considered an environmental risk, and science-based resistance 
management measures are required. 
972. Thus, evidentiary standards for what constitut es an objective environmental risk assessment 
had changed substantially from 1997 to 2003.  This is  particularly true in Europe and the United 
States, and particularly true for the Bt crops.   
973. (1) As in 1997, Luxembourg could muster sufficien t evidence in 2003 to argue that there is an 
environmental risk that the target insects will evolve resistance to the Cry1Ab toxin in Event 176, resistance management measures should be required, and resistance monitoring should be required.  
Moreover, in 2003, Luxembourg probably had sufficient evidence to determine what kind of 
resistance management and monitoring measures to require.  (2) Unlike in 1997, in 2003 Luxembourg 
could argue that the molecular characterization of  Event 176 is insufficient to conduct a risk 
assessment.  (3) Also in 2003, Luxembourg could argue  that an additional gene flow risk that needs 
assessment is contamination of conv entional production.  It is possibl e that the scientific evidence to 
support risk management measures for this risk were available to conduct an objective risk assessment at that time. 
 
131 Matten, S.R., et al., The U.S. Environmental Protection Agency's role in pesticide resistance 
management, in Molecular Genetics and Evolution of Pesticide Resistance , T.M. Brown, Ed., American 
Chemical Society, Washington, D.C., 1996, pp. 243-253. 
132 Possibilities are suggested in Nap et al. 2004. Genomics for Biosafety in Plant Biotechnology . IOS 
Press, NATO Science Series, Amsterdam.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-207 
 
 
  Question 76: With reference to the definition of  a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Luxembourg evaluate the relevant risks to human, plant or animal health, and the 
environment from the importation and use of Maize Bt-176? 
(a) How does the scientific evidence a nd other documentation submitted by 
Luxembourg compare with the relevan t international guidelines for risk 
assessment and analysis identified above? 
Dr. Nutti  
974. Answer 76:  Environmental issues are not my field, so I cannot judge this point, but all the 
information for the safety assessment of potential risk s to human and animal health that was submitted 
by the applicants and evaluated by the Scientif ic Committee for Animal Nutrition, the Scientific 
Committee for Food, the Scientific Committee for Pe sticides and the Scientific Committee for Plants 
(SCP) were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for 
the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for 
the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants; 
FAO/WHO Codex Annex on Possible Allergenicity Assessment). 
Dr. Andow  
975. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks, specifically the resistance monitoring program. 
976. With reference to the SPS Agreement, Luxem bourg has evaluated relevant risks to plant 
health.  However, it is not clear that Luxembourg has taken into account available scientific evidence 
(Article 5.2).  This is not to say that Luxem bourg has not taken into account available scientific 
evidence.   
977. It is not clear that Luxembourg conducted the risk assessment according to the phytosanitary 
measures which might be applied.  Luxembourg did not present their safeguard measure as a possible 
phytosanitary measure.  Luxembourg did not conduct the risk assessment accord ing to their safeguard 
measure.  Thus it is not clear that Luxembourg c onducted the risk assessment consistent with Annex 
A, paragraph 4. 
978. It is not clear that Luxembourg took into account relevant economic factors (Article 5.3).  
This is not to say that Luxembourg has not taken into account relevant economic factors. 
979. The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case because 
Luxembourg argues that there is a plant pest risk. 
980. For those risks within the scope of ISPM 11 the risk assessment process may be consistent 
with ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
981. It appears that much of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of Luxembourg contradict this guidance.  My reading of 
the materials before the Panel is that Luxem bourg did not explicitly address this guidance.  
Specifically I note Section 3, S1 (measures should be  designed in proportion to the risk), Section 3.1 WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-208 
  
  (level of acceptable risk should be expressed), Section 3.4 (principles), and Section 3.4.6 (on 
prohibition) were not explicitly addressed. 
982. The reasoning of Luxembourg is consistent with Annex III of the Cartagena Protocol on 
Biosafety to the Convention on Biological Diversity.  
Question 77:  Does the scientific evidence and other information submitted by Luxembourg 
support the adoption of a temporary prohibitio n on the importation and use of Maize Bt-176?  
In light of any potential risks identified by Luxembourg, what other risk management options 
were available in February 1997? What other risk management options are now available? 
Dr. Nutti  
983. It is important to consider that the main issu es raised by Luxembourg in order to prohibit the 
use and sale of the Maize Bt-176 were that the GM product contains the gene conferring resistance to ampicillin and that this circumstance risks having implication for human heal th, that in the present  
state of the dossier cannot be properly evaluated and that no monitoring program has been 
implemented with regard to the development of a resistance of the pyralid to the Bt-endotoxin. So, 
these are environment related issues. 
984. As far as my knowledge goes, regarding food safety and nutrition issues, the scientific 
evidence submitted by Luxembourg does not support a temporary prohibition on the import and use of 
Maize Bt-176. 
Dr. Andow  
985. In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks, specifically the resistance monitoring program. 
986. The adoption of a temporary prohibition can be ju stified on the basis of the scientific evidence 
and other information available to Luxembourg.  As there are no materi als before the Panel containing 
scientific evidence submitted by Luxembourg, it is  not possible to make a determination of the 
justification for the temporary prohibition based only on submissions from Luxembourg. 
987. Other risk management options probably could not have been justified in February 1997.  
However, Luxembourg could have proposed its  own acceptable resistance monitoring measures, 
which perhaps by 1999 would have been possible to implement.  
988. Today several alternative risk management options  are available for monitoring for resistance.  
Although there is still no scientific consensus around the best monitoring method, the cost-efficiency trade-offs are known, and consider able experience has accumulated so that several can be feasibly 
implemented.   WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-209 
 
 
  Maize MON 810 (notification C/F/95/12-02)  
Safeguard measure of Austria 
Question 78: Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-159/At.1 and 2); and the Scientific  Committee on Plants in February 1998 
(CDA-82), September 1999 (US-55), and September 2000 (CDA-86), and the European 
Commission in its Decision of April 1998 (CDA-81), as well as the information submitted by Austria
 with respect to its safeguard measure (US-54, EC-159/At.4, EC-144, EC-147, EC-148), is 
there any reason to believe that the scientific  evidence available to Austria in June 1999 was 
NOT sufficient to permit it to undertake an appropriate assessment of potential risks to human, plant and animal health, and the environment from Maize MON 810? If so, what scientific evidence do you believe was insufficient?  
(a) If the evidence was not sufficient in June 1999, was there sufficient evidence available to Austria in August 2003
 to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from Maize MON 810 (EC-158/At.30-42)?  If not, what scientific evidence do you believe was insufficient? 
Dr. Nutti  
989. Answer 78:   In EC 159-At 3, Austria informs the applicant that unt il the uncertainties which 
have recently arisen during the review have been definitively clarified, Austria is justified in assuming 
that the cultivation of the product MON810 presents a hazard to human health or the environment. 
The main points presented were related to the undesi red effects on non-target organisms, development 
of resistance in insects, findings regarding the effects of other Bt plants (cotton in Australia and 
USA).  The document calls particular attention to the study carried out at Cornell University on the Bt 
maize N4640Bt produced by Novartis, that sparked fierce reactions within the EU. The European 
Commission, consequently, suspended the authorisation process for the herbicide-tolerant and insect-
resistant CryIA(b) Bt maize MON809 produced by Pioneer.  Austrian CA also informs that no conclusions have yet been reached by the Europ ean Commission regarding the Bt maize plants 
MON810 produced by Monsanto and Bt-176 produced by Novartis, already approved for cultivation 
in the EU.  
990. The Scientific Committee on Plants (SCP) issued  its opinion on the invocation by Austria of 
Article 16 (safeguard clause) of Council Directiv e 90/220/EEc with respect to the placing on the 
market of the GM maize MON 810, and the SCP conclusion was that the information submitted by 
Austria did not constitute new significant information that was not already considered in its original 
risk assessment and maintained the previous ri sk assessment status unchanged. The SCP also 
concluded that this information does not invalidat e its original risk assessments for the other Bt 
products.  I believe the SCP has undertaken a very detailed analysis of the new information and its 
remarks  about the study carried out by Cornell are very detailed, explaining why that study was not conclusive.  I completely agree with the SCP opinion and conclusions. 
991. Based on the information presented by notifiers and by the scientific evaluation undertaken by 
France and by SCP, my understanding is there is no reason to believe that the scientific evidence 
available to Austria in June 1999 was NOT suff icient to permit it to undertake an appropriate 
assessment of potential risks to human, plant an d animal health, and the environment from the 
importation and use of Maize MON 810. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-210 
  
  992. Answer 78a:   In my opinion, the scientific  evidence presented was sufficient in 1999 and 
2003. 
Dr. Andow  
993. My response to this question is the same as my response to question 72, except in the 
following way.  It is apparent from the Commission Decision (CDA-81, 22 April 1998) that resistance 
management and monitoring measures have been proposed  by the notifier.  However, I could not find 
in the materials before the Panel a full descripti on of these resistance management and monitoring 
measures.   
994. The Opinion of the SCP (CDA-82, 10 February 1998) does not provide a full description of 
the proposed resistance management and monitoring measures. 
995. Austria decided to prohibit the unregulated commercial use of Mon810 (EC-159/At.4, 10 
June 1999).  In its explanation for this action, Austria does not provide a full description of the 
proposed resistance management and monitoring measures. 
996. The further Opinion of the SCP (US-55, 24 September 1999) does not provide a full 
description of the proposed resistance management and monitoring measures. 
997. Rather than repeat the arguments in my response to question 72, I summarize as follows.  I 
conclude that the scientific evidence available to Austria in June 1999 was NOT sufficient to permit it 
to undertake an appropriate assessment of potential risks to plants and the environment from Event 
176.  The evidence on risks to non-target organisms,  including those in the soil could be considered 
insufficient.  I cannot provide a scientific judgment about the sufficiency of the scientific evidence on 
resistance management and monitoring, because a full description of these measures is not available 
in the materials before the Panel. 
998. (1) In 2003, there remained some uncertainty about non-target risks of Mon810, but it could 
be argued that a risk assessment could be conducted using scientifically justified worst-case 
assumptions.  On the other hand, Austria could reas onably maintain that there is still insufficient 
information to know which non-target species may be at risk, and therefore it is not possible to 
conduct an objective risk assessme nt.  The findings in 2003 by Székács and Darvas (EC-158/At.37) – 
that two protected butterfly species in Hungary, Inac his io and Vanessa atalanta, might be exposed to 
Bt corn pollen and suffer higher mortality – certainly suggests that not all of the non-target species at 
risk to Mon810 have been identified in Europe.  However, the toxicity of Mon810 pollen had been 
determined not to be high, so it is also possibl e that a worst case risk assessment would have found 
insignificant risk even for these unknown species exposed to pollen.  (2) Unlike in 1999, in 2003 Austria could argue that the molecular characterizati on of Event 176 is insufficient to conduct a risk 
assessment.  (3) In 2004, Austria sugge sted that an additional gene flow  risk that needs assessment is 
contamination of conventional production.  It is po ssible that the scientific evidence to support risk 
management measures is available today.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-211 
 
 
  Question 79:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Austria evaluate the relevant risks to human, plant or animal health, and the 
environment from Maize MON 810? 
(a) How does the scientific evidence and oth er documentation submitted by Austria 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
999. Answer 79:   Environmental issues are not my field, so I cannot judge this point, but all the 
information for the safety assessment of potential risk s to human and animal health that was submitted 
by the applicants and evaluated by the lead CA (France) and the Scientific Committee for Plants 
(SCP) were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for 
the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for 
the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants; 
FAO/WHO Codex Annex on Possible Allergenicity Assessment).  
1000.  The issues raised by Austria were environmental ones.  
Dr. Andow  
1001.  In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
1002.  With reference to the SPS Agreement, Austria ha s evaluated relevant risks to plant health.  
Specifically, Austria has taken into account ava ilable scientific evidence (Article 5.2).   
1003.  It is not clear that Austria conducted the risk assessment according to the phytosanitary 
measures which might be applied.  Austria did not present their safeguard measure as a possible 
phytosanitary measure, and did not conduct the risk assessment according to their safeguard measure.  
Thus it is not clear that Austria conducted the risk  assessment consistent with  Annex A, paragraph 4. 
1004.  It is not clear that Austria took into account relevant economic factors (Article 5.3).  This is 
not to say that it has not taken into account relevant economic factors. 
1005.  The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case because 
Austria argues that there is a plant pest risk. 
1006.  For those risks within the scope of ISPM 11 the risk assessment process is consistent with 
ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
1007.  It appears that much of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of Austria contradict this guidance.  My reading of the materials before the Panel is that Austria did not explicitly address this guidance.  Specifically I note 
Section 3, S1 (measures should be designed in proportion to the risk), Section 3.1 (level of acceptable risk should be expressed), Section 3.4 (principle s), and Section 3.4.6 (on prohibition) were not 
explicitly addressed. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-212 
  
  1008.  The reasoning of Austria is consistent with Annex III of the Cartagena Protocol on Biosafety 
to the Convention on Biological Diversity.  
Question 80:  Does the scientific evidence and other information submitted by Austria support 
the adoption of a temporary prohibition on Maize MON 810?  In light of any potential risks 
identified by Austria, what other risk management options were available in June 1999?  What other risk management options are now available? 
Dr. Nutti  
1009.  Answer 80:   The main issues raised by Austria in order to prohibit the use and sale of the 
Maize MON 810  were related to the undesired e ffects on non-target organisms, development of 
resistance in insects, findings regarding the effects of other Bt plants ( cotton in Australia and USA), 
and these are environmental related issues. 
1010.  As far as my knowledge goes, concerning fo od safety and nutrition issues, the scientific 
evidence submitted by Austria does not support a temporary prohibition of the import and use of 
Maize MON 810. 
Dr. Andow  
1011.  In my response to this question, I will not addr ess issues related to the antibiotic marker gene 
and will focus my remarks on environmental risks. 
1012.  The adoption of a temporary prohibition can be ju stified on the basis of the scientific evidence 
and other information submitted by Austria.   
1013.  Other risk management options may have been  justified in June 1999.  Because the full 
resistance management and monitoring measures were not before the Panel, the scientific basis for a 
concrete discussion of this is not possible.  
1014.  Today several alternative risk management options may be available.  Risk management 
strategies include risk avoidance, risk mitigation, and risk tolerance.  Tolerance strategies are probably inappropriate.  Because the full resistan ce management and monitoring measures were not 
before the Panel, the scientific basis for a concrete discussion of this is not possible. 
Safeguard measure of Italy 
Question 81:  Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-159/At.1 and 2); and the Scientific  Committee on Plants in February 1998 
(CDA-82), September 1999 (US-55), and September 2000 (CDA-86), and the European Commission in its Decision of April 1998 (CDA-81), as well as the information submitted by 
Italy
 with respect to its safeguard measure (EC-157/At.1 and 2, CDA-78), is there any reason to 
believe that the scientific evidence available to Italy in August 1988 was NOT sufficient to 
permit it to undertake an appropriate assessment of potential risks to human, plant and animal 
health, and the environment from Maize MON 810 ? If so, what scientific evidence do you 
believe was insufficient? 
(a) If the evidence was not sufficient in August 1988, was there sufficient evidence 
available to Italy in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-213 
 
 
  environment from Maize MON 810?  If not, what scientific evidence do you 
believe was insufficient? 
Dr. Nutti  
1015.  Answer 81:   At EC 157-At.01, the Italian CA  considers illegal the procedure for the placing 
on the market of certain transgenic foodstuffs , namely BT11 MAIZE, MON810 MAIZE, and MS1 
RF1, MS1 RF2 and GT-73 rapeseed oil, MON 809 MAIZE and T25 MAIZE, considering illegal 
because the condition of "substan tial equivalence" to existing e quivalent foodstuffs required by 
Article 3, Paragraph 4, of EC Regulation No 258/ 97 is not met.  This document also points the 
ambiguity of the term "substantial equivalence", that  in the opinion of the Italian CA, this concept 
could be defined differently, given the lack of cl arity in the Community legislation. The lead CA 
informs that considering that the Superior Institute of Health, in its opinion, pointed out that, of the 
seven notified products cited above, the four types of maize contain levels of protein deriving from 
the genetic modifications ranging from 0.04 to 30 pa rts per million and that; therefore, the foodstuff 
has been permanently affected by  the modified elements. The lead Ca does not agree with the 
technical documentation provided, as far as the co mparison of the GMOs and their conventional 
counterpart is concerned.  The document informs that the Superior Institute of Health also came to the 
conclusion that, in the light of current scientific know ledge, there are no apparent risks to the health of 
humans or livestock from the consumption of derivati ves of the aforementioned GMOs, but the Italian 
CA believes that there are inade quacies in the risk assessment procedures. The document also points 
that the Superior Institute of Health declines to express an opinion regarding the risk of possible 
"environmental release" of the GMOs in question. 
1016.  The Scientific Committee on Plants in February 1998 (CDA-82), after examining and 
considering the existing information and data provide d in the dossier, considered that there was no 
evidence to indicate that the seed s of GM maize MON810, when grown, imported and processed in 
the manner indicated, are likely to cause adverse effects on human or animal health and the environment.  
1017.  The Scientific Committee on Plants, in Febr uary September 1999 (US-55), concludes that 
there is no new evidence that would change its  previous assessment of GM maize MON 810. 
1018.  The Scientific Committee on Food, in Se ptember 2000 (CDA-86), presents its opinion 
concerning the submission from the Italian authorities raising concerns from the safety of certain 
products approved under the notification procedure of Regulation (EC) 258/97, concluding that the 
information provided by the Italian Authorities does not provide detailed scientific grounds for 
considering the use of the novel foods in question endangers human health.  
1019.  The European Commission Decision of 22 April 1998 gives consent for placing on the market 
the inbred lines derived from maize line MON 81 0 and any progeny derived from crosses of the 
product with any traditionally bred maize. 
1020.  My opinion is that the Italian CA did not provi de any scientific information that could change 
the evaluations done by the scientific committees (Food a nd Plant). It is important to point out that the 
information submitted by the applicant, covered all the items needed for the comparison of the GM 
maize and its conventional counterpart, not only with  data on nutrients but also with animal feeding 
studies.  The variation in levels of protein was in the range of natural variation, so the point raised by Italy referring to protein was not correct. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-214 
  
