ESTABLISHMENT OF THE URUGUAYAN BIOSAFETY FRAMEWORK AND A
REGULATORY PERSPECTIVE OF ENVIRONMENTAL RISK ASSESSMENT FOR
TRANSGENIC CROPS ENGINEERED WITH COMPLEX TRAITS
By
María Alejandra Ferenczi Gardini

A DISSERTATION
Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of
Plant Breeding, Genetics and Biotechnology - Horticulture – Doctor of Philosophy
2013

ABSTRACT
ESTABLISHMENT OF THE URUGUAYAN BIOSAFETY FRAMEWORK AND A
REGULATORY PERSPECTIVE OF ENVIRONMENTAL RISK ASSESSMENT FOR
TRANSGENIC CROPS ENGINEERED WITH COMPLEX TRAITS
By
María Alejandra Ferenczi Gardini

With increasing world population and anticipated impacts of climate change, there is a need
to develop crop varieties that provide increased productivity while preserving biodiversity
and the environment. Genetic engineering is one of the techniques available to be used in
plant breeding for crop improvement. This technology has the potential to generate a broad
range of new products, including organisms with significantly altered morphology and
physiology. Use of these new technologies and the potential impact of the resultant products
have led to a cautious attitude determining that GE crops follow a different regulatory
pathway than new varieties derived from conventional breeding programs. In this thesis I
discuss the establishment of a biotechnology biosafety regulatory system in Uruguay, its
comparison with other systems in the region and the analysis of environmental safety
questions from a regulatory point of view. In recent years the Uruguayan regulatory system
for GE organisms has undergone consolidation in response to political support of
biotechnology. The legal support is based on Decree 353/008 and is slowly progressing to
law. This thesis describes development of an operational system to handle applications
including establishment of an administrative system which supports the risk analysis phases
of risk assessment; risk management; and risk communication; and an operational system for
follow-up actions of monitoring, surveillance and inspection. The Uruguayan approach is
next compared with those of Argentina, Brazil and Paraguay, which together form the
Southern Common Market (MERCOSUR for its acronym in Spanish). The objective was to

identify from divergences new strategies for improvement of the Uruguayan system, and
from commonalities potential approaches for harmonization. Harmonization could
potentially achieve a more efficient and effective framework for the use of economic,
infrastructure and human resources, and avoid problems of asynchronous authorizations.
While difficult to coordinate the approval of GE organisms for commercial use throughout
the region, specific suggestions are proposed with actions toward harmonization. Finally, the
thesis addresses risk analysis for crops engineered with complex traits such as dehydration
stress tolerance. These traits may utilize genes that encode transcription factors, signalling
factors, metabolic pathway enzymes, among others, with the potential to initiate a cascade of
cellular changes that may produce unanticipated effects on plant metabolism, physiology,
and/or development with biosafety implications. As a result, the application review for
environmental biosafety may be more complex as we move from the first wave of genetically
engineered crops, such as insect- or herbicide tolerant crops for which the gene product
directly confers the trait of interest, to crops with more complex traits. It should be noted,
however, that while important to evaluate, pleiotropic effects are not a hazard per se. Rather,
the same ultimate harms must be evaluated, whether those harms arise due to primary effects
of the gene, or pleiotropic or unintended effects. A conceptual framework is developed for
regulators when analyzing environmental risk assessments of transgenic crops with complex
traits. A case study is performed for release of cucumber expressing the Arabidopsis thaliana
dehydration stress tolerance transcription factor gene, CBF, into the Uruguayan environment.

TABLE OF CONTENTS

LIST OF TABLES .................................................................................................................vii
LIST OF FIGURES ................................................................................................................. x
LIST OF ABBREVIATIONS ............................................................................................... xii
CHAPTER I: LITERATURE REVIEW ............................................................................... 1
INTRODUCTION ..................................................................................................................... 1
CURRENT STATUS OF GLOBAL PRODUCTION OF GENETICALLY ENGINEERED
CROPS ....................................................................................................................................... 5
New genes and trends ................................................................................................................ 8
New traits and trends ................................................................................................................. 9
New crops and trends ............................................................................................................... 12
New environments and trends .................................................................................................. 14
ENVIRONMENTAL RISKS FOR CONSIDERATION WHEN ANALYZING
GENETICALLY ENGINEERED CROPS .............................................................................. 15
Potential ultimate harms .......................................................................................................... 16
Weediness and invasiveness ........................................................................................ 16
Negative effect on non-target organisms ..................................................................... 18
Processes that may result in environmental harms .................................................................. 19
Gene flow ..................................................................................................................... 19
Secondary unexpected effects ...................................................................................... 21
Changes in agricultural practices ................................................................................. 24
GENETICALLY ENGINEERED CROPS AND A BIOSAFETY FRAMEWORK .............. 25
Why regulate genetically engineered crops? ........................................................................... 25
How to regulate genetically engineered crops? ....................................................................... 27
Specialty crops regulatory challenges ...................................................................................... 30
RISK ANALYSIS METHODOLOGY.................................................................................... 34
Risk assessment ....................................................................................................................... 39
Risk management ..................................................................................................................... 51
Risk Communication ............................................................................................................... 52
PROBLEM FORMULATION................................................................................................. 53
CONCLUSIONS AND OBJECTIVES ................................................................................... 64
APPENDIX .............................................................................................................................. 67
REFERENCES ........................................................................................................................ 70
CHAPTER II: ESTABLISHMENT AND ANALYSIS OF THE URUGUAYAN
REGULATORY SYSTEM FOR GENETICALLY ENGINEERED CROPS ................. 84
INTRODUCTION ................................................................................................................... 84
HISTORICAL EVOLUTION OF THE BIOSAFETY REGULATORY FRAMEWORK ON
GENETICALLY ENGINEERED ORGANISMS IN URUGUAY ......................................... 84
CURRENT REGULATORY FRAMEWORK ........................................................................ 91
Criteria and characteristics of its implementation ................................................................... 91
Scope. “Biosafety” restricted to GE plants .................................................................. 92
Process based ............................................................................................................... 93
Risk analysis methodology .......................................................................................... 94
iv

Case by case ............................................................................................................... 103
Step by step ................................................................................................................ 110
Iterative but independent............................................................................................ 114
Open, transparent and documented ............................................................................ 115
Risk Assessment phase .......................................................................................................... 115
Scope .......................................................................................................................... 118
Case by case ............................................................................................................... 119
Step by step ................................................................................................................ 122
Comparative analysis based on familiarity and substantial equivalence ................... 122
Analysis guided by areas of concerns ........................................................................ 124
Hierarchical decision tree and Weight of evidence ................................................... 127
Additional studies performed locally ......................................................................... 127
Persistence and invasiveness of the GM plant or its compatible relatives ................ 128
Interaction of the GE plant with non-target organisms. ............................................. 128
Efficacy studies .......................................................................................................... 129
Underlying criteria applied in the establishment of the Uruguayan biosafety framework .... 132
Issues of the current agenda ................................................................................................... 139
Approach for the regulation of coexistence ............................................................... 139
Landraces ................................................................................................................... 144
Adventitious presence ................................................................................................ 145
Prohibition of sweet corn ........................................................................................... 145
Insect resistance management .................................................................................... 146
Monitoring/Surveillance ............................................................................................ 147
Distinction of Uruguay as “Natural Country” ........................................................... 147
SUMMARY OF THE PROGRESSIVE EVOLUTION OF THE URUGUAYAN
REGULATORY SYSTEM .................................................................................................... 148
Evolution of the basic components of a biosafety framework ............................................... 148
Analysis of applications received by the evolving Uruguayan regulatory system ................ 152
Summary and future directions .............................................................................................. 158
APPENDIX ............................................................................................................................ 160
REFERENCES ...................................................................................................................... 178
CHAPTER III: COMPARISON OF THE URUGUAYAN REGULATORY SYSTEM
FOR GENETICALLY ENGINEERED CROPS WITH OTHER NATIONAL AND
REGIONAL SYSTEMS AND POTENTIAL FOR HARMONIZATION ..................... 187
INTRODUCTION ................................................................................................................. 187
GENERAL DESCRIPTION OF BIOSAFETY FRAMEWORKS........................................ 188
Description of the Argentinean biosafety framework ............................................................ 188
Comparison between the Argentinean and Uruguayan regulatory systems .............. 193
Description of the Brazilian biosafety framework ................................................................. 196
Comparison between the Brazilian and Uruguayan regulatory systems ................... 202
Description of the Paraguayan biosafety framework ............................................................. 204
Comparison between the Paraguayan and Uruguayan regulatory systems ............... 209
COMMON AND DISTINCT ELEMENTS FOUND ACROSS THE MERCOSUR
COUNTRIES ......................................................................................................................... 210
REASONS FOR THE NEED OF HARMONIZATION AND ATTEMPTS THAT HAVE
BEEN MADE ........................................................................................................................ 226
SUGGESTIONS FOR FURTHER PROGRESS TOWARDS A REGIONAL SYSTEM .... 231
Regional Ad hoc Group on agricultural biosafety of GE organisms ..................................... 232
Regional advisory body for food and feed safety assessment ............................................... 235
v

Regional coordinated system for contained field trials.......................................................... 236
APPENDIX ............................................................................................................................ 241
REFERENCES ...................................................................................................................... 249
CHAPTER IV: APPLICATION OF THE PROBLEM FORMULATION APPROACH
WHEN ASSESSING ENVIRONMENTAL RISKS OF CROPS ENGINEERED WITH
COMPLEX TRAITS - A CASE STUDY OF DEHYDRATION STRESS TOLERANCE
IN CUCUMBER .................................................................................................................. 255
INTRODUCTION ................................................................................................................. 255
PROBLEM CONTEXT ......................................................................................................... 256
Protection goals ...................................................................................................................... 259
Environmental scope .............................................................................................................. 260
Baseline information .............................................................................................................. 261
PROBLEM DEFINITION ..................................................................................................... 262
Agronomic harms related to weediness ................................................................................. 262
Agronomic harm: The GE crop itself becomes a weed in agricultural systems
(harm 1). ..................................................................................................................... 262
Agronomic harm: Gene flow from pollen to weedy relatives causing more aggressive
weedy relatives (harder to kill, population expansion) (harm 2) ............................... 266
Agronomic harms related to a negative effect on organisms ................................................. 269
Agronomic harm: The gene product is toxic to non-target organisms (harm 3) ....... 269
Agronomic harm: Negative effect on organisms due to changes in agricultural
practices (harm 4) ...................................................................................................... 273
Agronomic harm: Development of resistance to products that confer herbicide or
insect protection (harm 5) .......................................................................................... 276
Agronomic harms related to a negative effect on soil functions ........................................... 277
Agronomic harm: The gene product is toxic to soil microorganisms (harm 6) ......... 277
Agronomic harm: Negative impact on soil physical properties and soil
microorganisms due to changes in agricultural practices (harm 7) ........................... 277
Ecological harms related to negative effects on natural resources ........................................ 279
Ecological harm: The GE crop itself becomes an invasive species in natural habitats
(harm 8) ...................................................................................................................... 279
Ecological harm: Gene flow from pollen to wild relatives causing one of the
following: wild relatives increase/become invasive or decrease abundance/extinct
(harm 9) ...................................................................................................................... 280
Ecological harm: The gene product is toxic to non-target species (insects and soil
microorganisms) (harm 10)........................................................................................ 282
Ecological harm: Destruction of the natural resource soil due to a change in cultural
practices (harm 11) .................................................................................................... 282
Ecological harm: Destruction of refuge areas due to agricultural expansion over
natural environments (harm 12) ................................................................................. 282
Commercial harms related to negative effects on trade ......................................................... 286
Commercial harm: Negative economic impacts to conventional or organic crops due
to gene flow (harm 13) ............................................................................................... 286
Commercial harm: Negative economic impacts to conventional or organic crops due
to seed mixing (harm 14) ........................................................................................... 290
SUMMARY OF PROBLEM FORMULATION ................................................................... 291
APPENDIX ............................................................................................................................ 296
REFERENCES ...................................................................................................................... 298

vi

LIST OF TABLES

Table 1.1.