  1021.   I do not agree with opinion of the Italian CA regarding the ambiguity of  the term "substantial 
equivalence", that, this concept could be define d differently, given the lack of clarity in the 
Community legislation.  The way to proceed fo r the comparison between the GM and non GM has 
been presented not only at the Community legislati on but also at the OECD consensus documents, 
FAO/WHO Expert Consultations 1996, 200, 200 1 and Codex Alimentarius Guidelines.  
1022.  My understanding is there is NO reason to belie ve that the scientific evidence available to 
Italy in August 1988 was NOT sufficient to perm it it to undertake an appropriate assessment of 
potential risks to human, plant and animal health , and the environment from e of Maize MON 810.  
1023.  Answer 81a:   In my opinion, the scientific  evidence presented was sufficient in 1998 and 
2003. 
Question 82: With reference to the definition of  a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Italy evaluate the relevant risk s to human, plant or animal health, and the 
environment from Maize MON 810? 
(a) How does the scientific evidence and other documentation submitted by Italy 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
1024.  Answer 82:   All the information for the safet y assessment of potential risks to human and 
animal health that was submitted by the applicants  and evaluated by the lead CA (France) and the 
Scientific Committee for Plants (SCP) and Scientific Committee for Foods  were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Code x Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible 
Allergenicity Assessment). 
1025.  Answer 82a: The information and arguments pr ovided by Italy were not in accordance with 
FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants, paragraphs 44 , 45, 48. 
Question 83: Does the scientific evidence and ot her information submitted by Italy support 
the adoption of a temporary prohibition on Maize MON 810?  In light of any potential risks identified by Austria, what other risk management options were available in August 1988? 
What other risk management options are now available? 
Dr. Nutti  
1026.  Answer 83: The scientific evidence submitted by  Italy do not support a temporary prohibition 
of Maize MON 810.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-215 
 
 
  Maize T25 (notification C/F/95/12-07)  
Safeguard measure of Austria 
Question 84:  Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-160/At.1 and 2); the SCP in September 2000 (CDA-75) and September 2001 
(CDA-86 and CDA-77), and the European Commission in its Decision of April 1998 (CDA-74), 
as well as the information submitted by Austria  with respect to its safeguard measure (EC-
160/At.3 and 5, CDA-76, EC-144, EC-153), is there any reason to believe that the scientific evidence available to Austria in April 2000 was NOT sufficient to permit it to undertake an 
appropriate assessment of potential risks to human, plant and animal health, and the environment from Maize T25? If so, what scienti fic evidence do you believe was insufficient?  
(a) If the evidence was not sufficient in Ap ril 2000, was there sufficient evidence 
available to Austria in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from Maize T25 (EC-158/At.30-42)?  If not, what scientific evidence do you believe was insufficient? 
Dr. Nutti  
1027.  Answer 84: In EC160 At.03, the Austrian CA pr ohibits the Maize T25, informing that this 
event has not been examined under realistic cond itions of the use of this herbicide and of 
correspondent agricultural practice.  Neither the notification seeking approval of the placing on the 
market T25 nor the decision of the European Co mmission is foreseeing a m onitoring programme.  It 
is emphasized that special measures for monitoring the possible spread of pollen  to the fields in the 
surrounding cultivated with conventional maize is missi ng, and the lack of this monitoring program is 
crucial.  The document also call attention to regiona l ecological aspects that are not differentiated and 
the need for further investigations of eventual long term, also secondary, ecological effects. 
1028.  The SCP, in September 2000 (CDA-75), has consid ered that there was no evidence to indicate 
that the use of the GM maize T25 as any other maiz e, is likely to cause adverse effects on human or 
animal health and the environment. 
1029.  The SCP, in September 2001 (CDA-77), gave its opinion on the invocation by Austria of 
Article 16 of Council Directive 99/22/EEC, regarding the GM maize T25, concluding that the 
information submitted by Austria did not provide ne w scientific information to change the original 
risk assessment carried out on the GM maize T25. 
1030.  The European Commission Decision of 22 April 1998 gives consent for placing on the market 
the inbred lines derived from maize line T25 an d any progeny derived from crosses of the product 
with any traditionally bred maize. 
1031.  Based on the information presented by the notifiers and by the scientific evaluation 
undertaken by France and by the SCP, my understanding is there is NO reason to believe that the scientific evidence available to Austria in June 19 99 was NOT sufficient to permit it to undertake an 
appropriate assessment of potential risks to human, plant and animal health, and the environment from 
the GM maize T25. 
1032.  Answer 84a: In my opinion, the scientific evidence presented was sufficient in 2000 and 
2003. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-216 
  
  Dr. Andow  
1033.  The reasons for Austria's safeguard measure are provided by Austria (CDA-76, EC-160/At.3, 
20 April 2000).  While the exact statement (unofficial translation) is reproduced below, there are 6 
reasons stated.  (1) The environmental risks of  T25 have not been sufficiently evaluated under 
realistic conditions.  (2) There is no post-comme rcialization monitoring program.  (3) Although harm 
from pollen transfer to conventional maize production fi elds is likely absent, the potential for this risk 
should be monitored.  (4) There is no provision fo r the protection of ecologically sensitive regions.  
(5) There is a need for regionally differentiated "good farming practice" guidelines to minimize the danger of resistance.  (6) There is a need to assess long-term and secondary ecological effects. 
The maize line T25 had not been examined  under realistic conditions of the use of 
this herbicide and of correspondent agricu ltural practice.  Neither the notification 
seeking approval of the placing on the market of T25 nor the decision of the 
European Commission are foreseeing a monitoring programme. 
Furthermore special measures monitoring the possible – mostly regarded as safe – spread of pollen to fields in the surroundi ngs cultivated with conventional maize are 
missing. 
The lack of a monitoring programme regarding long-term effects of genetically modified plants or herbicides can be criticized especially because of the fact that the approval conditions are not foreseeing a protection of sensitive areas (Hoppichler J., 
Expert Innenbefragung zur Bewertung und Evaluation, "GVO-freier ökologisch 
sensibler Gebiete", Study on behalf of the Austrian Federal Chancellery, Vienna, 
1999). 
Furthermore regional ecological aspects are not differentiated:  the use of herbicide resistant plants in areas of unavoidable appli cations of herbicides seems to be useful, 
if the good agricultural practice minimizes the danger of a resistance development. 
Under other ecological – respectively agricu ltural – conditions the use of herbicide 
resistant plants such as maize should only ta ke place after further investigations of 
eventual long-term – also secondary – ecological effects. 
1034.  Regarding these reasons, (1) is possible grounds for the safeguard measure.  (2) is a risk 
management measure and must be justified by refe rence to a risk.  Austria does not reference any 
particular risk, so this cannot be grounds for the safeguard measure.  (3) is a possible grounds for the 
safeguard measure.  (4) is a risk management measur e and must be justified by reference to a risk.  
Austria does not reference any particular risk, so this cannot be grounds for the safeguard measure.  
(5)  Austria provides no argument that region-specifi c guidelines are necessary even when the risk of 
resistance is regionally differentiated.  Regarding th e risk of resistance, Austria has not differentiated 
between the risk associated with volunteers and the risk associated with the evolution of resistance in weeds.  There is no scientific ground for resistance risk associated with maize volunteers in Europe.  Thus the only possible ground for the safeguard measure is the risk of resistance evolution in weeds.  
(6) presents a class of risks that are possible gr ounds for the safeguard measure.  Thus, I will 
concentrate on the following four reasons – (1) The environmental risks of T25 have not been sufficiently evaluated under realistic conditions ; (3) Although harm from pollen transfer to 
conventional maize production fields is likely absent, the potential for this risk should be monitored; 
the specified part of (5), viz., resistance risk in weeds, and (6) There is a need to assess long-term and secondary ecological effects – as possible grounds for the safeguard measure.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-217 
 
 
                                                       1035.  Regarding (6), long-term effects are certainly possible, but it is difficult to assess long-term 
effects in pre-commercial risk assessments.  In othe r words, risks that do manifest on long-term time 
scales are difficult to predict, and unknown long-term effects must be managed after the fact.  Thus, 
the lack of long-term assessments of unknown effect s cannot be considered a reason for the safeguard 
measure.  As no long-term effects have been iden tified beyond resistance risk, this part of (6) cannot 
be used to justify the safeguard measure.  The remaining part of (6), secondary ecological effects, is a 
specific case of reason (1) and will be treated together with (1). 
1036.  Regarding (3), Austria has acknowledged that th e possible harm is likely absent, but does not 
specify concretely the possible harm.  It is  obvious that Austria cannot be thinking about 
contamination of conventional produc tion (related to the "coexistence" issue) at this time.  If it had 
considered this, it would not acknowledge that the possible harm is likely absent.  As the amended SCP Opinion (CDA-77, 20 July 2001) also does not specific a possible harm, it is difficult to see how 
this reason can justify the safeguard measure. 
1037.  Regarding (1), the amended SCP Opinion (CDA-77, 20 July 2001) does not provide an 
assessment of environmental risks beyond gene flow risks.  These would include non-target and other biodiversity risks.  However, Austria does not pr ovide any scientific eviden ce that such risks may 
exist for T25 maize.  A risk assessment cannot be co nsidered insufficient if all concrete possible risks 
are addressed.  In this respect (1) cannot be  used to justify the safeguard measure.  
1038.  This leaves only resistance ri sk in weeds as the only possible grounds for the safeguard 
measure.  The amended SCP Opinion (CDA-77, 20 July  2001) does not provide an assessment of this 
environmental risk.  Even though Austria did not provided any scientific evidence that this risk exists 
for T25 maize, resistance risks are widely recognized, and the consistent use of glufosinate with T25 maize would result in a resistance risk.  Thus, there was insufficient scientific  evidence available to 
the SCP and Austria to assess weed resistance risk  and appropriate risk management measures. 
1039.  Managing resistance risk in maize should be easi er than managing resistance risk in oilseed 
rape, so I would expect that adequate information for a risk assessment could have been made available by 2003, had the parties made c oncerted efforts to bring it together. 
1040.  However, as I have stated repeatedly, the evidentiary standards for what constitutes an 
objective environmental risk assessment had changed substantially from 1997 to 2003.  While this has been particularly true for the Bt crops, there has also be a shift for GMHT crops.  (1) It became widely 
appreciated that the molecular basis of transforma tion was more complex than originally thought, and 
the implications of these findings for risk asse ssment were articulated.  Annex II of Directive 
2001/18/EC is one consequence, but additional regulatory changes have  occurred since then.  Indeed, 
knowledge in molecular biology contin ues to accumulate at remarkably fast rates, and I expect that 
there will be continued change in regulation in the future.
133  (2) The UK-FSE trials have indicated 
that there are possible risks to biodiversity associat ed with herbicide use on GMHT crops.  However, 
for GMHT maize, no adverse effects were found.   (3) Contamination of conventional production 
(related to the "coexisitence" issue) is a new issue that could be new grounds for the safeguard 
measure.  It is possible, however, that the scien tific evidence to support risk management measures 
for this risk to conventional maize were available in 2003.  Thus, in 2003, Austria could also argue 
that T25 was inadequately characterized. 
 
133 Possibilities are suggested in Nap et al. 2004. Genomics for Biosafety in Plant Biotechnology . IOS 
Press, NATO Science Series, Amsterdam. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-218 
  
  Question 85:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Austria evaluate the relevant risks to human, plant or animal health, and the 
environment from Maize T25? 
(a) How does the scientific evidence and oth er documentation submitted by Austria 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
1041.  Answer 85: Environmental issues are not my field, so I cannot judge this point, but all the 
information for the safety assessment of potential risk s to human and animal health that was submitted 
by the applicants and evaluated by the lead CA (France) and the Scientific Committee for Plants 
(SCP) were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for 
the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Codex Guideline for 
the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants; 
FAO/WHO Codex Annex on Possible Allergenicity Assessment).  
1042.  The issues raised by Austria are environment related.  
Dr. Andow  
1043.  With reference to the SPS Agreement, Austria h as evaluated a risk relevant to plant health.  
However, it is not clear that Austria has taken into account available scientific evidence (Article 5.2). 
1044.  It is not clear that Austria conducted the risk assessment according to the phytosanitary 
measures which might be applied.  Austria did not present their safeguard measure as a possible 
phytosanitary measure, and did not conduct the risk assessment according to their safeguard measure.  
Thus it is not clear that Austria conducted the risk  assessment consistent with  Annex A, paragraph 4. 
1045.  Austria did not take into account rele vant economic factors (Article 5.3). 
1046.  The "potential pest" concept of ISPM 11 must first be considered.  This is a special case of 
the general argument in my response to question 6,  and that argument holds for this case because 
Austria argues that there is a plant pest risk. 
1047.  For those risks within the scope of ISPM 11 the risk assessment process is consistent with 
ISPM 11.  However, the economic assessments called for in ISPM 11 were not conducted.   
1048.  It appears that much of the ISPM 11 guidance on risk management has not been followed.  
However, this is not to imply that the actions of Austria contradict this guidance.  My reading of the materials before the Panel is that Austria did not explicitly address this guidance.  Specifically I note 
Section 3, S1 (measures should be designed in proportion to the risk), Section 3.1 (level of acceptable risk should be expressed), Section 3.4 (principle s), and Section 3.4.6 (on prohibition) were not 
explicitly addressed. 
1049.  There is prima facie evidence that Austria did not follow Section 3, S1 (measures in 
proportion to risk).  Resistance risk a long-term ri sk.  Austria probably could have phased in a series 
of measures that would have allowed planting, but guar ded against resistance risk.  It is not clear that 
a prohibition is in proportion to the risk.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-219 
 
 
  1050.  The reasoning of Austria is probably consistent  with Annex III of the Cartagena Protocol on 
Biosafety to the Convention on Biological Divers ity.  However, Austria provided little in science 
documentation to conclude that this  was consistent with Annex III. 
Question 86:  Does the scientific evidence and other information submitted by Austria support 
the adoption of a temporary prohibition on Maize T25?  In light of any potential risks identified by Austria, what other risk management opti ons were available in April 2000? What other risk 
management options are now available? 
Dr. Nutti  
1051.  Answer 86: As far as my knowledge goes, re garding food safety and nutrition issues, the 
scientific evidence submitted by Austria do not support a temporary prohibition on GM maize T25. 
Dr. Andow  
1052.  The adoption of a temporary prohibition was probably not justified on the basis of the 
scientific evidence and other information submitted by Au stria.  Austria needed to clarify the rationale 
and provide substantial scientific evidence.  A temporary prohibition probably could have been 
justified at the time because the appropr iate scientific information did exist. 
1053.  Several other risk management options could al so have been justified in April 2000.  Risk 
management strategies include risk avoidance, risk mitigation, and risk tolerance.  In 2000 mitigation and tolerance strategies were probabl y inappropriate.  Here I consider only the resistance risk.  One 
risk avoidance strategy would have been to allow limited planting in a restricted region.  This would 
allow observing how T25 would be used and enable  assessment of the selective pressure on weeds.  
Another approach would have been to limit use on any particular field to once every 4-5 years.  This 
would reduce selection pressure for a long time, al lowing alternative management measures to be 
developed. 
1054.  Today the same measures are available.  
Safeguard measure of Italy 
Question 87:  Given the information before the Pa nel, including the evaluations undertaken by 
France (EC-160/At.1 and 2);  the SCP in September 2000 (CDA-75) and September 2001 (CDA-
86 and CDA-77), and the European Commission in its Decision of April 1998 (CDA-74), as well as the information submitted by Italy
 with respect to its safeguard measure (CDA-78, EC-
157/At.1 and 2), is there any reason to believe that the scientific evidence available to Italy in 
August 1988 was NOT sufficient to permit it  to undertake an appropriate assessment of 
potential risks to human, plant and animal health, and the environment from Maize T25?  If so, 
what scientific evidence do you believe was insufficient? 
(a) If the evidence was not sufficient in August 1988, was there sufficient evidence 
available to Italy in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from Maize T25? If not, what  scientific evidence do you believe was 
insufficient? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-220 
  
  Dr. Nutti  
1055.  Answer 87:  In EC 157-At.01 and CDA 78, the Italian CA considers illegal the procedure for 
the placing on the market of certain transgenic foodstuffs, namely BT11 MAIZE, MON810 MAIZE, 
and MS1 RF1, MS1 RF2 and GT-73 rapeseed oil,  MON809 MAIZE and T25 MAIZE, considering 
illegal because the condition of "subs tantial equivalence" to existing equivalent foodstuffs required by 
Article 3, Paragraph 4, of EC Regulation No 258/ 97 is not met.  This document also points the 
ambiguity of the term "substantial equivalence", that  in the opinion of the Italian CA, this concept 
could be defined differently, given the lack of cl arity in the Community legislation. The lead CA 
informs that considering that the Superior Institute of Health, in its opinion, pointed out that, of the 
seven notified products cited above, the four types of maize contain levels of protein deriving from 
the genetic modifications ranging from 0.04 to 30 pa rts per million and that; therefore, the foodstuff 
has been permanently affected by the modified elements.  The lead Ca does not agree with the 
technical documentation provided, as far as the co mparison of the GMOs and their conventional 
counterpart is concerned.  The document informs that the Superior Institute of Health also came to the 
conclusion that, in the light of current scientific know ledge, there are no apparent risks to the health of 
humans or livestock from the consumption of derivati ves of the aforementioned GMOs, but the Italian 
CA believes that there are inadequacies in the risk  assessment procedures.  The document also points 
out that the Superior Institute of Health declines to express an opinion regarding the risk of possible 
"environmental release" of the GMOs in question. 
1056.  The SCP, in September 2000 (CDA-75), has consid ered that there was no evidence to indicate 
that the use of the GM maize T25 as any other maiz e, is likely to cause adverse effects on human or 
animal health and the environment. 
1057.  The Scientific Committee on Food, in Se ptember 2000 (CDA-86), presents its opinion 
concerning the submission from the Italian authorities raising concerns from the safety of certain 
products approved under the notification procedure of Regulation (EC) 258/97, concluding that the 
information provided by the Italian Authorities does not provide detailed scientific grounds for 
considering the use of the novel foods in question endangers human health.  
1058.  My opinion is that the Italian CA did not provi de any scientific information that could change 
the evaluations done by the scientific committees (Food a nd Plant).  It is important to point out that 
the information submitted by the applicant covered a ll the items needed for the comparison of the GM 
maize and its conventional counterpart, not only with  data on nutrient but also with animal feeding 
studies.  The variation in levels of protein was in the range of natural variation, so the point raised by 
Italy referring to protein was not correct. 
1059.   I do not agree with opinion of the Italian CA regarding the ambiguity of  the term "substantial 
equivalence", that this concept could be defined differently, given the lack of clarity in the 
Community legislation.  The way to proceed fo r the comparison between the GM and non GM has 
been presented not only at the Community legislati on but also at the OECD consensus documents, 
FAO/WHO Expert Consultations 1996, 200, 2001 and the Codex Alimentarius Guidelines.  
1060.  My understanding is there is NO reason to belie ve that the scientific evidence available to 
Italy in August 1988 was NOT sufficient to perm it it to undertake an appropriate assessment of 
potential risks to human, plant and animal health, and the environment from GM maize T25.  
1061.  Answer 87a: In my opinion, the scientific evidence presented was sufficient in 1998 and 
2003.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-221 
 
 
  Question 88:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Italy evaluate the relevant risk s to human, plant or animal health, and the 
environment from Maize T25? 
(a) How does the scientific evidence and other documentation submitted by Italy 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
1062.  Answer 88:  All the information for the safe ty assessment of potential risks to human and 
animal health that was submitted by the applicants  and evaluated by the lead CA (France) and the 
Scientific Committee for Plants (SCP) and Scientific Committee for Foods were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Code x Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible Allergenicity Assessmen..)  
1063.  Answer 88a: The information and arguments pr ovided by Italy were not in accordance with 
FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants, paragraphs 44 , 45, 48. 
Question 89:  Does the scientific evidence and other information submitted by Italy support the 
adoption of a temporary prohibition on Maize T25? In light of any potential risks identified by 
Italy, what other risk management options were available in August 1988? What other risk management options are now available? 
Dr. Nutti  
1064.  Answer 89:  The scientific evidence subm itted by Italy does not support a temporary 
prohibition on GM Maize T25. 
Maize MON 809 (notification C/F/95/12-01/B)  
Safeguard measure of Italy 
Question 90:  Given the information before the Pa nel, including the evaluations undertaken by 
the Scientific Committee on Plants in M ay 1998 and September 2000 (CDA-85 and CDA-86), as 
well as the information submitted by Italy  with respect to its safeguard measure (CDA-78, EC-
157/At.1 and 2), is there any reason to believe that the scientific evidence available to Italy in August 1988 was NOT sufficient to permit it  to undertake an appropriate assessment of 
potential risks to human, plant and animal health, and the environment from Maize MON 809?  If so, what scientific evidence do you believe was insufficient? 
(a) If the evidence was not sufficient in August 1988, was there sufficient evidence 
available to Italy in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from Maize MON 809? If not,  what scientific evidence do you 
believe was insufficient? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
WT/DS293/R/Add.6 
Page H-222 
  
  Dr. Nutti  
1065.  Answer 90: The  SCP, in May 1998 (CDA-85), h as considered that there was no evidence to 
indicate that the seeds of the GM MON809 and proge ny derived thereof, when grown, imported and 
processed in the manner indicated, are likely to cau se adverse effects on human and the environment. 
1066.  In EC 157-At.01 and CDA 78, the Italian CA c onsiders illegal the procedure for the placing 
on the market of certain transgenic foodstuffs , namely BT11 MAIZE, MON810 MAIZE, and MS1 
RF1, MS1 RF2 and GT-73 rapeseed oil, MON 809 MAIZE and T25 MAIZE, considering illegal 
because the condition of "substan tial equivalence" to existing e quivalent foodstuffs required by 
Article 3, Paragraph 4, of EC Regulation No 258/ 97 is not met.  This document also points the 
ambiguity of the term "substantial equivalence", that  in the opinion of the Italian CA, this concept 
could be defined differently, given the lack of clar ity in the Community legislation.  The lead CA 
informs that considering that the Superior Institute of Health, in its opinion, pointed out that, of the 
seven notified products cited above, the four types of maize contain levels of protein deriving from 
the genetic modifications ranging from 0.04 to 30 pa rts per million and that; therefore, the foodstuff 
has been permanently affected by the modified elements.  The lead Ca does not agree with the 
technical documentation provided, as far as the co mparison of the GMOs and their conventional 
counterpart is concerned.  The document informs that the Superior Institute of Health also came to the 
conclusion that, in the light of current scientific know ledge, there are no apparent risks to the health of 
humans or livestock from the consumption of derivati ves of the aforementioned GMOs, but the Italian 
CA believes that there are inadequacies in the risk  assessment procedures.  The document also points 
that the Superior Institute of Health declines to express an opinion regarding the risk of possible "environmental release" of the GMOs in question. 
1067.  The Scientific Committee on Food, in Se ptember 2000 (CDA-86), presents its opinion 
concerning the submission from the Italian authorities raising concerns from the safety of certain 
products approved under the notification procedure of Regulation (EC) 258/97, concluding that the 
information provided by the Italian Authorities does not provide detailed scientific grounds for 
considering the use of the novel foods in question endangers human health.  
1068.  My opinion is that the Italian CA did not provi de any scientific information that could change 
the evaluations done by the scientific committees (Food a nd Plant). It is important to point out that the 
information submitted by the applicant, covered all the items needed for the comparison of the GM 
maize and its conventional counterpart, not only with  data on nutrient but also with animal feeding 
studies. The variation in levels of protein was in the range of natural variation, so the point raised by 
Italy referring to protein was not correct. 
1069.   I do not agree with the opinion of the Italian CA regarding the ambiguity of the term 
"substantial equivalence", that this  concept could be defined differently, given the lack of clarity in 
the Community legislation. The way to proceed fo r the comparison between the GM and non GM has 
been presented not only at the Community legislati on but also at the OECD consensus documents, 
FAO/WHO Expert Consultations 1996, 200, 2001 and the Codex Alimentarius Guidelines.  
1070.  My understanding is there is NO reason to belie ve that the scientific evidence available to 
Italy in August 1988 was NOT sufficient to perm it it to undertake an appropriate assessment of 
potential risks to human, plant and animal health , and the environment from GM maize MON 809.  
1071.  Answer 90a: In my opinion, the scientific evidence presented was sufficient in 1998 and 
2003.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-223 
 
 
  Question 91:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Italy evaluate the relevant risk s to human, plant or animal health, and the 
environment from Maize MON 809?  
(a) How does the scientific evidence and other documentation submitted by Italy 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
1072.  Answer 91: All the information for the safety assessment of potential risks to human and 
animal health that was submitted by the applicants  and evaluated by the lead CA (France) and the 
Scientific Committee for Plants (SCP) and Scientific Committee for Foods  were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Code x Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible Allergenicity Assessment). 
1073.  Answer 91a: The information and arguments pr ovided by Italy were not in accordance with 
FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants, paragraphs 44, 45, 48. 
Question 92:  Does the scientific evidence and other information submitted by Italy support the 
adoption of a temporary prohibition on Maize MON 809? In light of any potential risks 
identified by Italy, what other risk management options were available in August 1988? What other risk management options are now available? 
Dr. Nutti  
1074.  Answer 92: The scientific evidence submitted by Italy does not support a temporary 
prohibition of GM Maize MON 809. 
Maize Bt-11 (reference C/GB/96/M4/1)  
Safeguard measure of Italy 
Question 93:  Given the information before the Pa nel, including the evaluations undertaken by 
Great Britain (EC-163(At.1 to 3), the Scientific  Committee on Plants in February 1998 (CDA-
83), November 2000 (CDA-84), and April 2002 (CDA-35-J), and the European Commission in 
its Decision of April 1998 (CDA-80), as we ll as the information submitted by Italy  with respect 
to its safeguard measure (CDA-78, EC-157/At. 1 a nd 2), is there any reason to believe that the 
scientific evidence available to Italy in August 1988 was NOT sufficient to permit it to undertake 
an appropriate assessment of potential risks to human, plant and animal health, and the 
environment from Maize Bt-11? If so, what scientific evidence do you believe was insufficient?  
(a) If the evidence was not sufficient in August 1988, was there sufficient evidence 
available to Italy in August 2003  to permit it to undertake a more objective 
assessment of potential risks to huma n, plant and animal health, and the 
environment from Maize Bt-11?  If not, what scientific evidence do you believe was insufficient? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  Dr. Nutti  
1075.  Answer 93: The SCP, in February 1998 (CDA-83), has considered that the import of 
genetically modified seed (notification C/GB/96/M4 /1) carrying the Bt11 event can be considered as 
safe as utilising seed from non-genetically modified plants. 
1076.  In EC 157-At.01 and CDA 78, the Italian CA c onsiders illegal the procedure for the placing 
on the market of certain transgenic foodstuffs , namely BT11 MAIZE, MON810 MAIZE, and MS1 
RF1, MS1 RF2 and GT-73 rapeseed oil, MON 809 MAIZE and T25 MAIZE, considering illegal 
because the condition of "substan tial equivalence" to existing e quivalent foodstuffs required by 
Article 3, Paragraph 4, of EC Regulation No 258/ 97 is not met.  This document also points the 
ambiguity of the term "substantial equivalence", that  in the opinion of the Italian CA, this concept 
could be defined differently, given the lack of cl arity in the Community legislation. The lead CA 
informs that considering that the Superior Institute of Health, in its opinion, pointed out that, of the 
seven notified products cited above, the four types of maize contain levels of protein deriving from 
the genetic modifications ranging from 0.04 to 30 pa rts per million and that; therefore, the foodstuff 
has been permanently affected by  the modified elements. The lead Ca does not agree with the 
technical documentation provided, as far as the co mparison of the GMOs and their conventional 
counterpart is concerned.  The document informs that the Superior Institute of Health also came to the 
conclusion that, in the light of current scientific know ledge, there are no apparent risks to the health of 
humans or livestock from the consumption of derivati ves of the aforementioned GMOs, but the Italian 
CA believes that there are inade quacies in the risk assessment procedures. The document also points 
that the Superior Institute of Health declines to express an opinion regarding the risk of possible "environmental release" of the GMOs in question. 
1077.  The Scientific Committee on Food, in Se ptember 2000 (CDA-86), presents its opinion 
concerning the submission from the Italian authorities raising concerns from the safety of certain 
products approved under the notification procedure of Regulation (EC) 258/97, concluding that the 
information provided by the Italian Authorities does not provide detailed scientific grounds for 
considering the use of the novel foods in question endangers human health.  
1078.  The SCP, in November 2000 (CDA-84), considered that there was no evidence to indicate 
that placing on the market for cultivation purposes of maize line Bt-11 and varieties derived from this 
line by conventional crosses between Bt11 line and maize lines other than genetically modified ones, 
was likely to cause any adverse effects on human health and the environment. 
1079.  The Scientific Committee on Food, in Apr il 2002 (CDA-35-J), presents its opinion on a 
request to place on the market GM maize Bt-11, an d concludes that Bt-11 sweet maize is as safe for 
human food use as its conventional counterparts. In  this document, at item 3.4.2 – Compositional 
Analysis, the Committee presents a detailed evaluati on of the data presented by the applicants and 
concludes that  the one case in which the content of crude protein of the transformed kernel was 
significant lower than the isogenic control sample, no statistical differences have been observed and 
concludes Bt-11 sweet maize kernels are substantia lly equivalent to a non-transformed lines except 
for the new traits or proteins. In item 3.10 – Nutr itional Evaluation, the Committee concludes that the 
Gm Bt-11, with respect to nutritional evaluation, is substantially equivale nt to non-modified maize 
hybrids. In item 3.12.2 – Toxicological data on th e Cry1A(b) protein, the Committee refers to the 
gastric and intestinal fluid tests, oral toxicologi cal tests and resistance to trypsin. Animal feeding 
studies were also evaluated and no adverse effects were seen in these studies. I completely agree with 
the Scientific Committee on Food, and my understandi ng is that the applicant has conducted all the 
tests that were necessary for the safety assessment of the Bt-11.  WT/DS291/R/Add.6 
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  1080.  My opinion is that the Italian CA did not provi de any scientific information that could change 
the evaluations done by the scientific committees (Food a nd Plant). It is important to point out that the 
information submitted by the applicant covered all the items needed for the comparison of the GM 
maize and its conventional counterpart, not only with  data on nutrient but also with animal feeding 
studies. The variation in levels of protein was not st atically significant, so the point raised by Italy 
referring to protein was not correct. 
1081.  I do not agree with the opinion of the Italian CA regarding the ambiguity of the term 
"substantial equivalence", that this  concept could be defined differently, given the lack of clarity in 
the Community legislation. The way to proceed fo r the comparison between the GM and non GM has 
been presented not only at the Community legislati on but also at the OECD consensus documents, 
FAO/WHO Expert Consultations 1996, 200, 2001 and the Codex Alimentarius Guidelines.  
1082.  My understanding is there is NO reason to belie ve that the scientific evidence available to 
Italy in August 1988 was NOT sufficient to perm it it to undertake an appropriate assessment of 
potential risks to human, plant and animal health, and the environment from GM maize Bt 11. 
1083.  Answer 93a: In my opinion, the scientific evidence presented was sufficient in 1998 and 
2003. 
Question 94:  With reference to the definition of a risk assessment in the SPS Agreement (see 
Background above), to what extent does the scientific evidence and other documentation 
submitted by Italy evaluate the relevant risk s to human, plant or animal health, and the 
environment from Maize Bt-11?  
(a) How does the scientific evidence and other documentation submitted by Italy 
compare with the relevant internationa l guidelines for risk assessment and 
analysis identified above? 
Dr. Nutti  
1084.  Answer 94: All the information for the safety assessment of potential risks to human and 
animal health that was submitted by the applicants and evaluated by the lead CA (Great Britain) and the Scientific Committee for Plants (SCP) and Scientific Committee for Foods were adequate and in accordance to the Codex Guidelines (FAO/WHO Codex Principles for the Risk Analysis of Foods Derived from Modern Biotechnology; FAO/WHO Code x Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Plants; FAO/WHO Codex Annex on Possible 
Allergenicity Assessmet).) 
1085.  Answer 94a:  The information and arguments pr ovided by Italy were not in accordance with 
FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants, paragraphs 44, 45, 48. 
Question 95:  Does the scientific evidence and other information submitted by Italy support the adoption of a temporary prohibition on Maize Bt- 11?  In light of any potential risks identified 
by Italy, what other risk management options were available in August 1988?  What other risk 
management options are now available? WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  Dr. Nutti  
1086.   Answer 95: The scientific  evidence submitted by Italy does not support a temporary 
prohibition on GM Maize Bt-11. 
ISSUE 3  
Background : The following questions have the objective of assisting the Panel to determine 
whether, for the specific biotech products at issue in this dispute, there are significant differences in 
the risks arising to human, plant or animal health, or to the environment, from the consumption and 
use of those products and: 
(a) the consumption and use of those biotech products approved by th e European Communities 
prior to October 1998, taking into account the sci entific evidence available at the time of such 
approvals; 
 
(b) the consumption and use of comparable novel  non-biotech products (s uch as plant products 
produced by selective breeding, cross-breeding and mutagenesis)  for consumption as food or 
for planting or processing use;  and 
 
(c) the consumption and use of foods produced with biotech processing aids, including yeasts, 
bacteria or enzymes that have been modified using recombinant DNA technology. 
 