Commercial approvals in soybean and corn in the countries of the
Southern Common Market (MERCOSUR) ): Brazil (BRA), Argentina
(ARG), Uruguay (URU) and Paraguay (PAR)…………..…………........

7

Table 1.2.

Percentage of main traits out of the total GE crops planted in 2012……. 10

Table 1.3.

Percentage of traits of the total field trials by year…………………….... 11

Table 1.4.

Elements necessary for the implementation of the decision-making
procedure (modified from UNEP, 2005)……………………………….... 28

Table 1.5. Proposals of the Pew Initiative on Food and Biotechnology Workshop,
2007. Updated by personal communication with S.L. McCammon,
Ph.D., Science Advisor, Office of Science Biotechnology Regulatory
Services, Animal and Plant Health Inspection Service APHIS-USDA,
2010, 2013…………………………………………………………………. 33
Table 1.6. Guideline documents about risk analysis and/or its components,
modified from Hill and Sendashonga (2003)…………….......................... 37
Table 1.7. Terminology used in the literature for risk analysis considered
synonymous in the context of this thesis………………………………….. 43
Table 1.8. Examples of association between hazards, harms and possible
consequences with regard to GE plants………………………………….... 47
Table 1.9. Sequential steps of risk assessment process, problem formulation
approach and scientific method……………………………………………. 54
Table 1.10. General scheme to state particular pathways with the steps for
a harm to occur according to Raybould (2010)……….………………..... 59
Table 1.11. Schematic representation of statistical Type I error and Type II
error applied in risk assessment………………………………………….. 62
Table A1.1. List of crops with commercial approval, number of events and
traits description…………………………………………………………… 67
Table 2.1.

Evolution of the Uruguayan regulatory framework on biosafety
of genetically engineered crops………………………………………….. 87

Table 2.2.

General criteria of the Uruguayan biosafety framework………………...

92

Table 2.3.

Evolution in the establishment of bodies involved in the
Uruguayan regulatory system from 1995 to present…………………... ..

96

vii

Table 2.4.

Applications submitted between 2009 and 2011 by event for
the two categories, National Register of Cultivars (NRC) and
deregulation, or one of the two…………………………………………... 106

Table A2.1. Summary of applications from the period of 1995-2011 by crop,
event, trait, gene, year of application and authorizing agency…………... 160
Table A2.2. Specific information required in the Uruguayan application form
for the areas of concerns of molecular characterization, food safety
and environmental security (Parts B, C and D of the form)………….... .. 167
Table A2.3. Summary of the number of applications in the period 1995-2011
by uses, crop, trait, gene, event, total applications and permits
issued…………………………………………………………………...... 174
Table 3.1.

List of Argentinean specific regulations for GE organisms…………...... 189

Table 3.2.

List of Brazilian specific regulations for GE organisms………………… 198

Table 3.3.

List of Paraguayan specific regulations for GE organisms……………. .. 206

Table 3.4.

Common and different elements analyzed among the biosafety
regulatory system of MERCOSUR countries………………………….... 211

Table 3.5.

Comparative description of the regulatory systems of the
MERCOSUR countries: Argentina (ARG), Brazil (BRA),
Paraguay (PAR) and Uruguay (URU)…………………………………… 215

Table 3.6.

Average of applications approved per year in the period
1995-2011 by category of use and country……………………………… 220

Table 3.7.

Events approved for commercial use (deregulated) by crop
in the MERCOSUR countries…………………………………………… 224

Table A3.1. List of institutions represented on the advisory bodies by country……. .. 241
Table 4.1.

Potential environmental harms that may be associated with GE crops…. 258

Table 4.2.

Uruguayan laws related to environmental protection…………………..... 259

Table 4.3.

Harm 1: Exposure pathway and risk hypotheses to characterize
harm 1 of Table 4.1 regarding weediness in agricultural systems
of the GE crop……………………………………………………………. 263

Table 4.4.

Harm 2: Exposure pathway and risk hypotheses to characterize
harm 2 of Table 4.1 regarding generation of more aggressive
weedy relatives……………………………………………………….….. 267

Table 4.5.

Harm 3: Exposure pathway and risk hypotheses to characterize
viii

harm 3 of Table 4.1 regarding toxicity of the gene product on
non-target organisms…………………………………………………….. 270
Table 4.6.

Exposure pathway and risk hypotheses to characterize harm 4 of
Table 4.1 regarding the GE crop to change cultivation practices that
negatively affect the agroecosystem…………………………………….. 274

Table 4.7.

Exposure pathway and risk hypotheses to characterize agronomic
harm 5 of Table 4.1 regarding resistance development to gene
products that confer herbicide or insect protection……………………… 276

Table 4.8.

Exposure pathway and risk hypotheses to characterize harm 7
of Table 4.1 regarding the GE crop to change cultivation
practices that negatively impact on soil physical properties
and soil microorganisms………………………………………………… 278

Table 4.9.

Exposure pathway and risk hypotheses to characterize harm 8
of Table 4.1 regarding the GE crop itself becoming an invasive
species in natural habitats……………………………………………….. 280

Table 4.10. Exposure pathway and risk hypotheses to characterize harm 9b
of Table 4.1 regarding gene flow form pollen to wild relatives
becoming invasive……………………………………………………….. 281
Table 4.11. Exposure pathway and risk hypotheses to characterize ecological
harm 12 of Table 4.1 regarding destruction of refuge areas due to
agricultural expansion over natural environments………………………. 283
Table 4.12. Number of growers and area planted of cucumber crop in Uruguay……. 285
Table 4.13. Exposure pathway and risk hypotheses to characterize harm 13
of Table 4.1 regarding adventitious presence of the transgene in
conventional and/or organic crops due to gene flow……………………. 287
Table 4.14. Exposure pathway and risk hypotheses to characterize harm 14
of Table 4.1 regarding adventitious presence of the transgene in
conventional and/or organic crops due to seed mixing………………..… 290
Table 4.15. Possible environmental harms that may require further consideration….. 293
Table 4.16. Summary of Problem Formulation performed in the context of
a hypothetical environmental risk assessment process of GE
cucumber plants engineered for dehydration stress tolerance using
a transcription factor…………………………………………………..…. 294
Table A4.1. Minimum temperatures (°C) from March 15th to April 30th in the south
and north regions of Uruguay in the period 2006 to 2010………………. 296

ix

LIST OF FIGURES

Figure 1.1. Environmental safety considerations for GE crops result from
a complex interplay of factors that vary with crop, gene, trait,
and location………………………………………………………………

1

Figure 1.2. Comparison of deregulated or in an advanced stage of risk analysis
events between the first two decades of the genetically engineered
technology (1996-2005 and 2006-2015)………………………………...

3

Figure 1.3. Schematic representation of risk estimation as a function of probability
of harm X consequences if harm happens. The probability of harm to
occur depends on the hazard X likelihood of exposure…………………. 48
Figure 1.4. Summary diagram of Type I and II errors………………………………. 63
Figure 2.1. Diagram of the operating structure of the Uruguayan biosafety
framework according to Decree No. 353/008…………………………...

98

Figure 2.2. Diagram of the operating structure of the Uruguayan biosafety
framework according to Decree No. 353/008 with steps followed
by an application for the risk analysis process………………………… .. 112
Figure 2.3. Environmental safety considerations for GE crops result from
a complex interplay of factors that vary with crop, gene, trait, and
location………………………………………………………………… .. 120
Figure 2.4. Number of application forms entered into the system by category
of use between 2009 and august of 2011 and total number of
applications per year…………………………………………………...... 155
Figure 2.5. Scheme of the evolution of the number of application forms entered
by year and by period of the regulatory system……………………..….. 156
Figure 3.1. Scheme of the Argentinean Biosafety Framework design.
The specific advisory bodies that compose the regulatory
system and exclusively develop related tasks are indicated
in dark shading. Divisions that collaborate with the regulatory
system for particular tasks are indicated in light shading……………..... 192
Figure 3.2. Scheme of the Brazilian Biosafety Framework design.
The specific advisory bodies that compose the regulatory
system and exclusively develop related tasks are indicated
in shading.................................................................................................. 197
Figure 3.3. Scheme of the Paraguayan Biosafety Framework design.
The specific advisory bodies that compose the regulatory system
x

and exclusively develop related tasks are indicated in shading……….. .. 208
Figure 3.4. Accumulated number of commercial approvals over the period
from 1995-201 in MERCOSUR countries……………………………… 222
Figure 3.5. Total number of commercial approvals per year in MERCOSUR
countries from 1995 to 2011…………………………………………..... 223
Figure 4.1. Scheme of interconnection between factors that determine possible
environmental concerns: the crop, gene, trait and location of the study
case (Schematic derived from Grumet et al., 2011)…………………… .. 257

xi

LIST OF ABBREVIATIONS

ANII:

National Agency of Research and Innovation

CAAR:

Advisory Committee for Risk Analysis

CAI:

Institutional Coordination Committee

CECTE:

Committee of Ethics in Science and Technology (Argentina)

CERV:

Commission on Risk Assessment of Genetically Engineered Plants

CGR:

Risk Management Commission

CIBIO:

Internal Biosafety Commission (Brazil)

CNBS:

National Biosafety Council (Brazil)

COMBIO:

Agricultural and Forestry Biosafety Commission, (Paraguay)

CONABIA:

National Advisory Commission on Agricultural Biotechnology (Argentina)

CTAUOGM: Technical Advisory Committee on the Use of Genetically Modified Organisms
CTNBIO:

National Biosafety Technical Commission (Brazil)

DGSA:

General Direction of Agricultural Services

DGSPA:

General Direction of Agricultural Protection Service

DMA:

Directorate of Agrifood Markets (Argentina)

DPA:

Division of Agricultural Protection

ERB:

Biosafety Risk Assessment

GIM:

Interministries Working Group created by Decree No. 037/007

GNBio:

National Biosafety Cabinet

GTA:

Working Group on legal aspects

GTE:

Working Group on labeling

GTI:

Working Group on institutions

GTP:

Working Group on public participation

xii

IIBCE:

Biological Research Institute Clemente Estable

INASE:

National Institute of Seeds

INIA:

National Institute of Agriculture Research

IP:

Institute Pasteur of Montevideo

LATU:

Technological Laboratory of Uruguay

MAG:

Ministry of Agriculture and Livestock (Paraguay)

MAGYP:

Ministry of Agriculture, Livestock and Fisheries (Argentina)

MEC:

Ministry of Education and Culture

MEF:

Ministry of Economy and Finances

MERCOSUR: Southern Common Market among Argentina, Brazil, Paraguay and Uruguay.
MGAP:

Ministry of Livestock, Agriculture and Fisheries

MINCYT:

Ministry of Science, Technology and Innovation (Argentina)

MSP:

Ministry of Public Health

MVOTMA:

Ministry of Housing, Land and Environment

NBF:

National Biosafety Framework

OERF:

Registration and Monitoring Bodies and Entities (Brazil)

RR:

Round-up Ready

SAGYP :

Secretary of Agriculture, Livestock and Fisheries (Argentina).