The experts are not being asked to judge the absolute significance of any differences, but to identify whether differences exist and if so, to what extent, and to assist the Panel to understand the nature 
and significance of any differences. 
 
Furthermore, where there are no significant differen ces in the potential risks, the objective of the 
questions is to assist the Panel to determine whether there are scientific or technical reasons for managing any potential risks from the biotech products  at issue in this dispute in a different manner 
than other products (eg., monitoring requirements , agricultural management practices, etc.). 
 
With regard to these questions, the experts may wish to comment on the replies by the Parties to the 
questions by the Panel, in particular the rep lies to questions 23–26 and 29–32 (replies submitted 
16 June 2004). 
 
Questions:  
Products of biotechnology approved by th e European Communities prior to October 1998 
Question 96:  Has there been a significant chan ge in the understanding of physical, chemical 
and biological characteristics of biotech products, gene interactions, gene expression, gene silencing, molecular characterization, and product specific detection since 1998? 
Dr. Nutti  
1087.  Answer 96: I will not judge any environmental issu e, since this is not my area of expertise. 
However, in the areas of food safety, human and an imal nutrition, toxicology and allergenicity, the 
same approach has been used since 1996 to assess the safety of GM products (FAO/WHO Expert 
Consultation, 1996).  The evolution of the safety assessm ent process in the last ten years is very much 
related to the research (which generated a vast bibliography on the subject), discussion and public  WT/DS291/R/Add.6 
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  perception/awareness developed during the peri od, when OECD produced several consensus 
documents and the Codex Alimentarius approved the guidelines for the safety assessment of GM 
plants and microorganisms. Also, a lot of resear ch has been conducted in different countries 
(Australia, New Zealand, Japan, USA, European Union etc), in order to improve the whole process. Nowadays, although we have in use (in all steps of the safety assessment) techniques which are more 
refined, the approach remains essentially the same , fact which is clearly presented in the Codex 
Alimentarius guidelines.  
Dr. Squire  
1088.  From this reviewer's perspective, most of the underlying molecular and biochemical 
knowledge of the subject has not changed substantia lly during this period. There is still uncertainty 
over unintended side-effects occurring in biotech products, and the continued stability of phenotype in biotech plants or continued expression of their gene s outwith the crop itself (i.e. in volunteers and 
feral plants).  
Question 97:  On the basis of the information be fore the Panel, is there new scientific evidence 
since 1998 that would suggest that the potential risk s to human, plant or animal health, or to the 
environment, from any of the specific biotech products subject to this dispute (including products subject to the member State safegu ard measures), are different in nature or 
magnitude as compared to the scientific understandi ng of the risks associated with such biotech 
products prior to 1998, taking into account: 
• the intended use of each product (direct human or animal consumption, further processing for consumption, planting or any other specified use); 
• any potential risks that may arise from the combination or successive use of biotech products.  
Does the information before the Panel support th e view that the potential risks from the 
products in this dispute should be assessed differently than the risks from biotech products approved prior to 1998?  
Dr. Nutti  
1089.  Answer 97:  My opinion is that, based on the existing literature and knowledge on the subject, 
and from a scientific perspective, there is no new evidence that would suggest that the potential risks 
to human, animal or plant health, from any of the sp ecific biotech products subject to this dispute, are 
different in nature or magnitude as compared to those products of biotechnology approved by the 
European Communities prior to October 1998.  
1090.  I will not judge any environmental issue, since this is not my area of expertise. However, in 
the areas of food safety, human and animal nutrition,  toxicology and allergenicity, the same approach 
has been used since 1996 to assess the safety of GM products (FAO/WHO Expert Consultation, 
1996).  The evolution of the safety assessment process in  the last ten years is very much related to the 
research (which generated a vast bibliogr aphy on the subject), discussion and public 
perception/awareness developed during the peri od, when OECD produced several consensus 
documents and the Codex Alimentarius approved the guidelines for the safety assessment of GM plants and microorganisms. Also, a lot of resear ch has been conducted in different countries 
(Australia, New Zealand, Japan, USA, European Uni on etc), in order to improve the whole process.  
Nowadays, although we have in use (in all steps of the safety assessment) techniques which are more WT/DS291/R/Add.6 
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  refined, the approach remains essentially the same , fact which is clearly presented in the Codex 
Alimentarius guidelines. 
1091.  According to the WHO document "20 Questions on Genetically Modified Foods", available at 
http://www.who.int/foodsafety/publications/biotech/en/20questions_en.pdf , the GM foods currently 
available on the international market have passed risk assessments and are not likely to present risks 
for human health. In addition, no effects on human  health have been shown as a result of the 
consumption of such foods by general population in  the countries where they have been approved. 
Continuous use of risk assessments based on the Codex principles and, where appropriate, including 
post market monitoring, should form the basis for evaluating the safety of GM foods. 
Dr. Andow  
Changes since 1998 : 
1092.  The main changes that have occurred since 1998 are related to risk assessment methodologies 
and the evidence needed in a risk  assessment.  There are some di fferences between the transgenic 
crops evaluated and approved before 1998 by the EC  and those evaluated later, but these differences 
are not as great as the changes in risk assessment methodologies and evidence needed.  These changes 
came about from increased scientific  knowledge about transgenic crops.  This has affected risk 
assessment for transgenic crops intended for planting in  the environment.  Scientific investigation of 
risks of combination biotech products has lagged behind. 
1093.  As I indicated in previous answers, the basi s for risk assessment of transgenic crops had 
changed because several significant scientific points had come to light.  (1) It became widely 
appreciated that the molecular basis of transforma tion was more complex than originally thought, and 
the implications of these findings for risk assessment we re articulated.  (2) Non-target risk assessment 
shifted from assessing indicators of environmental risk to assessing actual identified potential environmental risks.  Presently this is done on an ad hoc basis, as no systematic methodology has 
gained widespread acceptance.  (3 ) Gene flow risk assessment has shifted from being based primarily 
on an assessment of the probability of gene flow  to being based on an assessment of both the 
probability of gene flow a nd the conditional hazard probability.  (4 ) Resistance risk is considered an 
environmental risk, and science-based resistance management measures are required. 
1094.  Thus, risk assessment methodologies and eviden tiary standards for what constitutes an 
objective environmental risk assessment had cha nged substantially from 1998 to 2005.  This is 
particularly true in Europe and the United States, and particularly true for the Bt crops.   
1095.  Below, I will sketch some of the changes in non-target risk assessment and resistance risk 
assessment and management.   
Non-target risk assessment : 
1096.  Through 1997, most studies on non-target and biodi versity risks of transgenic plants showed 
no effect of the transgenic plant (Fitt et al. 1994; Sims 1995; Dogan et al. 1996; Orr & Landis 1997; Pilcher et al. 1997; Yu et al. 1997; EPA 2001; Monsanto Company 2002a, b).  The methodological approach used in nearly all of the studies wa s an indicator species approach similar to the 
ecotoxicological assessments of pesticides where indi cator species are used to extrapolate to risks in 
the actual environment.  Only one laboratory study showed a lower survival of the springtail Folsomia 
candida (Willem) when fed with high concentrations  of Bt corn leaf protein (EPA 2001), but the 
significance of this result is not clear.  These indicat or species are not usually closely associated with  WT/DS291/R/Add.6 
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  the transgenic plant tested or the area where the plants are grow n.  Based on these studies, many 
scientists believed that non-targets were not significantly at risk. 
1097.  In 1998, studies by Hilbeck et al (1998a,b) invigorated consideration of non-target risks by 
reporting an unexpected adverse effect of Bt corn on the predatory green lacewing Chrysoperla carnea 
Stephens.  They fed C. carnea larvae with Cry1Ab Bt corn-fed prey or a diet containing purified 
Cry1Ab toxin, and found higher immature mortality compared to controls.  These results were surprising because the Cry1Ab toxin is believed to be Lepidopteran-specific, while C. carnea belongs 
to the Neuroptera, an order that is more closely related to the Coleoptera than to the mecopteroid 
orders including the Lepidoptera.  These results have been confirme d by additional studies (Hilbeck et 
al. 1999; Dutton et al. 2002; Dutton et al. 2003), although the mechanism is still uncertain.  These 
studies suggested that Cry toxins may be l ess specific than previously believed.  
1098.  In the years following 1998, publications on no n-target risks began to shift from indicator 
species to the actual (or tangible) potential risks on species that naturally occur in areas where 
transgenic plants are meant to be cultivated.  In  early 1999, Losey et al. (1999) suggested that 
monarch larvae (Danaus plexippus L.) suffered highe r mortality when feeding on their primary host 
plant, the common milkweed Asclepias syriaca L., dus ted with transgenic Cry1Ab Bt pollen.  This 
initial observation was later confirmed by Jesse & Obrycki (2000) and coupled with the realization that ~50% of the monarch breeding habitat is lo cated in the Corn Belt (Wassenaar & Hobson 1998), 
this triggered concerns that large-scale cultivation of Bt corn would harm the monarch population.  
Monarch butterflies attract wide interest in the US  for multiple reasons, such as their beauty, iconic 
significance to the public, and spectacular migration ove r several thousand miles.  Stimulated by these 
results, a group of researchers conducted a series of studies to estimate the actual risk of Bt corn to 
monarch butterflies (Hellmich et al. 2001; Oberhauser et al. 2001; Pleasants et al. 2001; Sears et al. 
2001; Stanley-Horn et al. 2001; Zangerl et al. 2001).  Sears et al. (2001) concluded that the risk to 
monarch populations was insignificant, and in an excellent review, Oberhauser & Rivers (2003) 
summarized the events and finding s associated with these studies.  Recent studies (Anderson et al. 
2004; Jesse & Obrycki 2004; Dively et al. 2004), however, have revealed a higher toxicity of Bt 
pollen and anthers than found in previous studies.  Although Dively et al. (2004) suggested that the 
risk to monarchs remains insignificant, a close anal ysis of the issues may allow other interpretations 
of risk to monarchs.   
1099.  This shift to considering tangible risks may ha ve helped identify potential adverse effects to 
the Federally endangered Karner blue butterfly (Lycaeides melissa samuelis Nabokov, Lepidoptera, 
Lyceanidae).  Instead of focusing  only on commercial corn fiel ds, dispersal of pollen and the 
production of corn in wildlife refuges could expose this endangered species to Bt pollen.  The 2000 Scientific Advisory Panel (SAP) of the US E nvironmental Protection Ag ency (EPA) acknowledged 
the possibility that this species ma y come in contact with Bt pollen (see also Andow et al. 1995), and 
the EPA (2001) required additional assessment of the risks to Karner Blue butterfly. 
1100.  During 1999, research oriented toward assessing the tangible potential risks associated with 
soils was published.  Saxena et al. (1999) found th at Cry1Ab is released into the soil via corn root 
exudates, where it can persist for at least 350 days (Saxena et al. 2002).  These results suggested that 
Bt corn could possibly affect rhizosphere and so il communities.  Later, Zwahlen et al. (2003a) 
reported that the Cry1Ab toxin in Bt corn litter pers isted for at least 8 months. Together these studies 
showed that long-term exposure of soil organisms to Bt toxins was possible and that the risks of Bt 
crops on soil ecosystem functioning should be assessed.  Zwahlen et al. (2003b) also showed that mortality and weight development of adult and juve nile earthworms, Lumbricus terrestris L., were not 
significantly different when fed Bt or non-Bt corn  residues, with the exception that after 200 days, 
adult Bt corn-fed earthworms had a significant wei ght loss compared to the non-Bt corn-fed ones.   WT/DS291/R/Add.6 
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  1101.  Non-target risks associated with herbicide-to lerant crops were hardly studied until 2000, 
when Watkinson et al. (2000) suggested that these cr ops might adversely effect skylark populations in 
the UK.  A large-scale field evaluation of herbicide-tolerant crops in the UK was established to 
investigate possible actual effects on non-target speci es, and results were published in 2003.  For the 
most part, ecological effects propagated from whatev er changes in the weed community that resulted 
from the change in herbicide use.  The non-target e ffects of herbicide tolerant crops have not been 
studied intensively elsewhere.  
1102.  In 2004, Andow & Hilbeck (2004) presented the outline of a new risk assessment model for 
non-target effects of transgenic crops.  Implicitly they are proposing to systematize the actual/ 
tangible risk assessment process th at has been building since 1999.  An important innovation is to 
select locally occurring non-target species that are mo st likely to be exposed to a transgenic crop and 
likely to make significant contributions to the eco logical functioning of the local ecosystem.   
1103.  Non-target and biodiversity risk assessments of tr ansgenic plants continue to be improved.  
While indicator species continue to be used in many risk assessments, there is a trend towards 
assessing actual/ tangible risks involving species that naturally occur in areas where transgenic crops will be planted.  In the future it will continue to  be important to assess not only the effects of the 
transgenic plant itself but also the effects associated with chang es in agricultural practices.  In 
addition, although they may be difficult to develop and verify, effective methods for biodiversity 
assessment have not yet been developed.   
Resistance risk assessment and management : 
1104.  The evolution of pest resistance to pest control measures has been known for nearly 100 
years, but it became a significant problem after World War II, when modern, intensive agricultural 
technologies proliferated, resulting in strong uniform selection over large areas.  About 536 species of arthropods, 60 genera of plant pathogenic fungi, and 174 weed species have evolved resistance to 
pesticides (Eckert 1988; WeedScience.org 2003; Whalon et al. 2004), and resistance to Bt toxins has 
been documented in >17 insect species (Tabashnik 1994, Huang et al. 1999).  Interestingly, virologists remain unconvinced that resistance will evolve to transgenic virus resistant crops (Tepfer 2002), however, despite some disagreement (reviewed  in Tabashnik 1994), entomologists and weed 
scientists agree that resistance evolution is a real  risk for which some management is desirable 
(NRC 1986).   
1105.  At the beginning of the 1990s, it had proven di fficult to implement effective resistance 
management for most pesticides.  Indeed, there was pessimism that a high-dose/ refuge resistance management system could ever be implemented for insecticide resistance management because a high dose could not be reliably maintained (Roush 1989; Tabashnik 1989).  With the advent of transgenic Bt crops, hopes were renewed (Gould 1994; Roush 1994) , but it was not clear that a high-dose/ refuge 
strategy would delay resistance enough with a reasonably sized refuge (Comins 1977).   
1106.  In a series of simple simulations based on Comins (1977) early work, Alstad & Andow 
(1995) showed that the high-dose/ refuge strategy c ould delay resistance in European corn borer to Bt 
corn for more than 30 years with a 50% non-Bt co rn refuge.  Subsequent research suggested that 
smaller refuges would also substantially dela y resistance, proving that effective resistance 
management was possible theoretically (Gould 1998; Shelton et al. 2000). 
1107.  The focus shifted to practicalities.  Could an effective resistance management strategy be 
implemented?  In the US, this question was answer ed through a series of decisions made by the EPA.  
In early 1995, the EPA registered Bt potato, and although resistance risk was recognized, no  WT/DS291/R/Add.6 
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  resistance management was required. By the end of  that year, EPA issued conditional registrations 
and required the development of resistance manageme nt for all subsequent Bt crops (Matten et al. 
1996).  Conditional registrations were used to mo tivate the development and implementation of a 
scientifically justified resistance management strategy.   
1108.  The key issues in 1995 were how large a refuge  was needed, did the refuge need to be 
spatially structured relative to the Bt fields, and could the refuge be managed to limit pest losses?  
Aspects of some of these questions remain unresolved  today.  In Australia, Bt cotton did not provide a 
high-dose against the key pest, cotton bollworm Helicoverpa armigera (Hübner), and growers and 
researchers agreed to require 70% refuges to make the likelihood of resistance remote (Fitt 1997).  In 
the US, Bt cotton provided a high-dose against the key pest, cotton budworm Heliothis virescens (F.), but not against another important pest, Helicoverp a zea (Boddie), however, refuge requirements were 
set at 4% unsprayed or 20% sprayed refuge outside of the Bt field with minimal requirements of spatial structure.  In 2001, spatial structure requi rements were added for Bt cotton along with other 
modifications.  These initial requirements and changes represent a compromise among various 
interests, although science played a significant role.   
1109.  Resistance management requirements for Bt corn  developed with strong scientific input.  
Early in 1997, the USDA regional research committee NC-205 reviewed model results and 
information on the ecology of European corn borer and suggested to registra nts and the EPA that a 
20-25% refuge was needed near all Bt corn fiel ds (Anon. 1998).  Research results supporting this 
recommendation were published in the ensuing y ears (Onstad & Gould 1998; Hunt et al. 2001; 
Bourguet et al. 2003).  One of the key results was a bioeconomic model suggesting that a 20% refuge 
would be nearly optimal for growers who consider the trade-off between the immediate costs of the 
refuge and delayed costs of resistance failures (H urley et al. 2001).  Canada required a 20% refuge 
within 0.5 miles (~800 meters) of Bt corn in 1998, and during 1999 a consensus was reached in the 
US and the EPA required a 20% refuge within 0.5 miles of Bt corn for the 2000 growing season and 
thereafter.   
1110.  Several scientific issues remain unresolved.  Understanding the mechanisms of resistance is 
necessary to tailor resistance management to the par ticular system, but these are just beginning to be 
revealed for Bt crops (Gahan et al. 2001).  The details of adult movement may play a key role in the 
evolution of resistance (Caprio 2001; Ives & Andow 2002).  Limited dispersal of adults from natal 
fields (Comins 1977), pre- versus  post-mating adult movement, and male versus female movement 
(Ives & Andow 2002) may have significant effects on m odels of resistance evolution, and estimating 
these movement rates in the field is challenging.  Farming practices, such as crop rotation (Peck & Ellner 1997), management of the refuge (Onsta d et al. 2002; Ives & Andow 2002), and rational 
approaches to pest management, may affect the rates of resistance evolution.  Significantly, a 
consensus for managing low-dose events  has yet to emerge, and scientific analysis of this problem is 
incomplete.  For example, Australia implemented 70% refuges for one low-dose event, while the US 
has used 20% refuges for both high- and low-dose events.   
1111.  Monitoring for the occurrence and frequency of resistance and methods to improve 
compliance to resistance management requirements among growers are areas of current research.  The 
key monitoring problem is how to estimate resistance when it is rare and recessive.  One promising approach is the F
2 screen (Andow & Alstad 1998; Andow & Ives 2002; Stodola & Andow 2004).  It is 
a genic screen and works by inbreeding isofemale lines so that recessive phenotypes are expressed in 
the F 2 generation, when they can be screened.  If mated females are collected from natural 
populations, each carries four haplotypes (two of her own and two of her mate's ) and only 250 female 
lines need to be screened instead of 106 field-collected individuals.  The F 2 screen has been used for 
several species (Bentur et al. 2000, Bourguet et al. 2003; Génissel et al. 2003).  Other genetic and WT/DS291/R/Add.6 
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                                                       phenotypic methods have been used on some cotton pests (Gould et al. 1997; Tabashnik et al. 2000), 
but usually phenotypic screens will have lower sensi tivity and higher cost than genic screens (Andow 
& Ives 2002).  Improving compliance will require a combination of bioeconomic modeling, surveys 
of grower behavior and motivations, and development of eff ective educational materials. 
1112.  Our understanding of resistance risk and manageme nt continues to evolve.  Presently, none of 
the Bt crops now used has suffered a resistance failure  despite widespread use.  While this may be due 
to good fortune, in some cases, such as Bt cotton in  Australia, resistance management must have been 
crucial to avoiding failure, and in other cases, such as Bt cotton in Arizona, US, other factors must also be important (Tabashnik et al. 2003).  Interes tingly, relatively little research has focused on weed 
resistance to herbicides used with  the herbicide tolerant crops.  This problem has been treated as a 
theoretical herbicide resistance problem (Gressell et al. 1996), but with recent reports of weed 
resistance (WeedScience.org 2003), this may change.
134 
 