SEAM:

Secretary of Environment (Paraguay)

SENACSA:

National Service of Quality and Plant Health and Seeds (Paraguay)

SENASA:

National Health Service and Food Quality (Argentina)

SENASA:

National Service of Quality and Animal Health before named National Service
of Animal Health (SENASA), (Paraguay)

SENAVE:

National Service of Quality and Plant Health and Seeds (Paraguay)

SIB:

Biosafety Information System (Brazil)

xiii

UDELAR: University of the Republic - public academia

xiv

CHAPTER I: LITERATURE REVIEW

INTRODUCTION
We are approaching a new era of genetically engineered (GE) crops which will
involve an increased variety and complexity of types of genes and phenotypes incorporated
into new crops and planted in new locations. Environmental safety considerations for GE
crops vary with crop, gene, trait and location and result from a complex interplay of each of
the factors (Figure 1.1).

Figure 1.1. Environmental safety considerations for GE crops result from a complex interplay
of factors that vary with crop, gene, trait, and location. (Figure from Grumet et al., 2011).
Changes are observed when comparing the first decade of commercially approved
biotech crops “1996-2005” with the second decade “2006-2015” (Figure 1.2). New types of
genes whose mode of action differs from those of the first wave of transgenic crops include
genes that encode transcription factors, signal transduction pathway and metabolic enzymes.
New traits under development include resistance to biotic and abiotic stresses, increase in
valuable compounds, improved availability of nutrients, or a decreased concentration of
undesirable substances. New crops include some non-commodity crops such as horticultural
species, and ‘orphan crops’ that have received little breeding or biotechnology attention. As
different regions of the world begin to grow these crops, and new kinds of crops are grown,
new locations and environmental conditions also will be encountered.
1

To date, commercially produced GE crops were almost exclusively developed by U.S.
or European private corporations and first cultivated in the US and other countries which are
producers of those crops, such is the case of soybean in South America or canola in Canada
(James, 2012). Additionally the private developer also applied for regulatory approval in
strategic countries that import the product as food and/or feed, such as countries of the
European Union and Japan (Stein and Rodriguez-Cerezo, 2009). However many developing
and transitioning countries whose economies rely on agriculture are incorporating
biotechnology and molecular plant breeding in their national plans, to find solutions for
increasing national and regional demand for food security and to satisfy global needs for a
more productive agriculture (James, 2012).
GE crops are being developed by public national providers in Asia and Latin America
designed specifically to solve local agricultural problems and to be commercialized in
domestic markets. For example, in Brazil a public/private association between the private
companies BASF together with the National Agricultural Research Institute EMBRAPA led
to the development of transgenic soybean with tolerance to the herbicide imidazolinona that
was approved for commercial release by the Brazilian government in 2009 (Brazil, CTNBio,
2009). More recently the public sector institution EMBRAPA has developed and obtained
commercial regulatory approval of GE Phaseolus beans with virus resistance (Brazil,
CTNBio, 2012). Other examples include Bt brinjal (eggplant) in India, Bt rice and phytase
maize in China which has been approved for field trials, Bt maize in Cuba that was planted
3,000 hectares as “regulated commercialization”, as well as other examples under
development in Cuba, Argentina, and Chile (Cohen, 2005; Grumet et al., 2011; James, 2011,
2012). Bt eggplant in India is being developed through a private-public partnership (between
Monsanto (Mahyco) and the public sector), while a water efficient maize project in Africa is
being performed in partnership with the Bill and Melinda Gates Foundation (James, 2011).

2

Figure 1.2. Comparison of deregulated or in an advanced stage of risk analysis events
between the first two decades of the genetically engineered technology (1996-2005 and 20062015).
3

Bt rice and phytase maize in China have been developed entirely by the public sector,
the Chinese Agricultural Academy of Sciences (CAAS). Other examples of China include
Beijing University Bt poplar developed by the Research Institute of Forestry and Beijing
virus resistance sweet pepper (PK-SP01) developed by the Beijing University (ISAAA
homepage, 2013). Bt maize in Cuba with resistance to a major local pest (Spodoptera
frugiperda) has been developed by the Havana-based Institute for Genetic Engineering and
Biotechnology (CICB) (James, 2012). The technology used by Monsanto and BASF to
develop the drought tolerant transgenic maize, that will be commercially released in the US
in 2013, was donated to a Private/Public sector partnership (WEMA) of sub-Saharan Africa
to develop a biotech drought tolerant maize expected for 2017 (James, 2012). Other countries
including the Philippines, Bangladesh, Vietnam, Malaysia, Thailand, Egypt, Kenya, South
Africa, Mexico, Costa Rica, have records of official field trials of GE plants conducted with a
variety of species (Nap et al., 2003; Toenniessen et al., 2003; James, 2011).
As these sorts of projects involving new kinds of technologies are undertaken by an
increasing number of countries throughout the world, the necessary regulatory systems must
also be developed and adapted. In this thesis I discuss the establishment of a biotechnology
biosafety regulatory system in Uruguay and the analysis of environmental safety questions
from a regulatory point of view. Specific portions of the literature review are from “Future
possible genetically engineered crops and traits and their potential environmental impacts”
Grumet R, Wolfenbarger L and Ferenczi A. pp. 47-57 and “Systems to regulate genetically
engineered plants. Similarities and differences among countries” Hokanson K and Ferenczi
A. pp. 147-155 of “Environmental safety of genetically engineered crops” 2011. 234p.

4

CURRENT STATUS OF GLOBAL PRODUCTION OF GENETICALLY
ENGINEERED CROPS
Since the first commercially released transgenic crops were planted in the United
States in 1996 the total area planted has been constantly increasing, reaching 170.3 million
hectares in 2012 (James, 2012). This represents approximately 11.3% of the 1.5 billion
hectares of total arable land area worldwide (James, 2011). In 2012 twenty eight (28)
countries cultivated GE crops; an additional 31 countries have regulatory approvals for
import for food and feed use (James, 2012). The area planted by the 28 countries varies
substantially, with 17 countries that plant 50,000 or more hectares. Rapid adoption occurred
primarily in countries such as US and Canada in North America; Brazil, Argentina, Paraguay
and Uruguay in South America; South Africa in Africa; and China and India in Asia. These
are all countries that are major producers of one or more of the handful of primary GE crops,
cotton, soybean, maize and canola.
Several Latin American countries are currently producing GE crops. In the countries
of the Southern Common Market (MERCOSUR for its acronym in Spanish), there is
currently political support for biotechnology. Brazil is the country with the highest number of
commercial approvals (36), followed by Argentina (28), Uruguay (14) and Paraguay (6).
Uruguay is in the tenth position worldwide with an estimated 1.3 million hectares of total GE
crops. Four events in soybean and ten events in corn have been approved for planting and
commercialization since 1996 (URUGUAY, GNBio homepage 2013). In the season 2011-12,
approximately 900,000 ha of soybean were planted, with 100% GE varieties, and about
120,000 ha of corn, with an estimated 60- 90% GE varieties (Souto, 2010; Uruguay, MGPADIEA, 2012). In Brazil, not only the area, but also the number of events approved recently
has increased, reaching five in soybean, eighteen in corn, twelve in cotton and one in bean
(Brazil, CTNBio, 2013). Argentina also has changed its regulatory system to improve its

5

efficiency and has already increased the number of events with regulatory approval having
approved five in soybean, twenty in corn and three in cotton (Argentina, CONABIA, 2013).
Paraguay for its part also has recently adjusted its regulatory system having approved four
commercial events in corn and one in soybean (Paraguay, CONBIO, 2013). Table 1.1
compares the commercial approvals in soybean and corn, which are the crops planted in
Uruguay, within the countries of MERCOSUR.
Other Latin American countries also support transgenic technology. The case of
Mexico approving transgenic maize for field trials is particularly interesting. As Mexico is a
center of origin for maize, there are additional challenges for the regulatory system regarding
monitoring and control to avoid possible environmental harms due to gene flow through
pollen (Ortiz, 2011). Costa Rica recently approved transgenic crops, not for internal market,
but for seed export. Chile currently produces seed for export and is now adjusting its
biosafety framework to include commercial production of GE crops (Teresa Agüero, 2011).
The government of Chile has the will to approve transgenic crops for domestic production,
and also foresees potential to release their own transgenic crops solving specific local
problems. Research institutions in Chile have developed several projects that are being tested
under contained conditions. Commercial release of GE crops can be a disadvantage for the
seed industry by creating potential problems with adventitious and low level presence.
Currently there is only transgenic seed export production under strict biosafety controlled
conditions that is concentrated in a specific area of the country for this purpose.

6

Table 1.1.Commercial approvals in soybean and corn in the countries of the Southern
Common Market (MERCOSUR): Brazil (BRA), Argentina (ARG), Uruguay (URU) and
Paraguay (PAR).

Event/Crop

BRA
ARG
URU
PAR
Events in soybean
40-3-2 (Ht1)
1998
1996
1996
2004
BPS-CV127-9 (Ht3)
2009
2013
----A2704-12 (Ht2)
2010
2011
2012
--A5547-127 (Ht2)
2010
2011
2012
--MON89788X87701 (Ht1xIr1)
2010
2012
2012
2013
Events in corn
176
--1998
----T25 (Ht2)
2007
1998
----MON810 (Ir1)
2007
1998
2003
2012
BT11 (Ir1,Ht2)
2007
2001
2004
2012
NK603 (Ht1)
2008
2004
2011
--GA21 (Ht1)
2008
2005
2011
--TC1507 (Ir1,Ht2)
2008
2005
2011
2012
MIR162 (Ir1)
2009
2011
----MIR604 (Ir2)
--2012
----MON89034 (Ir1)
2009
2010
-----MON88017 (Ir2,Ht1)
2010
2010
----DP-098140-6 (Ht1, Ht4)
--2011
----MON810XNK603 (Ir1xHt1)
2009
2007
2011
--BT11XGA21 (Ir1,Ht2xHt1)
2009
2009
2011
--TC1507XNK603 (Ir1,Ht2xHt1)
2009
2008
2012
--TC1507XMON810 (Ir1,Ht2xIr1)
2011
------MON89034XNK603 (Ir1xHt1)
2010
2012
----MON89034XMON88017 (Ir1xIr2,Ht1)
2011
2010
--2012
BT11XMIR162XGA21 (Ir1,Ht2xIr1xHt1)
2010
2011
2012
--MON89034XTC1507XNK603 (Ir1xIr1,Ht2xHt1) 2010
2012
2012
--TC1507XMON810XNK603 (Ir1,Ht2xIr1xHt1)
2011
------(1)
BT11XMIR162XMIR604XGA21
------2012
(Ir1,Ht2xIr1xIr2xHt1)
(1) Intermediate combinations are also approved.
Ht = herbicide tolerance (1: glifosate; 2: glufosinate; 3: imidazolinones; 4: acetolactato
sintasa)
Ir = insect resistance (1: lepidopteran; 2: coleopteran)
Source of data: National Biosafety Technical Commission (CTNBio), Brazil,
http://www.ctnbio.gov.br/index.php/content/view/12482.html; National Advisory
Commission on Agricultural Biotechnology (CONABIA), Argentina,
http://64.76.123.202/site/agregado_de_valor/biotecnologia/55OGM_COMERCIALES/index.php; National Biosafety Cabinet (GNBio), Uruguay
http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,1,144,O,S,0,MNU;E;121;6;MNU;,;
Agricultural and Forestry National Biosafety Commission (CONBIO), Paraguay,
http://www.mag.gov.py:1082/conbio/.