134 References by Dr. Andow: 
 
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Hilbeck, A., Moar, W.J., Pusztai-Carey, M., Filippini, A. & Bigler, F.  (1999) .  Prey-mediated effects 
of Cry1Ab toxin and protoxin and Cry2A protoxin on the predator Chrysoperla carnea. Entomol. Exp. Appl., 
91, 305-316. 
Huang, F., Buschman, L.L., Higgins, R.A. & McGaughey, W. H.  (1999).  Inheritance of resistance to 
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Hunt, T.E., Higley, L.G., Witkowski, J.F., Young, L. J. & Hellmich, R.L.  (2001).  Dispersal of adult 
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Hurley, T.M., Babcock, B.A. & Hellmich, R.L.  (2001).  Bt corn and insect resi stance: An economic 
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Ives, A.R. & Andow, D.A.  (2002).  Evolution of resistance to Bt crops: Directional selection in 
structured environments.  Ecol. Lett., 5, 792-801. 
Jesse, L.C.H. & Obrycki, J.J.  (20 00).  Field deposition of Bt transgenic corn pollen: lethal effects on 
the monarch butterfly.  Oecologia , 125, 241-248. WT/DS291/R/Add.6 
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Jesse, L.C.H. & Obrycki, J.J.  (2004).  Survival of experimental cohorts of monarch larvae following 
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NRC (National Research Council).  (2002).  Environmental effects of transgenic plants: the scope and 
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  Dr. Snow  
1113.  I conclude that yes, new scientific evidence has become available since 1998 with regard to 
gene flow from herbicide-tolerant crops and taking into account the environmental concerns and 
management goals of EC Member States.  New scientific studies published during 1998-2003 showed 
that the dispersal of transgenes that confer resi stance to glufosinate and glyphosate will occur much 
more widely and more quickly than was previously expected, as I discuss in Part I.  Also, new studies 
showed that the widespread use of glufosinate-tolerant and glyphosate-tolerant oilseed rape could lead 
to populations of volunteers and weeds that are mo re difficult to manage than their nontransgenic 
                                                                                                                                                                     
Sears, M.K., Hellmich, R.L., Stanley-Horn, D.E ., Oberhauser, K.S., Pleasants, J.M., Mattila, H.R., 
Siegried B.D. & Dively, G.P.  (2001).  Impact of Bt corn pollen on monarch butterfly populations: a risk 
assessment.  PNAS, 98, 11937-11942. 
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monarch larvae in field studies.  PNAS, 98, 11931-11936. 
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(2001).  Effects of exposure to Event 176 Bacillus thuringiensis corn pollen on monarch and black swallowtail 
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transgenic Bacillus thuringiensis corn tissue in the field. Mol. Ecol. , 12, 765-775.  
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WT/DS292/R/Add.6 
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  predecessors.  Adopting these herbicide-tolerant cr ops could lead to greater dependence on these and 
other herbicides (see Part I and Friesen et al. 2003).   
1114.  These problems would not arise without the use of  transgenic crops b ecause the genes that 
confer resistance to glufosinate and glyphosate have not been found to occur naturally in the crop's 
gene pool.  Although another variety of oilseed rape with resistance to the herbicide imidazolinone is 
widely grown in Canada and Australia, the relativel y minor problems associated with its use could be 
compounded with the addition of transgenes that provide more resistance to more herbicide modes of 
action.  The Canadian regulatory system treats al l herbicide-tolerant crops in a similar manner, 
regardless of whether they are transgenic or not, and it appears that little or no effort has been made to 
avoid gene flow among herbicide- tolerant crops, volunteers, and w eeds. The EC approach differs 
dramatically in that EC considers possible long-term effects that might arise from the combination or successive use of herbicide-tolerant crops. 
1115.  Application rates of glufosinate and glyphosate are expected to increase greatly if these 
herbicide-tolerant crops are adopted by farmers.  In Europe, scientists are still investigating the 
question of whether these types of changes in ag ricultural practices could have unwanted effects on 
farmland biodiversity, relative to ongoing effects of c onventional, nontransgenic crops.  This research 
started during 1998-2003 and findings have recently begun to appear in scientific publications (e.g., 
Watkinson 2000, Firbank 2003, Squire et al. 2003).  Also, in the context of Europe, gene flow 
between transgenic oilseed rape crops and non-transg enic crops is perceived as an economic problem 
due to newly introduced labelling requi rements.  Research is under way to develop effective strategies 
for "coexistence" of transgenic and conventional crops. 
1116.  As discussed above, scientific experts in th e EC have concluded that potential problems 
related to gene flow should be monitored after commercialisation, and that farmers should be educated about appropriate stewardship and manageme nt of herbicide-tolerant crops.  The scientific 
committees of certain Member States (e.g., France) have argued that more research is needed to determine whether problems related to gene flow can be mitigated or avoided after these crops are grown on a large scale.  In Canada and the US, how ever, no measures have been taken to avoid these 
problems.  Glyphosate-tolerant oilseed rape is gr own very widely in western Canada, where this 
herbicide is used in low-till and no-till weed management.   
1117.  Here, I have focused on herbicide-tolerant crops .  Other scientific studies have raised valid 
questions about the persistence of Bt toxins in the environment and their potential to harm nontarget insects (e.g., Losey 1999, Stotzky 2001, Hilbeck 2001).  To my knowledge, these questions largely 
have been resolved by subsequent scientific findings with regard to th e crops that are the focus of this 
dispute. 
1118.  Furthermore, I do not know of any studies or  scientific evidence showing that the process of 
creating transgenic plants is inherently more risky than other methods used in conventional breeding, including mutagensis and embryo rescue following wide crosses. 
1119.  In summary, the types of new scientific informa tion that I discuss in Part I of my answers can 
be used to support the view that potential risks from the products in this dispute could be assessed differently than the risks from biotech products approved prior to 1998. 
Dr. Squire  
1120.  The argument presented in Notes 11-12 is that knowledge of the ecological impacts of biotech 
products and their spread and concentration in the agricultural environment has changed, particularly  WT/DS291/R/Add.6 
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  in that emergent properties at the scales of the field and landscape are now much better appreciated 
even if they are still far from fully underst ood. Examples of where knowledge has increased 
substantively are – 
• Spread and persistence of some crops plants, notably oilseed rape. 
• The important role of insects as carriers of pollen over the landscape. 
• The importance of the weed flora to in-field biodiversity and food webs. 
Question 98:  From a scientific perspective, is there a significant difference in risks to human, 
animal or plant health or the environment ar ising from the use of a bacterial antibiotic 
resistance marker gene, or part thereof, in any biotech product at issue in this dispute (eg, 
Monsanto Bt cotton (531), Monsanto Ro undup Ready cotton (RRC1445), Amylogene starch 
potato) compared to those products of biotec hnology approved by the European Communities 
prior to October 1998?  
Dr. Nutti  
1121.  Answer 98: As I already answered in question 1, it will be necessary a combination of several 
factors for a DNA transfer from plants to microbial  or mammal cells to occur, which is the main 
argument raised in this dispute against the products using antibiotic resistance marker genes. 
1122.  It is important to point out  that according to FAO/WHO (2000), DNA transfer from plants to 
microbial or mammal cells, under normal circumstances of dietary exposure, would require all the following events to occur: 
• the relevant gene(s) would have to be released, probably as a linear fragment; 
• the gene(s) would have to survive nucleases in the plant and in the gastrointestinal 
tract;  
• the gene(s) would have to compete for uptake with dietary DNA; 
• the recipient bacteria or mammalian cells would have to be competent for transformation and the gene(s) would have to survive their restriction enzymes and 
• the gene(s) would have to be inserted in the host DNA by rare repair or recombinant 
events.  
1123.  There have been numerous experiments aimed at evaluating the possibility of transfer of plant 
DNA to microbes and mammalian cells.  To date, there are no reports that marker genes in plant 
DNA transfer to these cells.  Even so, the use of alternative transformation methods, which do 
not use ARMG, is encouraged. If alternative mark er genes are used, they also must be evaluated 
regarding their safety.  
1124.  The transfer of marker genes which confer resistance to kanamycin, ampicillin and 
streptomycin to bacteria in the human gut is unlikely to present a significant health impact since bacteria resistant to these antibioti cs are already spread all over or are naturally found in the human 
gastrointestinal tract (S malla et al., 1993; Calva et al., 1996; Shaw et al., 1993; Smalla et al., 1997). WT/DS291/R/Add.6 
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  Besides, kanamycin/neomycin and streptomycin ar e rarely used for humans due to their collateral 
effects (WHO 1993). 
1125.  My opinion is that, based on the existing lite rature and knowledge on the subject, and from a 
scientific perspective, there is no new evidence that  would suggest that the potential risks to human, 
animal or plant health arising from the use of a b acterial antibiotic resistance marker gene, or part 
thereof, from  any biotech product at issue in this dispute (eg, Monsanto Bt cotton – 531, Monsanto 
Roundup Ready cotton – RRC1445, Amylogene starch potat o) are different in nature or magnitude as 
compared to those products of biotechnology a pproved by the European Communities prior to 
October 1998. 
1126.  I will not comment on any environmental issue, since this is not my area of expertise. 
However, in the areas of food safety, human and an imal nutrition, toxicology and allergenicity, the 
same approach has been used since 1996 to assess the safety of GM products (FAO/WHO Expert 
Consultation, 1996).  The evolution of the safety assessm ent process in the last ten years is very much 
related to the research (which generated a vast bibliography on the subject), discussion and public 
perception/awareness developed during the peri od, when OECD produced several consensus 
documents and the Codex Alimentarius approved the guidelines for the safety assessment of GM 
plants and microorganisms. Also, a lot of resear ch has been conducted in different countries 
(Australia, New Zealand, Japan, USA, European Union etc), in order to improve the whole process. Nowadays, although we have in use (in all steps of the safety assessment) techniques which are more 
refined, the approach remains essentially the same.
135 
Question 99:  For those biotech products at issue in this dispute for which no significantly different nature or level of risk has been id entified, does the information before the Panel 
provide a scientific or technical rationale for monitoring the occurrence of potential adverse 
effects, or of unintentional effects, arising from the consumption or use of these products 
compared to those products of biotechnology ap proved by the European Communities prior to 
October 1998?  
Dr. Nutti  
1127.  Answer 99:  In my opinion, the biotech products at issue in this dispute should be treated in 
the same way as the biotech products approved by the European Commun ities prior to 1998.  
                                                      