7

Other Latin American countries have chosen not to produce GE crops. Peru adjusted
its biosafety framework in 04/15/2011, when the Ministry of Agriculture established a new
Decree, No. 003/2011 (Perú, 2011a). Soon after the promulgation of Decree No. 003/2011
agricultural associations requested that it be revoked. Law No. 29811 was then promulgated
establishing a moratorium on GE crops (Perú, 2011b). Since November 2012 Peru has
entered a moratorium for ten years prohibiting the use of GE organisms (Peru, 2012).
However, GE organisms for research in contained trials for pharmaceutical and veterinary
GE products and GE products imported for food and feed are excluded from the moratorium
(Peru, 2012). Bolivia has approved herbicide tolerant soybean, but there is ambiguity
between a political will to achieve food security by profiting from protecting biodiversity or
by supporting production of transgenic crops (Personal Communication, Ing. Agr. Enzo
Benech, Subsecretary of the Ministry of Agriculture, Uruguay 2012).

New genes and trends
Many of the new types of traits that are being developed arise from different kinds of
genes than were used for the first wave of GE crops. The first wave of transgenic crops
primary utilized genes whose protein product was directly responsible for the desired trait
(e.g., Bt proteins confer insect resistance; herbicide resistance genes encode proteins that
prevent binding of the herbicide or otherwise inactivate the herbicide) (Carpenter et al.,
2002). These protein products are largely inert with respect to other cellular functions.
Possible pleiotropic or epistatic effects are more likely to be due to a position effects rather
than gene function.
In contrast, the function of many of the newer genes being tested is to initiate other
changes within the cell. They may cause the cell to produce needed compounds to survive,
grow and respond to the environment. Such genes may encode transcription factors that
8

regulate expression of other genes; they may code for signaling factors that initiate response
to perceived changes in the cellular environment; or they may produce metabolic pathway
enzymes that result in the production of new cellular compounds. Examples include
transcription factor genes that have been used to modulate floral development or abiotic
stress resistance; signaling or hormonal factor genes that have been used to initiate responses
to invading pathogens or modify fruit ripening; and metabolic pathway genes that have been
used to modify oil, carbohydrate, or amino acid composition (Figure 1.2).
As a result of their downstream actions, these types of genes would be expected to
have broader effects on plant metabolism, physiology, and development than genes for which
the protein itself is the final end product (Wolfenbarger and Grumet, 2002; Little et al., 2009;
Chan et al. 2011; Grumet et al., 2011). Indeed, it is the ability of these kinds of genes to
initiate a cascade of effects that makes them highly valuable for genetic engineering. A
single gene can achieve what might otherwise take dozens of genes (Thomashow, 2001). At
the same time, however, altered expression of a broad range of genes via introduction of
regulatory, signaling or metabolic genes, also has the potential to modify non-target
phenotypes within the plant through pleitrophic or epistatic interactions (Wolfenbarger and
Grumet, 2002; Little et al., 2009). These changes could, in turn, influence fitness or the
probability of gene flow of the introduced trait.

New traits and trends
The first generation traits, herbicide tolerance and insect resistance, were rapidly
adopted and continue to be the traits with the most regulatory approvals and area planted
(James 2011, 2012). More recently, stacked events with two or three traditional traits
combined have been increasingly adopted, representing 26% of the global area of GE crops
planted in 2012 (Table 1.2).
9

Table 1.2. Percentage of main traits out of the total GE crops planted in 2012.
Trait

Area planted
(million ha)
Herbicide tolerance
93.9
Stacked events
43.7
Insect resistance
23.9
Source: James, 2011, 2012.

Percentage of the global area with
GE crops (160 million ha)
59
26
15

While these first generation GE traits dominate current commercial production,
information from field trials can be used as an indicator of which new genes, traits and crops
will likely reach the market in the future. Several factors will determine if a GE crop will
reach production stage including the success of the trait in conferring the desired phenotype,
concerns of consumer opposition, and numerous market issues regarding anticipated adoption
and profitability of the product. However, as a rough estimation, field trial data provide a
“biotech observatory” that regulatory systems can use to monitor what may come in the near
future.
An OECD (2009) report indicates that agronomic and product quality traits have
received increasing attention in recent years, while trials for the first generation trait,
herbicide tolerance, stayed constant and insect resistance trials declined. Stein and
Rodriguez-Cerezo (2009) predict that insect resistance and herbicide tolerance will still be
dominant traits by 2015 but that new agronomic and quality traits will also be available.
Trials for product quality traits have remained stable over the past 15 years at about 13%
(Table 1.3).
The agronomic traits category refers to plant growth, development and performance
traits (growth rates, earliness by altered flowering, yield enhancement, fruit ripening) and
environmental or abiotic stress tolerances (frost, cold, heat, drought, salinity) (Wolfenbarger
and Grumet, 2002). Agronomic traits that are currently being incorporated include higher
nitrogen use efficiency as well as drought and cold tolerance (OECD, 2009; Grumet et al.,

10

2011; James, 2011, 2012). In 2009 a new event, MON87460-4, conferring drought tolerance
in corn, was submitted for review. The gene introduced, cspB from Bacillus subtilis, is an
RNA chaperone that preserves RNA secondary structure during conditions of environmental
stresses (Castiglioni et al., 2008). The resulting phenotype in corn is a reduction in yield loss
when the GE plant is under water-limited conditions compared to the conventional crop
(Monsanto, 2009). Drought tolerant sugarcane could also be released in Indonesia in a near
future (James, 2012).
Table 1.3. Percentage of traits of the total field trials by year.
Trait/Year
1997
2007
2011
Herbicide Tolerance
30.0%
22.3%
19.2%
Insect Resistance
20.3%
19.7%
8.65%
Virus Resistance
13.6%
1.8%
1.33%
Agronomic Properties
7.13%
21.5%
32.0%
Product Quality
14.35%
13.9%
13.5%
Total number of field trials 1066
2018
2565
Source: Information Systems for Biotechnology, Virginia Tech
http://www.isb.vt.edu/, 2012.

More recently the event MON87712-4 incorporating the BBX32 gene from
Arabidopsis thaliana to confer enhanced yield in soybean was submitted for deregulation in
2011 (Monsanto, 2011). The BBX32 protein is a member of the B-box zinc finger family
acting as a transcriptional accessory protein assisting the function of transcription factors
through protein-protein interactions (Monsanto, 2011). The BBX32 protein represses plant
responses to the transition from light to dark causing a change in the diurnal metabolism
during the reproductive phase of the soybean plant. These changes result in an extended
period of photosynthetic activity leading to an increased availability of assimilates and higher
yield (Monsanto, 2011). If this event is deregulated would be the first trait for yield
improvement per se, approved for commercialization. Increased yield to date has been
achieved indirectly from events such as pest resistance and herbicide tolerance through
reduced crop losses.
11

Quality traits refer to industrial processing traits and consumer-oriented traits.
Industrial processing traits include improved oils and fatty acid composition, modified
carbohydrates (sugar and starches), proteins and amino acid content and characteristics for
biofuel production. Consumer appeal traits include nutritional quality (vitamins A, E,
protein), reduction in targeted components (nicotine, caffeine, allergens), medical products
(oral vaccines, antibodies and pharmaceuticals) and altered storage and appearance as well as
improvement for animal feed (Wolfenbarger and Grumet, 2002). Some quality categories
could overlap, for example “oil and fatty acids” could include changes in fatty acids for
industrial processing, or in the “animal feed” category could be changes in proteins or
carbohydrates (OECD, 2009). Quality traits that are in the pipe line for commercial use
according to James (2011), include -carotene in rice (golden rice), omega-3 in soybean, high
lysine maize and phytase in maize.
From a regulatory standpoint, it is also important to mention the tendency of stacked
events to replace the single event crops. Stacking refers to combination of multiple events in
one plant by conventional breeding of the original single events. For example, 4-way stacked
maize, which combines eight genes (SmartStax) for above and below grown insect pest
control plus herbicide tolerance for weed control is currently on the market.

New crops and trends
The majority of GE crops that reach the commercial phase are still primarily varieties
of soybean (47% of global biotech area), corn (32%), cotton (15%) and canola (5%) (James,
2011). There are a few examples of horticultural GE crops among the first generation of
transgenic crops which include tomato (FlavrSavr) with delayed ripening (which was the first
approved commercial release transgenic crop in the US in 1994 but it is no longer in the
market); papaya and squash with virus resistance; and carnation in Australia, Japan and the
12

Netherland (Brookes and Barfoot, 2006; ISAAA website, 2013). However, as of 2012, GE
varieties of 25 crops reached commercial regulatory approval (James, 2011, ISAAA website,
2013). These include additional large hectarage crops, like rice and wheat, as well as small
and medium hectare high value-added crops such as sugar beet, melon, plum, tomato, beans
(Table 1 in Appendix).
The number of engineered crops species that have been registered for field trials is
considerably larger than those that have been commercialized. These include safflower,
barley, sugarcane, sunflower, Kentucky bluegrass, lettuce, spinach, cassava, onion,
sweetpotato, pumpkin, eggplant, peas, grapes, banana, apples, olives, nuts, peanuts,
eucalyptus and pine (OECD, 2009; ISB Virginia Tec website, 2012; BCH website, 2013).
Many are important crops for nutrition and income in developing countries, or are local or
regional species outside the international market dynamic and for which there is less attention
from international or regional crop research organizations. However crops such as cassava,
sweetpotato and eggplant are valued culturally, adapted to harsh environments, nutritious and
diverse in terms of genetic background, agroclimatic adaptation and economic niches for
what the potential to extend applications of transgenic technology for these crops
improvement may be significant (Naylor et. al., 2004).
Small-acreages horticultural crops including fruits and vegetables, together with tree
nuts and nursery crops are grouped in what is called specialty crops. Specialty crops have
become increasingly important in the U.S. agricultural economy, exceeding the combined
value of the five major program crops ($49 and $45.8 billion in sales respectively) (USDA
‘Specialty Crop Research Initiative’, Farm Bill 2007). However, from a biotechnology point
of view, these crops face unique challenges. Small-acreages specialty crops do not have the
financial support to face the costs of generating new GE cultivars and the associated
regulatory system costs (Kalaitzandonakes et al., 2007; Moose and Mumm, 2008). There are

13

cases in which engineered crops from this category have already been generated or other
crops may have potential for biotech crop development, but the regulatory system is a clear
limiting factor to reach the commercial phase (US Pew Initiative on Food and Biotechnology,
2007).

New environments and trends
The broader range of traits and crop possibilities brings additional countries into the
biotechnology era increasing the interest across the developing world (Nap et al., 2003;
Grumet et al., 2011; James, 2012). Looking globally the countries as “new environments”, 28
countries were growing GE crops in 2012 (James, 2012). Since 2005 10 new countries have
adopted the technology (Pakistan, Bolivia, Burkina Faso, Myanmar, Chile, Sudan, Cuba,
Egypt, Costa Rica and Slovakia).
Each new country that achieves regulatory approval for GE crops implies a specific
environment to consider in risk assessment. Factors to be taken into account include the
nature of the ecosystem of the receiving environment, whether it is an introduction of a new
cultivar of a currently grown crop or if it is a new crop with a new cropping system, and the
presence of compatible relatives that may allow for gene exchange (Grumet et al., 2011).

14

ENVIRONMENTAL RISKS FOR CONSIDERATION WHEN ANALYZING
GENETICALLY ENGINEERED CROPS
The potential environmental impacts that have been raised for consideration when
releasing transgenic crops include both ecological and agronomic concerns (Snow and Palma,
1997; Grumet and Gifford, 1998; Barton and Dracup, 2000; Conner et al., 2003). Even
though the environmental concerns that are discussed in this thesis are also applicable to
crops developed by traditional plant breeding, they had not received much attention until the
development of genetically engineered crops (Sanvido et al., 2006).
The agronomic concerns relate to increased weediness (invasiveness) either by the GE
plant itself or weedy relatives; possible negative effects on non-target organisms; and negative
effects on soil functions due to change in agricultural practices. The ecological concerns relate
to possible negative effects on natural resources resulting from gene flow to wild relatives
influencing invasiveness or biodiversity, or destruction of refuge areas due to agricultural
expansion. There are other impacts that can be grouped as “commercial” which include impacts
related to gene flow from pollen or due to seed mixing with conventional or organic crop
causing coexistence conflicts. These concerns are discussed in chapter 3 with special emphasis
on GE plants with genes for dehydration stress tolerance. Each type of these harms has been
extensively described in numerous papers and reviews (Keeler, 1989; Snow and Palma, 1997;
Grumet and Gifford, 1998; Barton and Dracup, 2000; Wolfenbarger and Phifer, 2000;
Ellstrand, 2001, 2003; Dale et al., 2002; Conner et al., 2003; Hancock, 2003; Jenczewski et al.,
2003; Pilson and Prendeville, 2004; Hails and Morley, 2005; Snow et al., 2005; Nickson,
2008). A brief description of these potential environmental harms and questions asked in risk
assessment are included below.

15

Potential ultimate harms
Weediness and invasiveness
Weediness and invasiveness are the ultimate concerns of transgenic crops which can
arise as a result of the direct effect of the transgene, as a result of gene flow, or due to
secondary unexpected effects of the transgene. The harms feared are that the crop itself
and/or compatible wild relatives through gene flow, can become more persistent in
agricultural environments (a weed), or can become more invasive in natural habitats
(invasiveness). Gene flow from pollen to wild relatives could also cause decrease abundance
leading to extinction of rare wild relatives. Weediness could result if the GE crop becomes
more aggressive and harder to eliminate (Ellstrand and Hoffman, 1990; Dale, 1992; Hancock
et al., 1996; Barton and Dracup, 2000; Wolfenbarger and Phifer, 2000; Stewart et al., 2003).
The transgene would pose a hazard if it has the capacity to enhance, directly or
indirectly, due to unexpected secondary effects, the ability of the crop or wild relative to
become weedy/invasive. From a regulatory point of view, baseline information about the
biology of the crop, whether compatible wild relatives are present in the receiving
environment, and the phenotypic effect of the transgene on the general plant fitness, are
analyzed in order to determine whether the GE crop and/or wild relative has the potential to
become weedy/invasive (Hancock, 2003).
Hancock (2003) classifies species and transgenes into different categories according
to their invasive potential (species categories) and the fitness impact (transgenes categories).
The environmental risk is the result of the combination of these categories. For example, a
transgene that confers herbicide tolerance will represent a concern for agriculture if it is
engineered in a crop that itself has weedy characteristics or if there is present in that area a
compatible wild relative that already has weedy characteristics. In crops that already have
weedy characteristics, volunteer plants could become weeds in subsequent crops. In the case

16

of crops that have compatible weedy relatives, such as sorghum, canola, wheat, sunflower or
rice (Hancock, 2003; Snow et al., 2003; Stewart et al., 2003), a key question is whether the
transgene persists in the environment after being introgressed into the wild relative genome
(see following section about gene flow). In this example, the transgene for herbicide
tolerance will have a high selective pressure in an environment where that herbicide is
applied.
In the case of invasiveness, the net effect of the trangene on reproductive fitness can
be neutral, detrimental, advantageous or variable depending on the environment and stress
encountered (Ellstrand et al., 1999; Hancock, 2003). Traits that may confer fitness and
competitive advantages to wild relatives include transgenes for biotic or abiotic stressesif
those factors represent a limitation in the wild habitat. The selective pressure for insect and
disease resistance transgenes will depend on the specific levels of natural control in the wild
habitat (Hancock, 2003; Stewart et al., 2003).
Characteristics that have been associated with ability of weeds to spread and persist
outside their natural geographic range include: broad germination requirements, discontinuous
germination (internally controlled) with high seed longevity, a rapid growth through vegetative
phase to reproductive phase, continuous seed production, self-pollination or cross-pollinated
with unspecialized pollinators or wind pollination, very high seed output under favorable
environmental conditions, plasticity in seed production under a wide range of environmental
circumstances, short- and long-distance seed dispersal, vigorous vegetative reproduction,
propagules with brittleness, vigorous competitors, polyploidy (Baker, 1974). While these
characteristics cannot be used to predict weediness (Conner et al., 2003), several are evaluated
at field experiments when comparing the transgenic plant with the non-transgenic plant
counterpart. The characteristics generally included are: seed dormancy, germination, vegetative
growth rate, period of phenological phases to determine life cycle, time to flower, period of

17

seed production and amount of seed produced; persistence of seeds in the soil and presence of
volunteer plants in following season (URUGUAY, GNBio website, 2013). Volunteer plants
could be a way for the transgene to persist in the agroecosystem and eventually allow
hybridization and introgression into wild relatives if they are present in the vicinity and are
sexually compatible.

Negative effect on non-target organisms
Non-target organisms include all other organisms the GE crop may impact, with the
exception of those the crop was engineered to control, if it is intended to confer pest
resistance. The concerns of a negative impact on non-target organisms regarding potential
ecological consequences include a change in food web relationships or a change in ecological
processes that occur in the soil. The impact on non-target organisms can be studied following
a step-wise (tier) approach in which early tier tests are performed in laboratory (GarcíaAlonso et al., 2006; Romeis et al., 2006, 2008).
Non-target organisms are fed with a dose in high excess (e.g., 10-fold) of the level
normally ingested when eating prey that fed on the GE plant or when directly consuming
parts of the GE plant. This approach uses the criterion that if no harm is observed when
ingested at high excess, the risk of a negative impact on non-target organisms at levels
normally encountered in the field would be low. If a risk is identified during the laboratory
tests, the assessment increases in complexity and realism reaching semi-field and field studies
in order to determine its ecological relevance. Risk assessment based only on laboratory
studies has been considered as being ecologically unrealistic and not able to predict largescale and long-term effects (Andow and Hilbeck, 2004; Lovei and Arpaia, 2005). It is
possible that there could be more subtle potential direct and indirect effects of the insecticidal
protein in the plant affecting the non-target organisms, when they interact in the environment
18

(Romeis et al., 2006). Thus, a regulatory authority may require additional field studies
including post release monitoring studies.

Processes that may result in environmental harms
Gene flow
The environmental concern defined as “gene flow” refers to transfer of the transgene
from the GE crop to a wild relative. The dispersal of the transgene itself is not the ultimate
harm to be evaluated. The concern is the phenotypic effect of the transgene if it persists in the
environment (agroecosystem or ecosystem). Possible phenotypic effects of the transgene that
would be of concern for the environment are the ones already discussed: weediness,
invasiveness/ extinction and/or negative impact on non-target organisms, whichever is
applicable (Ellstrand et al., 1999; Conner et al., 2003; Hancock, 2003; Wolfenbarger, 2003;
Weebadde and Maredia, 2011).
Gene flow from pollen happens through the normal sexual reproductive process which
is referred as vertical gene transfer. For gene flow to have an environmental impact, the
transgene must become fixed in the wild relative genome. This requires several steps that may
take years or a few generations. The steps leading to transgene fixation include the presence of
a compatible wild relative in the receiving environment, a crop biology with the ability to form
viable hybrids by cross-pollination, and the ability of the transgene to stably persist in
populations of the wild relative (process of introgression) which will be influenced by the
selective pressure that determines the phenotypic effect of the transgene. If these steps are met,
the critical issue will be to determine whether the introgressed transgene causes ecological
consequences specific to the GE trait.
For hybridization to occur, the primary question is whether there are sexually
compatible relatives in the vicinity of the GE crop. If relatives are present, additional factors
19

such as flowering times, rate of out-crossing and self-pollination, rate of pollen dispersal,
pollen viability and longevity, wind speed and direction, pollinating agents and their
characteristics, distance between GE crop and receiving species, plot size and wild population
density, frequency and distribution, will influence the rate of occurrence of hybridization.
Subsequent to cross pollination, the resultant hybrid seeds must be viable and able to
germinate in the recipient environment. The F1 progeny must, in turn, produce flowers and
further hybridize with the wild relative to form backcross hybrids, allowing for introgression
of the transgene (Ellstrand et al., 1999; Stewart et al., 2003). Finally, the backcross hybrids
must survive and reproduce through several generations until the transgene persists in
populations of the wild relative (Conner et al., 2003; Stewart et al., 2003).
According to the factors that influence hybridization and introgression, from a
regulatory point of view, analysis includes baseline information about proximity to
compatible wild relatives, the biology of the crop, and their invasive characteristics, and the
phenotypic effect of the transgene on their fitness (Cook, 1999; Hancock, 2003). From the
breeding literature we can get information such as which wild species are compatible with
specific crops as well as the center of origin and geographical distribution of wild species
(Hancock, 2003). Crop biology considerations include: reproductive barriers (breeding
system: inbreeding or outcrossing crop), modes of pollination, methods of seed dispersal
(natural and through agricultural activity), coincidence in flowering times, and hybrid
viability (fertility of hybrids) (Ellstrand et al., 1999; Raybould and Gray, 1993; Hancock et
al., 1996). If hybridization is confirmed, information regarding proximity (frequency and
distribution) to wild relatives and size of populations within the area where the GE crop will
be cultivated is used to determine appropriate isolation distances in order to manage gene
escape to minimize hybrid frequency.