135 References:  
FAO/WHO. Safety aspects of genetically modified foods of plant origin. Report of a Joint FAO/WHO 
Expert Consultation on Food Derived from Biotechnology, Geneva, Switzerland, 29 May-2 June 2000. Rome: 
Food and Agriculture Organization of the United Nations. 2000. www.fao.org/es/esn/gm/biotec-e.htm . 
CALVA, J.J.; SIFUENTES-OSBORNIO,  J.; CERON, C. Antimicrobial resistance in fecal flora: 
longitudinal community-based surveillance of children from urban Mexico. Antimicrob. Agents Chemother., vol. 40, pp. 1699-1701, 1996. 
SHAW, K.J., RATHER, P.N., HARE, R.S. AND MILLER, G.H. Molecular genetics of 
aminoglycoside resistances genes and familial relationships of the aminoglycosidemodifying enzymes. Microbiol. Rev., vol. 57, pp. 138-163, 1993. 
SMALLA, K.; VAN OVERBEEK, L.S.; PUKALL, R.; VAN ELSAS, J.D. Prevalence of nptII and Tn5 
in kanamycin resistant bacteria from different environments. FEMS Microbiol. Ecol., vol. 13, pp. 47-58, 1993. 
SMALLA, K.; WELLINGTON, E.; VAN ELSAS, J.D. Natural background of bacterial antibiotic 
resistance genes in the environment. Nordic Seminar on Antibiotic Resistance Mark er Genes and Transgenic 
Plants, p 8-16. June 12-13, 1997, Oslo, Norway. The Norwegian Biotechnology Advisory Board. 
WHO (1993). Health aspects of marker genes in genetically modified plants, Report of a WHO 
Workshop. World Health Organisation, Geneva.   WT/DS291/R/Add.6 
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  1128.  The products approved prior to 1998 are the so called "first generation" products.  Most of 
them had the new trait introduced in order to become insect resistant or herbicide tolerant, and they  
were assessed as equivalent to their conventional counterparts.  The products approved prior to 
October 1998 have been consumed in different regions of the wo rld (USA, Canada, Argentina, 
Australia, New Zealand) and, no adverse effects re lated to their consumption have been reported in 
any of these countries. 
1129.  According to the WHO document "20 Questions on Genetically Modified Foods", available at 
http://www.who.int/foodsafety/publications/biotech/en/20questions_en.pdf , the GM foods currently 
available on the international market have passed risk assessments and are not likely to present risks 
for human health.  In addition, no effects on hu man health have been shown as a result of the 
consumption of such foods by general population in the countries where they have been approved.  
Continuous use of risk assessments based on the Codex principles and, where appropriate, including post market monitoring, should form the basis for evaluating the safety of GM foods. 
Dr. Andow  
1130.  There are some biotech products at issue in th is dispute for which one committee or another 
has determined that were no significant risks.  I have  taken issue with some of these determinations in 
my previous responses.  For all of the products at  issue in this dispute, there are some member 
countries that disagree with the assessment of the relevant SCP (for example) that there are no 
significant identified risks.  This disagreement is  sometimes related to different standards of 
acceptable risk being applied by the disagreeing parties. 
1131.  This disagreement provides the only rationale for monitoring potential adverse effects.  If all 
parties agreed that there were no significant iden tified risks, there would no need to consider 
monitoring for potential adverse effects.   
1132.  Unanticipated effects could arise from a transg ene by any of the following mechanisms:  new 
ORFs, insertional mutagenesis, post-transcriptional or  post-translational processing, other pleiotropy 
or epistasis, and gene-by-environment interaction.  New ORFs and insertional mutagenesis can be addressed through molecular characterization of all transgene loci.  Post-transcriptional or post-
translational processing can be addressed to the most  part by molecular and biochemical analysis.  
Other pleiotropy or epistasis and gene-by-envi ronment interaction cannot be addressed without 
extensive planting in the field. 
1133.  All of these possible sources unanticipated effects are equally likely to occur for plant biotech 
products before 1998 and plant biotech products after 1998.  It is possible that more recent events (after 2001) are less likely to have such unanticip ated effects than those prior to 1998.  The main 
difference between them is that new ORFs, inser tional mutagenesis and pos t-transcriptional and post-
translational processing was not looked for very much before 1998, while after 2001, the methods and 
standards have become increasingly targeted to assess  these possibilities.  This provides a rationale for 
monitoring. 
Dr. Snow  
1134.  This question refers to products for which no si gnificant risks have been identified, whereas 
many of the questions above refer to products fo r which one or more Member States has identified 
potential risks.   WT/DS291/R/Add.6 
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  1135.  With regard to environmental effects, if this question pertains only to products that have no 
identified environmental risks, then there is no sci entific rationale for obligatory monitoring.  One 
could argue that possible risks may have been overlooked prior to marketing, but it is not logical to 
require monitoring for every transgenic crop, regardl ess of its phenotypic traits.  Rather, this might be 
carried out to reassure the public that long-term studies are being conducted, or to ensure that 
labelling thresholds for non-GM products are not exceeded.   
1136.  If gene flow from transgenic crops is viewed as a form of genetic "contamination", then 
determining the extent to which it occurs after deregulation could be seen as a socio-economic reason 
for monitoring.  In this context, scientific knowledge  that was gained after 1998 is relevant because 
many studies showed that gene flow occurs more  widely and more quickly than was previously 
anticipated (see above). 
1137.  In reality, the scientific basis for which envi ronmental consequences to monitor and how to 
do this in a scientifically rigorous manner are not well developed (e.g., NRC 2002).  There are certain 
types of environmental effects for which monitori ng can be justified on scientific or technical 
grounds. Specific and plausible environmental harm s should be identified before allocating time and 
money to these efforts. 
Question 100:  For those biotech products at is sue in this dispute for which an approval has 
been sought for environmental release (notif ications submitted under Directives 90/220 or 
2001/18), and for which no significantly different nature or level of risk has been identified, does the information before the Panel provide a scientifi c or technical rationale for requiring specific 
agricultural management practices that differ from those for products of biotechnology 
approved by the European Communities prior to October 1998? 
Dr. Andow  
1138.  A parallel argument to my response to  question 99 holds for this question. 
Dr. Snow  
1139.  See Answer 99 because the same principles apply. 
Dr. Squire  
1140.  Following the points made in answer to Q.97, the innate biological qualities and behaviour of 
a product may not have changed, but it is quite possi ble that the context in which that product would 
operate has changed, in two ways. (A) The physic al or agronomic environment is different. The 
agronomy of these crops changes rapidly: examples of  factors that have changed markedly in Europe 
in recent times are the proportion of autumn-sown crops, the area covered by oilseed rape, and the 
type and effectiveness of pesticides used. An example, given already, of the change in pesticides is the rise in use of glyphosate as an arable herbicide in  some countries in the past few years. (B) The 
understanding of the GM product's role in the ecosyst em has changed. It was also reported previously 
that some major effects of intensification on arable ecosystems have become well established 
scientifically only in the last few years. The way ar able plants and their food webs are considered is 
now different from the way they were generally considered in the early 1990s. The question is 
sometimes referenced back to before the early 19 90s: why was the large scale change to autumn-sown 
cropping in some parts of Europe not scrutinised w ith the same rigour as the potential change to GM 
cropping? The answer is that it was thought not to be important, while it is now known to have been 
very important for farmland food webs.  WT/DS291/R/Add.6 
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  Question 101:  Does the information before the Pa nel support the argument that any potential 
risks from any of the biotech products at issue in this dispute should be mitigated in a manner 
different than the products of biotechnology approved by the European Communities prior to 
October 1998? If so, what means of risk mitigation might be envisaged? 
Dr. Andow  
1141.  None of the products approved by the EC prior to October 1998 have been mitigated in any 
manner by the EC because no mitigable risks have been reported and verified.  Should any of the 
biotech products cause a verifiable risk, this would be sufficient argument for mitigating them 
differently. 
1142.  However, as indicated in my response to question 97, there are new risk methodologies and 
assessment standards being applied to biotech products today than prior to 1998.  Thus, it is possible 
that risks will be identified for new products that we re not even considered in the older products.  
Under such conditions, differences could be justified. 
Dr. Snow  
1143.  Several of the products that we re approved before 1998 are the same as those in this dispute 
or are very similar.  These include the following,  as listed in the US June 16, 2004 documents: 
Oilseed rape (= Swede rape) 
Glufosinate-tolerant, male sterile (MS1,RF1); C/UK/94/M1/1 
Glufosinate-tolerant (Topas 19/2); C/UK/95/M5/1 
Maize 
Bt-176, glufosinate-tolerant; Ceiba-Geigy; C/F/94/11-03 
Bt cry1A; MON 810; Monsanto; C/F/95/12-02 
Bt-11; glufosinate-tolerant with Bt cry1Ab;  C/UK/96/M4/1 
Glufosinate-tolerant (T25); AgrEvo; C/F/95/12-07 
Chicory 
Glufosinate-tolerant, male sterile; C/NL/94/25 
1144.  The answer to this question hinges on whic h potential environmental risks might require 
mitigation, and whether any new scientific knowledge has become available to justify changes to any mitigation plans that were required prior to October 1998.  
1145.  In summary, I am not sure which mitigation plans may have been required at that time, but 
new scientific knowledge that was gained after 1998 cer tainly could be relevant to risks related to 
gene flow (see above) and the evolution of resist ance in target pests of Bt crops (e.g., NRC 2000). 
1146.  In the case of oilseed rape that was approved for import and processing only, I cannot identify 
new scientific reasons for different mitigation plan s (e.g., using covered vehicles when transporting 
large quantities of seeds). 
Dr. Squire  
1147.  The answers follow from the res ponses above to questions 97 a nd 100. While  products might 
have very similar qualities, mitigation might differ as a result of new information informing risk or a 
new perception of the importance of a particul ar risk. Among ecological topics, the perceived 
mitigation to reduce the 'severity' of a risk to biodiversity and ecosystem functioning has changed WT/DS291/R/Add.6 
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  because of a greater appreciation that arable syst ems have been affected by intense agriculture. 
Mitigation is unlikely to remain constant. For exam ple, some current mitigation measures which leave 
margins round the cropped area of land are insufficient when it is appreciated th at biodiversity in the 
cropped areas is necessary to main ecological function there.  
1148.  That risk has not remained the same over tim e is an inevitable consequence of scientific 
information on arable systems being collected at  increasingly larger scales since the mid-1990s. Early 
research using GMOs in small parcels of land coul d not possibly have generated the knowledge that 
pollen from large fields of oilseed rape is move d widely in the landscape. Moreover, the present 
guidelines about pollen barriers, e.g. a strip of flowering crop between the GM field and non-GM 
recipient field, may have to change if the proportion  of GM fields in the landscape increased to, say, 
50%.  
Comparable novel non-biotech products, (such as plant products produced by selective 
breeding, cross-breeding and induced mutagenesis) 
Question 102:  Does the information before the Pane l support the view that the biotech products 
at issue in this dispute (including products subject to the member State safeguard measures) 
give rise to the same types of potential risks to human, plant or animal health or to the environment as novel non-biotech products, such  as plant products produced by selective 
breeding, cross-breeding and induced mutagenesis?  If so, for any biotech product at issue in 
this dispute are there significant differences, from a scientific perspective, in the nature or 
magnitude of any potential risks from these products compared to comparable novel non-
biotech products taking into account: 
• the specific genetic modification introduced and the resulting product; 
• the intended use of each product (direct human or animal consumption, further 
processing for consumption, planting or other use); 
• any potential risks that may arise from the combination or successive use of biotech products or comparable  novel non-biotech products. 
Please explain with reference to specific products at issue in this dispute. 
Dr. Nutti  
1149.  Answer 102:  It is important to point out that usually the novel non-biotech products, such as 
plant products produced by selective breeding, cross-breeding and induced mutagenesis have not been subjected to any extensive safety assessment as  the plants derived from the Recombinant-DNA 
technology have  been.  I am of the opinion that  both novel non-biotech produc ts and biotech products 
should be assessed in a comprehensive, scientific, step  by step , case by case bases, so the same safety 
assessment principles should be applied in all cases. 
Dr. Andow  
1150.  Comparable non-biotech products from plant bree ding:  Regarding the differences between 
conventional breeding and so-called "molecular breed ing," none of the parties fully represent the 
comparison accurately.  Breeding involves two im portant processes: (1) finding and introducing 
usable genetic variation into the breeding populati on and (2) improving and sel ecting desired varieties 
from the breeding population.  The methods used will depend on the crop, with major differences for  WT/DS291/R/Add.6 
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  clonal species, such as potato and banana versus sexual species, such as oilseed rape, maize and 
soybean.  Among the sexual species, there are ma jor differences in breeding methods between 
outcrossing species, such as maize and oilseed ra pe, and inbreeding species, such as soybean, and 
wheat. 
1151.  Transgenesis is a process to introduce genetic  variation into the breeding population.  
Transgenesis is not a process for finding genetic variation or for selecting and improving varieties.  
Thus, there is no such thing as molecular breeding.  Transgenesis is merely a part of the breeding process. 
1152.  It would seem important then to determine a comparable conventional counterpart to 
transgenesis for introducing genetic variation into the breeding population.  A comparable 
conventional process would be one typically used in br eeding programs rather than one rarely used.  If 
possible a comparable conventional process would introduce genetic variation during a similar or 
analogous step in the breeding process.  The breed ing process can eliminate considerable genetic 
variation, so variation introduced very early in  the breeding process, will be screened and selected 
multiple times by multiple breeding programs prior to use, while va riation introduced much later in 
the process will receive fewer screenings  and possibly no additional selection. 
1153.  Several other methods exist to introduce genetic  variation into the breeding population.  
These include wide crossing, crossing or using una dapted material, mutagenesis, and recombining 
diverse adapted material.  Wide crossing involves cr osses with different species.  Unadapted material 
are plants of the same species (or subspecies) th at have not previously been used in breeding 
programs.  Adapted materials are those that have already been used to produce modern conventional 
varieties.  There is a range of "adaptedness" ev en within these materials, with some breeding 
programs relying primarily on the most recently us ed popular varieties and other programs reaching 
further back in time for older varieties as the source of genetic variation.   
1154.  Crossing methods are difficult to use routin ely for clonal and inbreeding species.  For 
example, in potato, genetic varia tion is conventionally introduced by growing plants to flowering and 
crossing material, or via deliberate or spontaneous mutation during cell culture.  The crossing methods take a longer time to produce usable variet ies.  For example some characters have not been 
incorporated in usable varieties despite over 30 y ears of work.  Cell culture is essential for producing 
new potato seed stock, so it is a routine way to introduce genetic variation and transgenesis introduces 
genetic variation in cell culture.  Thus for transgenic potatoes, the most relevant conventional 
comparison is deliberate or spontaneous mutation in cell culture. 
1155.  For inbreeding species, such as soybean and dry bean, variation can be introduced by hand 
pollinations (usually involving ad apted material), or by using new collections because inbreeding 
lines will breed true to type.  In some cases it is possible to create situations where the inbreeding plant will outcross at higher rates.  In this way, it is possible to introduce variation using crossing 
methods.  However, because the crossing methods typically are difficult, most programs do not use 
them very much.  All programs rely on evaluating co llections (sometimes an old collection in a new 
environment) for new, usable genetic material.  For these species, transgenesis is a new and powerful 
method for introducing genetic variation directly into the adapted modern varieties, thereby avoiding the expense of crossing and the arbitrariness of collections.  Thus, it is not clear that there is a 
comparable conventional method.  
1156.  For outcrossing species, such as maize and oil seed rape, there are many means to introduce 
genetic variation.  For modern maize breeding, however, wide crosses and crossing with unadapted 
materials are not used in the vast majority of br eeding programs in the world.  Many public sector WT/DS291/R/Add.6 
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  programs devote some resources to these, but they are viewed as long term breeding efforts that may 
produce improved populations over decadal periods.  These improved populations may or may not be picked up by other breeding programs for introducti on into their unimproved breeding populations.  
By far the most common method for introducing new genetic variation into a maize population for breeding is recombination of adapted material.  However, dwarfing even this method is "backcrossing," which is a method for introducing a specific genetic trait into an adapted inbred line.  Both conventional and transgenic traits are introdu ced into adapted inbred lines via backcrossing.  
However, for maize, recombination of adapted mate rial is probably the most relevant conventional 
comparison to transgenesis.  
Types of risks : 
1157.  As found by all scientific panels addressing this issue, there are no differences in the types or 
kinds of risks posed by biotech crops compared wi th their non-biotech counterparts.  The kinds of 
risks include toxicity to humans and animals, allerg enicity, nutrition, potential for producing disease, 
gene flow risks, non-target and biodiversity risks, and resistance risks.   
Nature or magnitude of risks : 
1158.  Within these kinds of risk, there are new risks of biotech plants. 
1159.  The EC is correct in pointing out that both biolistic and Agrobacterium-mediated 
transformation typically results in multiple transgene loci, typically with complex structure.136  Unlike 
bacterial transformation, where what is intended to be inserted typically is inserted just as intended, 
this is not typical using the present plant transformation methods.  One of the main concerns arising 
from this are new open reading frames (ORFs).  An ORF is a DNA sequence that could theoretically produce a protein.  A new ORF could theoretically produce a new protein, which could cause or influence a new risk. 
1160.  The EC and the US is correct to identify in sertional mutagenesis as another outcome of 
transgenesis that is new to breeding, and could cause or influence a new risk. 
1161.  Canada is incorrect to claim that transgenesis allows more precise control than selective 
breeding.  First both transgenic and conventional varieties undergo some level of selective breeding, so the comparison is inappropriate.  More importa ntly, transgenesis allows control over the intended 
result (and in this sense, there is no dispute that transgenesis allows more precise control), but the 
actual result is often different. 
1162.  The US, Canada and Argentina are correct to say that translocations and other genomic 
disruptions can occur in conventional breeding.  However, these genomic disruptions are normally 
rare in conventional breeding.  Moreover, their frequency of occurrence is much higher when genetic variation is introduced using wide crossing than th e more typically used recombination of adapted 
materials.   
1163.  Thus, the magnitude of ORFs and insertional mutagenesis introduced by transgenesis is 
higher than that introduced by recombination of ad apted materials.  It also may be higher than 
deliberate or spontaneous mutation in cell culture, although this is less certain. 
                                                      
136 Please refer to additional detail in my response to question 9.  WT/DS291/R/Add.6 
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  1164.  There is considerable research being conducted to understand and control the transgene 
insertion process, and it is likely that over the ne xt decade technical improvements will alter these 
concerns. 
1165.  Some of the ORFs and extraneous transgene loci can be eliminated by independent 
assortment for outbreeding plants, such as maize.  This is less possible for inbreeding plants and 
clonal plants. 
1166.  Nearly all risks associated with novel toxins (e.g ., all Bt crops) introduced into crop plants are 
new risks.  While there are comparable risk asse ssment models for assessing these risks (toxins in 
plants), and the risks of the particular toxins may have been investigated outside the plant, the fact that 
the plant is used as the delivery vector for the t oxin and the precise expression patterns in the plant 
mean that new species are exposed in new ways.  These are new risks. 
1167.  Other risks of a new nature have been iden tified in some of my responses to the other 
questions. 
1168.  The intended use of the product does not affect the nature of the risk, but it does affect the 
rusk quantitatively.  This is an effect of scale.   For example, risks associated with releases for 
processing are smaller than the same risks for the sa me product for planting and other use.  It is not 
clear how much smaller, but in some cases (biodive rsity risks of GMHT crops), it could be nil for 
processing uses while it at the same time is was substantial for cultivation uses. 
1169.  Risks may change quantitatively from the comb ination of transgenes, because it will not be 
possible to maintain seed supplies of all possible combinations of traits.  Suppose a crop, such as 
cotton, was available mainly with both a GMHT gene and at Bt gene.  Suppose the insect pest is a sporadic one on cotton, but a major one on maize.  Farmers would have less incentive to use the Bt 
gene, but may have a strong desire to use the GMHT gene.  This would lead to an over use of the Bt 
gene in cotton, increasing resistance  risk both in cotton and maize. 
Dr. Snow  
1170.  In my opinion, and only in reference to environmental risks, the biotech products in this 
dispute could be considered as different from non- biotech products in the some cases, such as: 
• Pesticide-producing crop plants –  
– Non-biotech maize does not produce proteins that are toxic to insects, 
including pollen that can kill lepidop terans (butterfly and moth lavae), 
whereas Bt maize does (especially  Bt-176, see NRC 2002).  Here, one 
concern is that drifting maize polle n could land on the food plants of 
susceptible, non-target insects and kill them .  Although this risk has largely 
been discounted as the result of several i nvestigations in the USA, it is still a 
question that scientific advisory panels must consider for all Bt crops.  Other 
non-target effects of Bt maize also require evaluation, including possible 
unwanted effects on soil invertebrates, pollinators, ladybird beetles, and other 
beneficial insects. 
 
• Herbicide-tolerant crop plants with feral ( volunteer) populations or wild relatives that 
can hybridise with the crop: 
– See answers to Question 6 and others.  Glyphosate-resistance has not been 
introduced into crops using non-trangenic methods, so this particular trait is WT/DS291/R/Add.6 
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  linked to novel transgenic products .  Because glyphosate is used so 
extensively, weedy Brassica rapa populations that acquire the transgene for 
glyphosate resistance might become more common in and around farmers' 
fields.  In the future, this process could occur many types of crops/weed 
systems where weedy relatives of crops (e.g., weedy rice, chicory, carrot, 
sunflower, sorghum, sugar beet, turf grass, etc.) are controlled using glyphosate.  Also, the herbicide glyp hosate provides certain environmental 
benefits (such as facilitating no-till ag riculture and replacing more toxic 
herbicides) that could be lost if there is extensive gene flow to volunteers and 
wild relatives, and if over-use of the herbicide selects for other glyphosate-resistant weeds.  These problems are possible with all types of herbicide-
tolerant crops, unique features of glyphosate make it a special case.   
 
Question 103:  Does the information before the Pane l support the view that any of the biotech 
products at issue in this dispute poses a substa ntially greater risk as regards the direct or 
indirect consequences of unintentional "contamination" of other plant varieties than a 
comparable novel non-biotech products, such as one of the 2300 different crop varieties that have been developed using induced mutagenesis?
137  If so, what means of risk mitigation might 
be envisaged?  
Dr. Nutti  
1171.  Answer 103:  My understanding is that plants that were developed us ing induced mutagenesis 
should be subjected to the same risk assessment used for plants produced  from the Recombinant-DNA 
technology.  In my opinion, crop varieties that have been developed using induced mutagenesis can 
pose the same risk to human or animal health and, up to now, they have not been properly assessed. I 
believe that guidelines should be developed for th e safety assessment of these plants, and that the 
FAO/WHO Codex Guideline for the Conduct of F ood Safety Assessment of Foods Derived from 
Recombinant-DNA Plants could be used as baseline. 
Dr. Andow  
Risk and "contamination":    
1172.  This will depend on the scale of release and the nature of the adverse effect. 
1173.  Risk is a combination of exposure and an adverse effect.  Exposure will be determined by the 
properties of the crop plant and the quantity of each planted (scale of release).  There is little evidence 
to suggest that ceteris parabis, gene flow will be greater from a transgenic variety than a conventional 
one.138   
1174.  The definition of an adverse effect entails speci fication of who or what will be affected and 
how is this effect considered adverse.  Thus an organic farmer may find contamination adverse because it removes his or her product from the organic food stream.  This could be considered adverse 
because of economic loss and lose of quality of life or livelihood.   
                                                      
137 FAO/IAEA (Food and Agriculture Organization of the United Nations/International Atomic Energy 
Agency). 2001. FAO/IAEA Mutant Varieties Database.  Available online at http ://www-infocris.iaea.org/MVD/. 
138 Some transgenic plants may have lower levels of gene flow, such as the male-sterile oilseed rape 
varieties.  WT/DS291/R/Add.6 
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  1175.  There has been little discussion and less agreement over the nature of the adverse effects of 
contamination.  For example, there can be ec onomic and livelihood harms associated with the 
perception of adverse effects.  It is not clear to  me that there is agreement that these kinds of 
perceived risks should be considered. 
1176.  For the example in paragraph 1174 , the risk associated with biotech crops is substantially 
greater than the risk asso ciated with any of the conventionally pr oduced varieties.  However, this is 
largely due to the definition of the harm. 
1177.  Although there is little data to support this hypoth esis, I would suggest that the probability of 
cross-contamination rises slowly with spatial scale for very small scale production, but once it reaches 
a large-size threshold, the probability rises much fast er.  In general, "contamination" will be a spread 
process for which there is no advantage of the transg ene in the invaded/ contaminated habitat, but 
there is an advantage in the habitat of origin.  In these cases, spread scales with the length of the 
boundary between the two habitats (not the area of  either) and linearly with the square of time.139  
However, at very small spatial scales, it is likely th at managers will be able to take greater care in 
limiting accidents, resulting in lower contamination rates. 
Dr. Snow  
1178.  The question of whether any of the biotech pr oducts in this dispute poses a substantially 
greater risk due to "contamination" than non-biot ech products depends on what types of risks each 
party is trying to avoid (see Part I).   If one considers that standard th resholds have been established to 
allow the "coexistence" of biotech and non-biotech crops in Europe, then by definition contamination 
is an issue for all biotech products.  Very low le vels of contamination can  be detected using DNA 
markers, with the result that contamination, also  known as "adventitious presence," has been detected 
routinely in non-biotech products.  Labeling a nd traceability have not been required for novel non-
biotech products such as those that were develope d using mutagenesis, nor would any high-resolution 
identifying markers be availa ble for these types of crops. 
1179.  Another way to answer this question is to focu s on the characteristics of biotech crops – their 
phenotypes – rather than the mere pr esence of transgenes.  This is more appropriate if the goal is to 
avoid direct or indirect harms to human, plant or animal health, or the environment.  The present 
dispute involves only a few crop species with a limite d number of transgenic traits, and the question is 
whether the dispersal of these traits to other plants, by means of pollen and seed movements, could 
pose substantially greater risks as compared to non-GM  traits.  See Part I and answers to Question 6 
and others above for examples of risks that are gr eater in certain GM crops as compared to their non-
GM predecessors. 
Dr. Squire  
1180.  A certain level of impurity – through one cr op type growing within or giving pollen to 
another type – seems to have been generally accepted for many years. Such impurity varies greatly 
with crop type: it is common in oilseed rape, and l ess common in beet and maize, for example. Where 
the nature of the yield is different, e.g. for high  erucic oilseed rape (HEAR), impurities are kept to 
acceptably low values by using registered growers who are familiar with the crop and with the requirements for separation, and many of whom farm in a restricted part of the country. There are clear criteria for the acceptable presence of HEAR in non-HEAR oil. Outside specialist varieties such 
                                                      
139 This is much slower than for species invasions, which scale on the square root of the area occupied 
and linearly with time. WT/DS291/R/Add.6 
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  as HEAR, impurities have largely gone unobserved,  and in many instances where non-GM oilseed 
rape volunteers emerge in a non-GM oilseed rape crop, the percentage impurity is unknown and is 
ignored. The potential of a crop variety to convey an impurity is not the same for all varieties but 
differs depending on factors such as the proportion of  seeds that enter dormancy, the persistence of 
seeds in the soil and the relative pollen 'strength' of  potential donor and recipient fields (for example 
caused by different proportions of male sterile pl ants). These factors may or may not differ between 
GM and non-GM varieties but should not differ be cause one is GM and the other not. They would 
differ in any case. Given present knowledge of the life  cycle and reproductive behaviour of  the crops, 
there is no reason to suppose that biotech crops confer different degrees of impurity compared with 
crops produced from, say, induced mutagenesis.  
Question 104:  From a scientific perspective, is there a significant difference in risks to human, animal or plant health or the environment ar ising from the use of a bacterial antibiotic 
resistance marker gene, or part thereof, in any biotech product at issue in this dispute (eg, 
Monsanto Bt cotton (531), Monsanto Ro undup Ready cotton (RRC1445), Amylogene starch 
potato) compared to novel non-biotech products, such as comparable plant products produced 
by selective breeding, cross-breeding and induced mutagenesis?  
Dr. Nutti  
1181.  Answer 104: As I pointed out before, the use of  antibiotic resistant marker genes has been 
recognized as a safe tool and its employment should be evaluated on a case by case basis.  The same 
rule should be applied to novel non-biotech produc ts, such as comparable plant products produced by 
selective breeding, cross-breeding and induced mu tagenesis.  I mean, these products should be 
evaluated on a case by case basis, so the same safety assessment principles should be applied in all 
cases. 
Question 105:  For those biotech products at issue in this dispute for which no significantly different nature or level of risk has been identified, is there a scientific or technical rationale for 
monitoring the occurrence of pote ntial adverse effects, or of unintentional effects, arising from 
the consumption or use of these products compared  to novel non-biotech products, such as plant 
products produced by selective breeding, cross-b reeding and induced mutagenesis? If so, would 
such monitoring relate to the specific genes or tr aits introduced into a biotech product, and how 
would this compare with the monitoring of induced changes in novel non-biotech products? 
Dr. Nutti  
1182.  Answer 105:  I am of the opinion that the monitoring of occurrence of potential adverse 
effects or of unintended effects should be carried out  based on scientific parameters in both cases, that 
is, for those biotech products at issue in this dispute, for which no significantly different nature or level of risk has been identified, and for novel non- biotech products, such as plant products produced 
by selective breeding, cross-breeding and induced mutagenesis.  In both cases, I am considering that the products were assessed as safe.   
1183.  It is important to point out that usually the novel non-biotech products, such as plant products 
produced by selective breeding, cross-breeding and i nduced mutagenesis have not been subjected to 
any extensive safety assessment as the plants derived from the Recombinant-DNA technology have been. 
1184.  I also think that the methodologies which will be used for this monitoring need to be 
evaluated very carefully since it will be very difficult  to monitor any effect that we are not aware of.  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
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  Therefore, I think this is one good point to be in troduced in the agenda of the Codex Alimentarius 
Task Force on Foods Derived from Biotechnology,  which will start working in September 2005. 
Dr. Andow  
Rationale for monitoring:    
1185.  There are some biotech products at issue in th is dispute for which one committee or another 
has determined that were no significant risks.  I have  taken issue with some of these determinations in 
my previous responses.  For all of the products at  issue in this dispute, there are some member 
countries that disagree with the assessment of the relevant SCP (for example) that there are no 
significant identified risks.  This disagreement is  sometimes related to different standards of 
acceptable risk being applied by the disagreeing parties. 
1186.  This disagreement provides the only rationale for monitoring potential adverse effects.  If all 
parties agreed that there were no significant iden tified risks, there would no need to consider 
monitoring for potential adverse effects.   
1187.  Unanticipated effects could arise from a transg ene by any of the following mechanisms:  new 
ORFs, insertional mutagenesis, post-transcriptional or  post-translational processing, other pleiotropy 
or epistasis, and gene-by-environment interaction.  New ORFs and insertional mutagenesis can be 
addressed through molecular characterization of all transgene loci.  Post-transcriptional or post-
translational processing can be addressed to the most  part by molecular and biochemical analysis.  
Other pleiotropy or epistasis and gene-by-envi ronment interaction cannot be addressed without 
extensive planting in the field. 
1188.  Under present technologies, transgenes can generate new ORFs and insertional mutagenesis.  
Post-transcriptional and post-translational processing may relate to the structure of the transgene and 
the nature of the gene product.  Products novel to the plant probably require closer assessment.  A gene product native to the recipient plant may be less subject to processing, except if it is expressed in 
new tissues.  Novel products probably require cl oser assessment than native products for other 
pleiotropy or epistasis and gene-by-environment interaction. 
1189.  Monitoring can be used to look for unanticipated effects. 
1190.  A less thorough molecular and biochemical ch aracterization of the transgene locus and 
transgene products provides increased pot ential for unanticipated effects.   
1191.  Monitoring may be partially substitutable for molecular and biochemical characterization. 
1192.  Monitoring may also substitute for identifying all possible effects, by covering various 
categories of unanticipated effects.  If a thor ough molecular analysis is conducted, it would seem 
important to ensure that monitoring for the remaining unanticipated effects is not too expensive. 
Comparison with non-biotech varieties:   
1193.  For monitoring related to a specific potential adver se effect, this would have to relate to the 
specific genes/ traits in the transgenic crop.  For monitoring for unanticipated effects, a more general approach is needed. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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  1194.  First, I should make clear that some conventiona l non-transgenic plants have risks, some of 
which may justify monitoring (and management). 
1195.  For potential adverse effects, the reasoning I have  used here implies that the potential adverse 
effect is not a potential adverse effect from a conventional non-transg enic plant.  Otherwise there 
would be no disagreement as I have posited in paragraph 1185 . 
1196.  For unanticipated effects, there is a quantitative difference in some of the concerns related to 
the process of transgenesis (paragraph 1162 ), and differences related to the novelty of the transgene 
product (paragraph 1188 ).  Native biotech products may or ma y not be different from conventional 
breeding for unanticipated effects stemming from other pleiotropy or epistasis and gene-by-
environment interaction. 
Dr. Snow  
1197.  My conclusion is that it does not seem logical to require monitoring if no risk has been 
identified (see Question 99).  Also, both transgenic  methods and other methods used crop breeding 
can result in unintended effects, and in my opini on there is no basis to assume that these unintended 
effects would be substantially greater in transgenic plants.   
Question 106:  For those biotech products at is sue in this dispute for which an approval has 
been sought for environmental release (notif ications submitted under Directives 90/220 or 
2001/18), and for which no significantly different nature or level of risk has been identified, does the information before the Panel provide any sci entific or technical rationale for requiring 
specific agricultural management practices that differ from those for novel non-biotech products, such as plant products produced by selective breeding, cro ss-breeding and induced 
mutagenesis? 
Dr. Andow  
Rationale for management:   
1198.  There are some biotech products at issue in th is dispute for which one committee or another 
has determined that were no significant risks.  I have  taken issue with some of these determinations in 
my previous responses.  For all of the products at  issue in this dispute, there are some member 
countries that disagree with the assessment of the relevant SCP (for example) that there are no 
significant identified risks.  This disagreement is  sometimes related to different standards of 
acceptable risk being applied by the disagreeing parties. 
1199.  This disagreement provides the only rationale for risk management.  If all parties agreed that 
there were no significant identified risks, there wo uld no need to consider monitoring for potential 
adverse effects.  If only some of the parties recognized the risk, then some kind of conditional risk management could be justified.  For example, one condition for the management measures could be 
the country of use. 
Dr. Squire  
1200.  Provided no significant level or type of risk has been detected, then no particular change in 
practice above the highest recommended existing prac tice to ensure a high purity, should be needed. 
As in Q.103, however, if thresholds are imposed fo r whatever reason, e.g. 0.9%, specifically for GM 
varieties in non-GM varieties, then there will need to be different agricultural practices for those GM  WT/DS291/R/Add.6 
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  varieties that leave volunteers or spread genes by pollen to neighbouring, sexually compatible crops. 
These practices are well appreciated – reducing volunteers to a minimum by appropriate soil 
cultivation after harvest, preventing volunteers from flowering in subsequent crops, leaving several 
years before growing the same type of crops again so that volunteer seed decays by natural means, 
leaving a separation strip between crops which is  not harvested and beyond which geneflow is 
reduced to very low values, and not planting crops having reduced self-pollen in the vicinity.  
1201.  Under a system of coexistence in which a threshold (GM in non-GM) was imposed, the 
agricultural practice might well have to change in a crop such as oilseed rape to ensure that threshold would be met.  Longer intervals than normal betwee n oilseed rape crops, some regional segregation of 
GM and non-GM crop types and the dropping of vari etal associations (80% male sterile, 20% own 
pollen) from general use would probably be necessary. Given present knowledge, these changes 
would be in consequence of an imposed threshol d of GM in non-GM product, not of any inherent 
food-risk in the GM product itself. 
Foods produced with biotech processing aids140, including yeasts, bacteria or enzymes that have 
been modified using recombinant DNA technology 
Question 107:  Does the information before the Pane l support the view that the biotech products 
at issue in this dispute (including products subject to the member State safeguard measures) 
give rise to the same types of potential risks to human, plant or animal health or to the 
environment as foods produced using biotech processing aids, including yeasts, bacteria or 
enzymes that have been modified using recombin ant DNA technology?   If so, for any biotech 
product at issue in this dispute are there signif icant differences, from a scientific perspective, in 
the nature or magnitude of any potential risks from the products at issue in this dispute 
compared to foods produced with biotech proces sing aids, taking into account the intended use 
of each product (direct human or animal cons umption, further processing for consumption, 
release into the environment, any other use). 
Dr. Nutti  
1202.  Answer 107: According to the information before  the Panel, and the existing bibliography in 
this field, my view is that the safety of the biotech products at issue in this dispute (including products 
subject to the member State safeguard measur es) should be assessed according to the FAO/WHO 
Codex Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-
DNA Plants, in order to evaluate the potential risks to human, plant or animal health.  
1203.  For foods produced using biotech processing aids , including yeasts, bacteria or enzymes that 
have been modified using recombinant DNA technology, it is important to point out that the microorganisms which produces the processing aid was modified and NOT the processing aid itself. Therefore, I am of the opinion that the safety of the new microorganisms and of the product thereof 
should be assessed according to the FAO/WHO Codex Guideline for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA Microorganisms. 
                                                      