20

In most cases, if the gene does not confer a selective advantage, the hybrids usually
survive for only one season. Presence of the transgene in wild populations would result from
a continuing flux of new volunteers but not due to an introgression event (Conner et al.,
2003).
Gene flow from pollen could be also a concern regarding the presence of non-GE
conventional crops in the receiving environment when coexistence regulation exists. In this
case, the dispersal of the transgene in itself is the ultimate harm to be evaluated although the
phenotypic effect of the transgene does not cause harm to the environment. In this regard, gene
flow can also happen through seed mixing referred as adventitious presence (AP) or low level
presence (LLP) (Codex Alimentarius Commission, 2003; Demeke et al., 2006; Brookes, 2008;
McCammon, 2010). The former refers to the case of non-transgenic seed mixed with transgenic
seed of an event with regulatory approval. The later refer to the case of imported transgenic or
non-transgenic seed mixed with transgenic seed of an event that has not received regulatory
approval in the importing country.
Finally, gene flow could also result from horizontal gene transfer between unrelated
organisms. Although this manner of gene flow has been raised as a concern (Snow et al.,
2005), it will not be discussed in this thesis due to its extremely low probability of occurrence
(Nielsen et al., 1998; Syvanen, 1999, 2012; Kees, 2008).

Secondary unexpected effects
Intended effects are those expected to occur according to the gene introduced, for
example insect or virus resistance, herbicide tolerance or intended alterations in the grain
composition. Intended effects are quantified in efficacy tests to verify that the introduced
gene is expressing the desired phenotype which gives an advantage compared with the
conventional counterpart (Raybould et al., 2010). Intended effects are also measured by
21

comparative analysis of phenotypic parameters and plant organ composition with the
conventional counterpart (EFSA, 2006, 2011). Phenotypic measures include agronomic
performance parameters, yield, disease resistance, or others defined according to the trait
introduced and mechanism of gene action. In the case of alteration in composition, target
compounds such as newly expressed proteins, macro- and/or micro-nutrients are quantified
(EFSA, 2006).
Unintended effects refer to consistent differences in phenotype and/or plant
composition between the GE plant and the corresponding control plants other than the
intended effects of the introduced trait (EFSA, 2006). Possible sources of unintended or
unanticipated effects include:
a) An effect of the insertion site of the transformation event.
b) An indirect effect of the introduced gene or its protein.
The first case includes transformation-induced-mutations that could occur due to the
transgene insertion into the plant genome interrupting other gene expression. According to
Wilson et al (2006) transformation-induced-mutations can be classified as: changes
associated with disruption of the plant genomic DNA caused by the site of insertion; the
presence of non-genomic DNA such as DNA sequences from the vector used; and any
alteration to the plant genomic DNA, including: base pair changes, duplications, deletions or
rearrangements as well as somaclonal variation. These alterations can be caused by the
mechanism used to insert the transgene into the plant (mainly Agrobacterium-mediated
transformation or particle bombardment), or during the plant regeneration process that
includes tissue culture.
The other source of unintended effects refers to the unintended phenotypes that the
trait and gene itself potentially could cause (Wilson et al., 2006). This source of unintended
effects is linked to perturbations due to interactions within plant metabolic, signalling or

22

regulatory pathways and may be more likely with some of the new genes and traits under
development (Wolfenbarger and Grumet, 2002; Little et al., 2009).
The unexpected effects are not harm ‘per se’. Rather, specific harms, as discussed in
previous sections, are considered regardless of whether they occur due to a direct effect of the
gene product or to unexpected secondary effects (Personal Communication, Sally L.
McCammon, Ph.D., Science Advisor, Office of Science Biotechnology Regulatory Services,
Animal and Plant Health Inspection Service APHIS-USDA, 2010).
The detection of unexpected effects begins at early stages of the GE crop development
during the regular evaluation of risks. The criterion used is the concept that traditionally
cultivated crops have a history of safe use regarding food/feed safety and environmental
security. This is the criteria of ‘familiarity’ generally used in biosafety frameworks. The
evaluation of risks is based on a comparative assessment in which the GE plant is compared
with its non-GE conventional counterpart. If only intended differences are identified, it is
considered that the GE plant is substantially equivalent to its counterpart and no further data
in necessary. If unintended differences are identified, it is determined whether the difference
is biologically relevant and the probability that this difference will determine an
environmentally harmful effect (Garcia-Alonso, 2010). If the difference has biological
relevance, further analyses are performed focusing on that factor. The analyses performed are
the same as if intended or unintended effects were causing the difference. If pre-commercial
release field trials show that the transgenic line being tested exhibits unexpected negative
agronomic or potential environmental negative effects, that construct, or that event, if it is an
insertion effect, would be dropped from further development.
On the other hand, there may be cases where unintended effects are not identified
during the comparative assessment stage. It is of concern that such changes may be manifest
when the crop is commercially released in large areas. Thus, regulatory systems may request

23

the applicant to assess the probability of occurrence of unintended effects. This is a challenge
for the regulatory authority, since it is unclear what would be the appropriate requirement to
the applicant in order to assess the probability of unintended, unidentified effects. The
Brazilian and European Union’s biosafety frameworks include the consideration of
unexpected, unidentified effects by requesting a monitoring plan after the GE crop is
authorized for commercial release (BRAZIL, 2011; EFSA, 2006).

Changes in agricultural practices
The gene introduced may confer a trait that determines changes in agricultural
practices, usually referred as “associated technology”. This is the case for traits such as
herbicide tolerance. A commercial release of an herbicide tolerant crop may determine the
increase usage of the herbicide for which the trait gives tolerance. An increase in the usage of
a particular herbicide may require an adjustment in the analysis of the negative impact on
non-target organisms and may require measures to prevent the generation of herbicide
resistance because of its increased use (Ríos et al., 2005; Cerdeira and Duke, 2006; Young,
2006; Cerdeira et al., 2011).
The use of herbicide tolerance also has influenced tillage practices by allowing
reduced or no tillage production. It is also possible that the new crop/trait could favor
agricultural expansion into natural environments not currently under cultivation, such as areas
currently limited by drought or salinity. The implications of the changes in agricultural
practices can be considered in the context of the risk assessment process done by the
biosafety framework or can be considered by other environmental agencies.

24

GENETICALLY ENGINEERED CROPS AND A BIOSAFETY FRAMEWORK
Why regulate genetically engineered crops?
Biosafety in its broad sense refers to “a) the goal of ensuring that the development
and use of genetically engineered organisms and products made from them do not negatively
affect plant, animal, or human health; genetic resources; or the environment; b) policies and
procedures adopted to avoid risk to human health and safety, and to the conservation of the
environment, as a result of the use of genetically engineered organisms for research and
commerce”(Traynor et al., 2002). “Biosafety” is a global concept advisable for a sustainable
agricultural development due to its integrated approach. It encompasses not only the
introduction and release into the environment of genetically engineered organisms and their
products, but also food security, zoonosis, introduction of pests and diseases of animals and
plants, and introduction and management of invasive alien species (FAO, 2007). Thus, GE
organisms are one aspect of the concept of biosafety. This section describes the regulation of
the release of GE organisms.
Specifically regarding GE organisms, the Convention on Biological Diversity
defines biosafety as the “means to regulate, manage or control the risks associated with the
use and release of living modified organisms (LMOs) resulting from biotechnology which are
likely to have adverse environmental impacts that could affect the conservation and
sustainable use of biological diversity, taking also into account the risks to human health”
(UNEP/CBD 1992, Article 8(g)). As part of the CBD, it is The Cartagena Protocol (CP) on
Biosafety (2000) that is an international treaty that regulates living modified organisms
(LMOs) resulting from “modern biotechnology”. The CP refers to LMOs as “any living
organism that possesses a novel combination of genetic material obtained through the use of
modern biotechnology” and defines “modern biotechnology” as the application of:

25

a. In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA)
and direct injection of nucleic acid into cells or organelles, or
b. Fusion of cells beyond the taxonomic family that overcome natural physiological
reproductive or recombination barriers and that are not techniques used in
traditional breeding and selection”
For the Cartagena Protocol the concept of biosafety refers to “the need to protect human
health and the environment from the possible adverse effects of the products of modern
biotechnology” (Secretariat of the Convention on Biological Diversity, 2000).
Genetic engineering technology, also called recombinant DNA technology, has the
potential to generate a broad range of new products, including organisms with significantly
altered morphology and physiology. Both the process of genetic engineering and the potential
impact of the resultant products have led to a cautious attitude. As a result, unlike
conventionally bred cultivars, products obtained through the process of genetically
engineered are subject to regulation.
The concern regarding GE organisms rose at the beginning of their development from
U.S. scientists who were working with recombinant DNA. The Asilomar Conference in
February 1975 reviewed the progress in this technique and discussed potential biohazards of
working with this methodology (Berg et al., 1975). Scientists recognized the potential of this
technology for molecular biology and for future (at that time) useful practical applications.
The organizing Committee tried to reach a consensus in the appropriate way to deal with the
potential risks in laboratory work with recombinant DNA. Recommendations arose with
different levels of containment according to the type of experiment (Berg et al., 1975).
The following year the US National Institute of Health (NIH) published the guidelines
for research that uses recombinant DNA (NIH, 1976, 1978). Since then until 1984, the NIH
Recombinant DNA Advisory Committee was the federal entity charged with reviewing and

26

monitoring DNA research in the US. Progress of this technology in parallel with growth of
biotechnology companies and legal issues associated with intellectual property rights led the
US government in 1984 to consider and establish policies to guide federal agencies in the
regulation of biotechnology research and its products. In 1984 the White House Office of
Science and Technology Policy (OSTP) published the “Coordinated Framework for
Regulation of Biotechnology” which was finalized in 1986.

How to regulate genetically engineered crops?
Various challenges are presented when implementing a regulatory system for
genetically engineered organisms. Human, financial and infrastructure resources are required
for an operational biosafety framework. The objective is to develop a regulatory system that
is: responsible, appropriate, clear, transparent, consistent, predictable and cost/time-effective
(UNEP, 2005). In order to obtain confidence and credibility in the regulatory system it is
necessary to have a clear state policy supporting the technology while recognizing the need
for regulation. The final regulatory system will depend on each country’s own legal system,
form of government, obligations, objectives and priorities (UNEP, 2005). Several papers
have described and compared regulatory systems of different countries (Flint et al., 2000;
MacKenzie, 2000; Solleiro and Galvez, 2002; McLean et al., 2003; Nap et al., 2003; Jaffe,
2004; McHughen and Smyth, 2008; Ramessar et al., 2009; Hokanson and Ferenczi, 2011).
The necessary components of a national biosafety framework include: 1) a national
biosafety policy; 2) a regulatory regime comprised of laws, acts, decrees and other legal
instruments; 3) an administrative system to deal with applications in which the competent
authority/ies will carry forward the decision-making procedure (risk analysis); 4) follow-up
actions (inspection, enforcement, emergency provisions, etc); and 5) public awareness and
participation (UNEP, 2005; García-Huidobro, 2011). These components, and decisions and
27

considerations required in designing them, have been extensively described in numerous
reviews (Traynor et al., 2002; UNEP, 2005; FAO, 2007). Some of the key decisions and
considerations are discussed below. Table 1.4 summarizes the elements necessary for the
implementation of the decision-making procedure.

Table 1.4. Elements necessary for the implementation of the decision-making procedure
(modified from UNEP, 2005).
Element
Objective

Scope
Principles
Institutions
Administrative
system
Decisionmaking
procedure
Monitoring
Control
Labeling
Liability and
redress

Notes
To identify what is to be protected and the level of
protection to be sought. This refers to the protection of the
health and environment being possible to include other
objectives such as socioeconomic considerations,
coexistence, etc.
To define the products/organisms and activities to be
regulated.
To define basic principles that will underlie the decisionmaking procedure.
To define responsible institutions for the implementation of
the regulatory system.
To define an administrative system that will deal with
applications.
To define the methodology for the decision-making
procedure.
To define if the framework would provide for monitoring of
the effects of an authorized GE crop/product post-releases.
To define what inspections and enforcement actions would
be required and what institution would undertake them.
To define if there would be specific label requirements.
To define whether the framework will have a specific
provisions on liability and redress
Source: Modified from UNEP, 2005.

When defining the regulatory regime (laws, decrees, etc), the biosafety framework can
be developed using existing laws as it is the case for the US and Canadian systems, where
already existing laws were considered sufficient to regulate GE organisms. The decision to
regulate under existing laws also implies that the regulatory needs for biotechnology are not
different from other types of regulated articles (Hokanson and Ferenczi, 2011). On the other
hand, specific regulation for GE organisms can be written, as it is the case in the European
28

Union (EU), or a mix of already existing laws and decrees may be combined with new
regulation written specifically for GE organisms as has been done in several countries from
South America and Africa. Each approach has its advantages and disadvantages.
If using existing laws, agencies involved and general configuration of the system are
already established. However the specific commitments of an institution must also be linked
with the regulation of GE organisms. In the US for example the USDA/APHIS regulates
insect and herbicide tolerant GE crops as ‘plant pests’ because that is within its purview. The
US EPA regulates only ‘plant incorporated protectants’, such as gene products of Bt crop
plants, because it regulates traditional insecticides in agriculture (Hokanson and Ferenczi,
2011).
Another approach is the one taken by New Zealand that includes the regulation of GE
organisms under the wide concept of biosafety (FAO, 2007). New Zealand includes GE
organisms as “new organisms” under the Hazardous Substances and New Organisms Act
(HSNO Act) (NEW ZELAND, 1996) in coordination with their Biosecurity Act (NEW
ZELAND, 1993). Thus, New Zealand does not have a specific Act or Law for GE organisms.
Regarding the decision-making procedure, the criteria that will trigger the regulatory
process could be process-based or product-based. The majority of countries that have in
place a biosafety framework use the process-based criteria. Any organism derived from
genetic engineering is considered a regulated product and needs to go through the regulatory
process. This is the criterion established by the Cartagena Protocol. Any living organism
generated through the process of genetic engineering needs to comply with the regulatory
requirements even if the same product, for example a drought tolerant corn variety, obtained
by conventional breeding techniques, already has been released into the environment. Canada
on the other hand has a clear product-based regulatory system in which it is not the process
that triggers the regulatory system, but the final product, regardless of the process to obtain it.

29

In Canada release into the environment of all new genetic combinations that determine a
novel trait are regulated. Novel traits in Canada are defined as a trait which is both new to the
Canadian environment and has the potential to affect the specific use and safety of the plant
with respect to the environment and human health (Canada - CFIA, 2013). Thus, not only
new products derived from genetic engineering but also through mutagenesis or other
“conventional” methods are regulated (Nap et al., 2003; CERA website, 2013). This
approach considers that there are methodologies in conventional breeding with the same
potential risks as those posed by recombinant DNA (NAS, 2002).

Specialty crops regulatory challenges
Incorporating biotechnology and molecular plant breeding into national plans requires
intellectual and infrastructure capacity, as well as financial resources for the regulatory
system. The limited budget and low institutional support for the specialty crops sector has
limited ability of this sector to proceed through the expensive regulatory system needed to
reach the commercial phase of developed biotech crops (US Pew Initiative on Food and
Biotechnology, 2007). Even though these crops may be attractive for commercial companies,
depending on the country’s market, the cost of discovery, development and authorization for
commercial release of a transgenic event is estimated in US$ 135 million (James, 2012), of
which between US$ 7 and US$ 10 million correspond to the regulatory approval process
(Kalaitzandonakes et al., 2007). Regulatory costs vary by country, crop and trait and depend
whether the GE crop is developed by a public institution, such is the case of China, or private
company such as in US and India (Bayer et al., 2010). Bayer et al., (2010) found the cost of
regulatory compliance to be between US$ 3 and 12,5 million in the US, US$ 195,000 in India
and between US$ 53,000 and 90,000 in China.

30

The same regulatory system is applied for all situations despite the great diversity
among specialty crops and the variety of target traits. The fact that the regulation is required
event-by-event may not be as much of a limitation for commodity crops such as corn in
which after an event has been approved, other varieties of the same crop with the same event
can be generated by cross-breeding and these new events do not need to go through the
regulatory system. However, in the case of some specialty crops, such as those that are
clonally reproduced, each variety needs to be genetic engineered for the trait to be
incorporated and then each event needs to go through the regulatory system. In addition, new
varieties of specialty crops are generally in the market for a short time before being replaced
(Fernandez and McCammon, 2007), further necessitating an expedited system of regulation.
This situation has inspired the Pew Initiative on Food and Biotechnology and the US
Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) who
co-sponsored a workshop entitled “Emerging Challenges for Biotech Specialty Crops” (US
Pew Initiative on Food and Biotechnology, 2007) to examine the problems that engineered
specialty crops encounter with the regulatory system). This workshop was the last of several
workshops organized by the Pew Initiative and sponsored by different US governmental
agencies to understand particular issues of specialty crops regulation (Pew Initiative on Food
and Biotechnology, 2007; Personal Communication Sally L. McCammon, Ph.D., Science
Advisor, Office of Science Biotechnology Regulatory Services, Animal and Plant Health
Inspection Service APHIS-USDA, 2010, 2013). Government regulators, scientific experts,
industry representatives and policy makers from the biotech specialty crops sector had
roundtable discussions to identify the challenges and to find possible solutions to improve the
regulatory system to making it better adapted to the biotech specialty crops sector.
Table 1.5 lists six proposals reached at a workshop held in 2007 (Fernandez and
McCammon, 2007). One suggestion to improve the regulatory system for specialty crops was

31

development of a tiered risk-based regulatory system (proposal 1 in Table 1.5). Three critical
pieces of information were suggested as the basis for regulatory decisions: the geographical
range of compatible relatives; the invasiveness/weediness of the crop and its relatives; and
the phenotype of the transgene. It was stressed that the critical parameter should be the
plant’s new phenotype conferred by the transgene. In this way, the lower-tier biotech crops
(i.e., no compatible relatives, non-weedy or invasive, new phenotype not likely to cause
environmental consequences) would require less data and information while the higher-tier
products would require more information to collect.
Another suggestion to adjust the regulatory system for these crops is to switch from
the case-by case approach to consider categories of crop-trait-environment (proposal 2 in
Table 1.5). The effect of a particular trait on a set of orphan crops with common genetic
structures, at a similar limited production environment can be analyzed together.
The necessity to develop information modules (and white papers) that can be used in
the application process to accelerate the writing and evaluation of new submissions was also
discussed (proposal 3 in Table 1.5). The idea was to generate a database publicly available
with the existing scientific data relevant for risk assessment. Different modules can be created
focusing on different areas of biotechnology. One module will cover all the relevant
information for environmental risk assessment (e.g. wild relatives and geographic
distribution, invasive/weeds characteristics) for each of the specialty crops. Another module
will focus on the basic tools and methods used in genetic engineering (e.g. promoters,
terminators, marker genes, transformation technologies). The information of these modules
will help to guide the tiered risk-based suggested regulatory system.

32

Table 1.5. Proposals of the Pew Initiative on Food and Biotechnology Workshop, 2007.
Updated by personal communication with Sally L. McCammon, Ph.D., Science Advisor,
Office of Science Biotechnology Regulatory Services, Animal and Plant Health Inspection
Service APHIS-USDA, 2010, 2013.
Workshop’s
proposal
Develop a
tiered, risk1 based
regulatory
system

2

3

4

5

6

Update of activities

APHIS developed one such system in proposed revisions of its
biotechnology regulations, published in 2008
(http://www.aphis.usda.gov/brs/fedregister/BRS_20081009.pdf).
The proposed revisions are still under internal discussion after
receiving public comment on the proposed regulatory changes.
APHIS is currently participating in the development of a project
Move away
with Canada and Mexico to look at the topics related to
from eventretransformation as part of evaluating recent scientific
by-event
advancements and analysis for their implications in regulatory
regulation
assessment.
Develop
APHIS continues to participate in the development of Organization
information
for Economic Cooperation and Development (OECD) plant biology
modules and documents and other OECD biotechnology documents
white papers (http://www.oecd.org/department/0,3355,en_2649_34385_1_1_1_1
for use in
_1,00.html). In addition, APHIS works with the scientific
applications
community to address regulatory questions through such avenues
for regulatory as the Biotechnology Risk Assessment Grants (BRARG) program
clearance.
and the Association of Official Seed Certifying Agencies (AOSCA).
Increase transparency and condense the timeline. APHIS is
actively working to increase transparency and to streamline its
review processes. In August, 2010 APHIS published updated
guidance on notification process for field testing
Increase
(http://www.aphis.usda.gov/biotechnology/notifications.shtml). In
transparency
November, 2011 APHIS announced petition process improvements.
and condense
After receiving comment, the plan for implementation was
the timeline
published in March, 2012. In May, 2012, APHIS provided and
updated permit User’s Guide
(http://www.aphis.usda.gov/biotechnology/brs_main.shtml,
USDA,APHIS-BRS 2012).
Prepare for
new types of APHIS continues to actively assess technological developments in
products and biotechnology for implications to its regulatory system.
technologies
APHIS attempted to address some legal concerns with its proposed
Legal
revision of the biotechnology regulations published in 2008 (link in
concerns
item 1).