140 "Processing aid" is defined by the Codex Alimentarius  as "any substance or material, not including 
apparatus or utensils, and not consumed as a food ingredient by itself, intentionally used in the processing of 
raw materials, foods or its ingredients, to fulfil a cer tain technological purpose during treatment or processing 
and which may result in the non-intentional but unavoidable presence of residues or derivatives in the final 
product". WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-252 
  
  1204.  It is important to recognize that in both cas es the safety assessment should be carried out in 
order to evaluate the existence of any potential risks. If the intended use of the two different 
categories of products (foods and processing aids) is taken into account, the first point to be 
considered is that processing aids are used in ve ry small amounts in food products, so the direct 
human or animal consumption of processing aids obtained through the recombinant DNA-technology will be much lower than foods derived from Recombinant-DNA plants.  As far as further processing for consumption is concerned, most of the foods  that are consumed nowadays is subjected to 
processing, so this point cannot be considered as a difference among the two product categories. 
Dr. Andow  
Kinds of risk:    
1205.  In general, foods produced with biotech processing aids are not expected to be able to self-
reproduce in the environment.  Thus the kinds of risk associated with these foods do no include any of 
the environmental risks associated with transgenic plants.   
1206.  Foods produced with biotech processing aids can ha ve some non-target effects if the food is 
available in the environment.  These effects are more  similar to the effects of chemicals rather than 
the effects of living biological organisms. 
Nature and magnitude of risk:   
1207.  I will not address human or animal health hazards.  The following comment, however, has 
some implications for human and animal health hazards. 
1208.  As I have argued in question 9 and 102, in tran sgenic plants, unanticipated effects could arise 
from a transgene by any of the following mechan isms:  new ORFs, insertional mutagenesis, post-
transcriptional or post-translational processing, other pleiotropy or epistasis, and gene-by-environment 
interaction.  For each of the potential sources of una nticipated effects, the likelihood of it occurring in 
a transgenic bacterium or yeast (that is typically u sed as a food processing aids) is much lower than in 
a transgenic plant.  For transgenic bacteria and fungi (especially yeast), transgene insertion is more 
predictable and the probability of new ORFs is much lower.  Transgenic bacteria and yeast are much 
easier to screen and eliminate insertional mutations.  Moreover, there is considerably less post-transcriptional and post-translational processing of gene products in bacteria and yeast than in plants.  
Finally the genome size is smaller in bacteria and y east and they are used in a much more restricted 
set of environments than plants, so risks associated  with other pleiotropy and epistasis and gene by 
environment interaction are less. 
Question 108:  Is there a significant difference in risks to human, animal or plant health or the environment arising from the use of a bacteri al antibiotic resistance marker gene, or part 
thereof, in any biotech product at issue in this dispute (eg, Monsanto Bt cotton (531), Monsanto Roundup Ready cotton (RRC1445), Amylogene starch  potato) compared to foods produced 
with biotech processing aids, including yeasts, bacteria or enzymes that have been modified using recombinant DNA technology?  
Dr. Nutti  
1209.  Answer 108:  As I pointed out before, the use of antibiotic resistance marker genes has been 
recognized as a tool that can be safely used, and that its use should be evaluated on a case by case 
basis.  The same applies to processing aids, that  is, the processing aids derived from Recombinant- WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-253 
 
 
  DNA microorganisms should be evaluated on a case by case basis.  Therefore, the same safety 
assessment principle should be applied in both cases. 
Question 109:  For those biotech products at issue in this dispute for which no significantly 
different nature or level of risk has been id entified, does the information before the Panel 
provide a scientific or technical rationale for monitoring the occurrence of potential adverse 
effects, or of unintentional effects, arising from the consumption or use of these products 
compared to foods produced with biotech processing aids?  Does the information before the Panel provide a scientific or technical rationale for mitigating any potential risks arising from 
the biotech products at issue in this dispute in a manner differently than products produced 
with biotech processing aids? 
Dr. Nutti  
1210.  Answer 109:  For those biotech products at issue in this dispute for which no significantly 
different nature or level of risk has been iden tified and for foods produced with biotech processing 
aids, where the processing aid and the Recombinant-DNA microorganism have been assessed as safe, 
I am of the opinion that the monitoring of occu rrence of potential adverse effects or of unintended 
effects, in both cases, should be conduc ted based on scientific parameters.  
1211.  I also think that the methodologies which will be used for this monitoring need to be 
evaluated very carefully since it will be very difficult  to monitor any effect that we are not aware of.  
Therefore, I think this is one good point to be in troduced in the agenda of the Codex Alimentarius 
Task Force on Foods Derived from Biotechnology,  which will start working in September 2005. 
Dr. Andow  
Monitoring and Mitigation:    
1212.  There are some biotech products at issue in th is dispute for which one committee or another 
has determined that were no significant risks.  I have  taken issue with some of these determinations in 
my previous responses.  For all of the products at  issue in this dispute, there are some member 
countries that disagree with the assessment of the relevant SCP (for example) that there are no 
significant identified risks.  This disagreement is  sometimes related to different standards of 
acceptable risk being applied by the disagreeing parties. 
1213.  This disagreement provides the only rationale fo r monitoring or mitigating potential adverse 
effects.  If all parties agreed that there were no significant identified risks, there would no need to 
consider monitoring for potential adverse effects.   
1214.  Unanticipated effects could arise from a transg ene by any of the following mechanisms:  new 
ORFs, insertional mutagenesis, post-transcriptional or  post-translational processing, other pleiotropy 
or epistasis, and gene-by-environment interaction.  New ORFs and insertional mutagenesis can be addressed through molecular characterization of all transgene loci.  Post-transcriptional or post-
translational processing can be addressed to the most  part by molecular and biochemical analysis.  
Other pleiotropy or epistasis and gene-by-envi ronment interaction cannot be addressed without 
extensive planting in the field. 
1215.  All of these possible sources unanticipated effect s are more likely to occur for plant biotech 
products than for foods produced with biotech processing aids.  This provides a rationale for monitoring, but no rationale for mitigation, as ther e are no concrete effects that can be mitigated. WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-254 
  
  Question 110:  On the basis of the information be fore the Panel, is there any scientific evidence 
to support the hypothesis that animal feed made from biotechnology plants alters the 
composition of the food derived from animals consuming the feed?    
(a) If so, what is the likelihood that this event could lead to adverse effects on 
human or animal health?  (see, inter alia , exhibit US-144)  
(b) What risk management options are available to mitigate any resulting risks and what is their efficacy? 
Dr. Nutti  
1216.  Answer 110:  I am not aware of any scientific  evidence that supports the hypothesis that 
animal feed made from biotechnology plants alters the composition of the food derived from animals 
consuming the feed.  One of the studies provided at US-144 showed no difference in milk produced from lactating cows fed rations with genetically modified whole cottonseed to milk produced from 
cows fed non genetically modified but genetically similar cottonseed. The study showed that no milk 
samples were positive for tr ansgenic or plant DNA fragments at the limits of detection for the assays 
following detailed data evaluation criteria.  The DMI,  milk yield, milk composition, body weight and 
body composition score did not differ among treatment s.  The study showed that cottonseed from 
genetically modified varieties used in these studi es yielded similar performance in lactating dairy 
cows when compared to non transgenic control and reference cottonseed.  
1217.  The second study used dehulled soybean meal prepared from genetically modified, herbicide 
tolerant soybeans and near isogenic conventional soybeans in an experiment with growing-finishing pigs.  The study concluded that rate  and efficien cy in weight gain, scanned backfat ,longissimus area  
and calculated carcass lean percentage were not diffe rent for pigs fed diets containing conventional or 
Gm soybean meal. Composition of the meat and sens ory scores were not influenced by diet.  The 
results indicated that Roundup Ready soybean meal is essentially equivalent in composition and 
nutritional value to conventional soybea n meal  for growing-finishing pigs. 
1218.  These are not the only studies that had been ca rried out for the comparison of composition of 
the food derived from animals consuming GM grains, pl ants or meals.  Dr. Marjorie Faust, from Iowa 
University has conducted this type of studies since 1997, with different crops and different animals, 
and up to now, the results showed no difference in the composition of the products or in the animal 
performance.141 
                                                      
141 References:  
Faust, M., and L. Miller.1997 Study finds no Bt in milk. ISU International Crop Management 
Nwesletter ICC-478. Fall Special Livestock Edition. pp  6-7. Iowa State University Extension, Ames. 
Faust, M., and S.M. Spangler. 2000. Nutritive valu e of silages from MON810Bt and non- Bt near 
isogenic corn hybrids. J. Dairy. Sci.83:1184. 
Hammond  et al.1996 The feeding value of soybeans fe d to rats, chickens, catfish and dairy cattle is not 
altered by genetic incorporation of glyfosate tolerance. J.Nutr.126:717-727. 
Padgett at all 1995. Development, identification and characterization of a glyphosate –tolerant soybean 
line. Crop Sci.35:1451-1461. 
ILSI ( 2004)  "Nutritional and Safety Assessments of Foods and Feeds Nutritionally Improved through 
Biotechnology". Comprehensive Reviews in Food Science and Food Safety at 
http://www.ift.org/pdfs/crfsfs/crfsfsv3n2p0035-0104ms20040106.pdf .  WT/DS291/R/Add.6 
 WT/DS292/R/Add.6 
 WT/DS293/R/Add.6 
 Page H-255 
 
 
  Question 111:  Please provide an assessment of th e US statements regarding the evaluation of 
the safety of biotech products in paragra phs 128-133 of the US Supplementary Rebuttal 
Submission, and in particular of the statement in the last sentence of paragraph 133 that: 
"...where all of the data consistently provide no indication of adverse effects, and there is no 
specific indication that the data submitted are in adequate, there is generally no reason to expect 
that any remaining risk as gone undetected, and that further studies are warranted".  What relevance does the foreseen end product use(s) have in  the context of the evaluation of the safety 
of that product?   
Dr. Nutti  
1219.  Answer 111:  As I had pointed  out in several answers, and based on the Codex Alimentarius 
Guidelines for the Conduct of Food Safety Asse ssment of Foods Derived from Recombinant-DNA 
Plants (CAC/GL 45-2003), paragraphs 34 to 43, A ssessment of Possible Toxicity, we have at 
paragraph 37 that the use of a ppropriate conventional toxicol ogy or other studies on the new 
substance may be necessary if, taking into account its function and exposure,  doubts about the safety of the new substance remain.  My understanding is that  if the toxicological assessment has  
presented safety studies on protein digestion in mammalian gastric and intestinal systems, acute 
gavage studies in mice, homology to known toxins and allergens, and exposure to human diet that has no indication of adverse effects, and  the comparison of the GM and its conventional 
counterpart has been properly conducted and showed equivalence,  there is generally no reason 
to expect any remaining risk.  
1220.  The relevance of the end product use(s) is consid ered in the safety assessment, if we consider 
that we have the comparison not only between the GM grain or plant and its conventional counterpart, 
but we also have to compare the composition of prod ucts thereof, for instance in the case of soybeans 
the comparison has considered different processed pr oducts as:  soy meal, defatted soy meal, toasted 
flour, non toasted flour, refined oil, isolated protein and extruded soy protein. 
Dr. Snow  
1221.  In general, the scientific arguments in para graphs 128-133 are valid, but the US does not 
acknowledge possible inherent shortc omings of small-scale, short-duration field tests.  The US 
correctly states that: "Such tests are designed prim arily to examine whether the bioengineered plant 
exhibits the intended characteristics."  However, the se tests rarely address environmental risks such as 
the potential consequences of interbreeding with wild or weedy relatives, as the US claims.  In 
paragraph 131, the US states that "effects on ot her organisms in the ecosystem" are evaluated, 
including "indirect impacts, such as those on fa rming production methods".  However, the methods 
for making these evaluations are not explained or cited.   
1222.  Here, I think it is important to point out that these same questions are central to many of the 
concerns that several EC Member States have raised .  These are the types of questions that sometimes 
suggest the need for further research, which takes time, resources, and multidisciplinary 
collaborations.  The last sentence of paragraph 133 does not acknowledge that important scientific 
information about environmental consequences could be lacking in specific cases, in which case 
further scientific studies would be warranted.   
1223.  The foreseen end product uses of the product are relevant to safety evaluations – this is a 
standard assumption in all risk assessments, so I am not sure what the point of this question is.   WT/DS291/R/Add.6 
WT/DS292/R/Add.6 
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Page H-256 
  
  Question 112:  Please provide an assessment of the statements regarding chronic toxicity testing 
in paragraph 43 of Canada's Third Submission and paragraphs 134-138 of the US 
Supplementary Rebuttal Submission.  What relevan ce does the foreseen end product use(s) 
have in the context of the evaluation of the toxicity of that product?   
Dr. Nutti  
1224.  Answer 112: As I had pointed out in several answers, and based on the Codex Alimentarius 
Guidelines for the Conduct of Food Safety Asse ssment of Foods Derived from Recombinant-DNA 
Plants (CAC/GL 45-2003), paragraphs 34 to 43, A ssessment of Possible Toxicity, we have at 
paragraph 37 that the use of a ppropriate conventional toxicol ogy or other studies on the new 
substance may be necessary if, taking into account its function and exposure,  doubts about the safety of the new substance remain.  My understanding is  that if the toxicological assessment has conducted 
acute gavage studies in mice, homology to known toxins  and allergens  with no indication of adverse 
effects, chronic toxicity tests  shall not be required. 
Question 113:  Please provide an assessment of th e statements regarding the purpose and use of 
whole food studies in paragraphs 142-144 of th e US  Supplemental Rebuttal Submission.  What 
relevance does the foreseen end product use(s) have in the context of using whole food studies in the evaluation of the safety of that product?   
Dr. Nutti  
1225.  Answer 113:  Based on the Codex Alimentarius  Guidelines for the Conduct of Food Safety 
Assessment of Foods Derived from Recombinant-DNA  Plants (CAC/GL 45-2003), paragraphs 53, my 
understanding is that additional animal feeding studi es may be warranted for GM foods if changes in 
the biovailability of the nutrients are expected or if the composition of the GM food is not comparable to conventional food..  My understanding is that if the comparison of the composition of the GM 
product and its conventional counterpart has shown to  be substantially equivalent, the 90 –day oral 
study and at least one more feeding study ( usually  48 day broiler chicken  ) has provided information 
on the consumption of the whole food, the request for multiple whole food studies in different species 
does not have scientific support. 
Question 114:  Please provide an assessment of the statements regarding small random DNA 
insertions and molecular characterization in paragraph 152 of the US Supplemental Rebuttal 
Submission. 
No Answers. 
 
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