33

One product of the Pew Initiative was the formation of the Specialty Crops
Regulatory Assistance (SCRA) initiative (SCRA website, 2013). It is a public-private effort
to assist developers from the public and private sector that work with specialty crops to
complete the US regulatory process to achieve commercialization. SCRA was inspired by
other public-private partnerships such as the IR4 pesticide management project to facilitate
the registration with regulators of pesticides for minor uses (IR4 website, 2013) and the Food
and Drug Administration (FDA) orphan drug approach (Office of Orphan Product
Development OOPD-FDA website, 2013) (Personal Communication, Sally L. McCammon,
2010). The last workshop was in December 2011 entitled ‘Nuts and Bolts of US Regulatory
Dossiers for Genetically engineered Crops’ (SCRA, 2013). In this workshop different case
studies were presented as examples of specialty crops already developed, such as plum with
virus resistance to plum pox, or in the process of commercial approval, such as peanut
resistant to Sclerotinia Blight and Bt Potato resistant to potato tuber moth.

RISK ANALYSIS METHODOLOGY
Risk analysis is defined as a process for controlling situations where populations or
ecological systems could be exposed to a hazard (EC, 2000). Risk analysis arises as a
methodology to characterize, manage and communicate the risk by public policy decisionmakers. The application of a formal risk analysis methodology has become routine in many
activities including the use of chemical, biological and physical agents, industrial and general
processes. Existing International Standard Guidelines refer to biological and environmental
risk analysis (EC, 2002; International Organization for Standardization, 2005), as well as in
other disciplines such as business, management and insurance (Hill and Sendashonga, 2003;
International Organization for Standardization, 2009).

34

A measure against possible or perceived threats is something intuitive in routinely
human activities considering mainly past experience, technical know-how and qualitative
estimates of risk (EC, 2000). However, nowadays decisions of modern society increasingly
require guarantees regarding food safety and environmental sustainability (Power and
McCarty, 1998). Risk Analysis is a useful methodology to approach the scientific assessment.
Additional factors such as societal, economic, ethic and political values may also be included
in the decision-making process (EC, 2000). Governments have relied on Risk Analysis as a
guideline for a decision making to be as objective as possible with regard to new
technologies and processes including GE crops (US NRC, 1983, 1996; EC, 2002). General
frameworks proposed for risk analysis and its components of other activities have been
adjusted to agriculture biotechnology (Wolt and Peterson, 2000). Risk Analysis is the
internationally accepted methodology that countries apply for the decision making process to
determine whether or not to accept the introduction and use of GE organisms (OECD, 1993,
1995; US NRC, 1996; Secretariat of the Convention on Biological Diversity, 2000; Codex
Alimentarius Commission, 2003; EC, 2002a,b).
Risk is the possibility of an unwanted harm to occur. Risk is defined in terms of
likelihood of occurrence of the undesired harm as a measurable probability (Wolt and
Peterson, 2000). Assessment of risk is a science-driven process in which probability of risk is
quantitatively determined. However the product of the Risk Analysis process is a judgement
of an acceptable risk, which corresponds with the concept of safety (Lowrance, 1976 cited in
Wolt and Peterson, 2000). In the judgement of an acceptable risk other factors of public
policy decision-making such as societal, economic, legal, ethic, cultural and political factors
also are considered (Wolt and Peterson, 2000). Thus, the Risk Analysis methodology
considers science and the other factors necessary for the judgement of an acceptable risk
resulting in a process consisting of three interconnected components: risk assessment, risk

35

management and risk communication (Codex Alimentarius Commission, 2003; International
Organization for Standardization, 2009).
Risk assessment follows a science-based methodology. Risk management considers
the risk assessment results but includes other factors necessary for a public policy decisionmaking (societal, economic, ethic, legal, political). Risk communication has the objective that
the risk analysis process deals transparently with scientific, social, cultural, economic and
political issues for an effective final decision regarding the new technology risk (Wolt and
Peterson, 2000). While risk analysis methodology is currently widely used internationally in
decision-making as to whether or not to authorize the release of a GE organism, the risk
analysis components could vary significantly among countries regarding legislation,
administrative procedures and assessment protocols. Below follows a brief history of risk
analysis in the international context and the description of its components adjusted to
genetically engineered organisms.
The first formal guideline of risk analysis published in the United States by the
National Research Council (NRC), contained the basis for risk assessment of human health in
the so-called “Red Book” (US NRC, 1983). The ‘Red Book’ contains a general approach
outline for the characterization of adverse effects on human health due to exposure to hazards
from human activity. It recommends basing the framework on a science-driven risk
assessment process to provide information to risk managers about human health (NRC,
1983). At the same time risk analysis was emerging as a formalized discipline and tool for
policy decision-making (Wolt and Peterson, 2000) as reflected in international standards for
risk analysis (OECD, 1986, 1993, FAO/WHO, 1995). Table 1.6 lists initial comprehensive
guidelines published for risk analysis and/or its components.

36

Table 1.6. Guideline documents about risk analysis and/or its components, modified from
Hill and Sendashonga (2003).
Year

Document

1983

Red Book

1986

Blue Book

1989

1993
1996

Framework on
human health and
ecological risk
assessment
Updated of the Blue
Book.
Orange Book
Framework for
Ecological Risk
Assessment

1996

1998

1999

Technical guidance
document on risk
assessment for
existing and new
substances.
Guideline for
Ecological Risk
Assessment
Guidance on
principles for risk
assessment
and monitoring for
the release of
genetically modified
organisms.

Description
Risk analysis framework on human health safety
elaborated by the National Research Council
(NRC), USA.
Recombinant DNA Safety Considerations
elaborated by the Organization for Economic Cooperation and Development (OECD).
Integrated framework on human health (Red Book)
and ecological risk assessment, elaborated by the
Committee on Risk Assessment Methodology
(CRAM) convened by NRC, USA.
Updated of the Blue Book (OECD)
Updated and expanded version of the Red Book
(NRC)
Framework for Ecological Risk Assessment
elaborated by the Canadian Council of Ministers of
the Environment (CCME) for application to
contaminated sites.
Technical guidance documents in support of the
Commission Directive 93/67/EEC on risk
assessment for new substances
and the Commission Regulation No. 1488/94 on
risk
assessment for existing substances elaborated by the
Commission of the European Communities (CEC),
Brussels, Belgium
Guideline for Ecological Risk Assessment
elaborated by the Environmental Protection Agency
(EPA), USA.
Guidance document of risk assessment elaborated
by the Department of the Environment, Transport
and
Regions (DETR), London, UK

According to Barnthouse (1994), a Committee on Risk Assessment Methodology
(CRAM) was convened by the NRC in 1989 to develop a conceptual framework, based on
the ‘Red Book’, integrating human health with ecological risk assessment. The integrated
framework reaffirmed the recommendation of the ‘Red Book’ that risk assessment and risk
37

management must be two separated phases but working together and included as four basic
steps: Hazard identification, Exposure assessment, Exposure-response assessment, and Risk
characterization. The CRAM guideline lists other recommendations including implementing
a follow-up of the risk assessment with basic research and monitoring to verify accuracy of
predictions and reduce uncertainties for future risk assessments.
In that time frame the US Environmental Protection Agency (EPA) published a
guideline for ecological risk assessment of chemical substances (US EPA, 1998). The EPA
guideline was based on the criteria established in the Red Book (NRC, 1983) and follows the
methodology recommended by CRAM (Barnthouse, 1994). This EPA guideline introduces
the approach of ‘Problem Formulation’ as a ‘systematic planning step’ equivalent to the
CRAM’s first step of ‘Hazard identification’ (Barnthouse, 1994, US EPA, 1998).
The Organization for Economic Co-operation and Development (OECD) convened a
Group of National Experts on Safety in Biotechnology that developed several guidance
documents for GE organisms with a first document called the ‘Blue Book’ (OECD, 1986)
containing safety considerations for working with recombinant DNA (Table 1.6). Since 1988
this OECD Group updated the Blue Book further developing scientifically sound principles
for safety and practices for the application of GE organisms compiled on a guidance
document published in 1993 (OECD, 1993). The general safety principles included in the
OECD (1993) document were the identification of hazards, application of risk assessment for
the determination of the likelihood and consequences of hazards, and risk management. This
document also includes the criterion of the principle of familiarity used today (explained later
in this chapter). It also considers the environmental safety of scale-up of GE plants which is a
follow-up of the work “Good Development Principles (GDP): Guidance for the Design of
Small-Scale Research with Genetically Modified Plants and Microorganisms” (OECD,
1993).

38

Risk Analysis is based on science but also requires dealing with probability and
uncertainties. This explains the components of the risk analysis clearly separating the risk
assessment phase where a strict science-based analysis is performed, from the risk
management phase which its members assume a risk level and associated uncertainties.
However, since the first frameworks in risk analysis (NRC, 1983; OECD, 1986), frameworks
have evolved giving a greater involvement to stakeholders and higher social participation
during the different process phases. The framework described in the ‘Red Book’ evolved to a
framework that includes other policy considerations such as the societal, economic, ethic,
legal, political considerations reflected in the ‘Orange Book” (NRC, 1996). Thus, although
frameworks maintain an important role for science, and the role assigned to science in risk
assessment is the most agreed criterion among the existing frameworks, risk assessment is
integrated with risk management and the risk analysis process is defined as an iterative cycle
that links assessment with management (Power and McCarty, 1998; Hill and Sendashonga,
2003).

Risk assessment
Risk assessment is defined as the process of evaluation, including the identification of
uncertainties, of the likelihood and severity of an adverse effect (s) /event(s) occurring to man
or the environment following exposure under defined conditions to a risk source(s) (EC,
2000). The risk assessment phase follows a sequence of steps based on scientific criteria to
predict possible harms (adverse effects) that may arise, in the case of GE technology as a
consequence of hazards (risk sources) introduced by the GE crop phenotype (US NRC, 1983,
1996; US EPA, 1998; EC, 2000, 2001,2002). Another definition refers to risk assessment as
a process intended to calculate or estimate the risk for a given target system following
exposure to a particular substance, taking into account the inherent characteristics of a
39

substance of concern as well as the characteristics of the specific target system (EC, 2000).
Hazards that could cause adverse effects on biosafety, including food and environmental
safety, are evaluated. This thesis focuses on the risk assessment methodology for
environmental issues. Socioeconomic aspects may also be included with a science-based
methodology, but strictly speaking, biosafety covers human/animal health and environmental
security.
One of the criteria applied to determine potential adverse effects of transgenic crops
on the environment is to perform the risk assessment process on a case-by-case basis based
on the trait, crop, and the receiving environment (Figure 1.1) (Snow and Palma, 1997;
Grumet and Gifford, 1998; FAO/WHO, 1996, 2000; Secretariat of the Convention on
Biological Diversity, 2000; Dale et al., 2002; Conner et al., 2003, Nap et al., 2003; Grumet et
al., 2011). Another criterion is the concept of familiarity (OECD, 1993; Codex Alimentarius,
2003). The concept of familiarity considers whether the GM phenotype is novel for the
ecosystem under study (NRC, 1989). It is based on a comparative risk assessment approach
in which the GE plant is compared with the corresponding non-GE. The non GE-plant refers
to the parent line or non-transformed near isogenic lines from which the transgenic crop
derives, and other plant varieties developed by conventional breeding present already in the
market with a history of safe use plant (Kuiper et al., 2002; Conner et al., 2003; EFSA, 2006,
2010, 2011). The commercial varieties that are generated by conventional breeding without
being through rigorous laboratory tests before being marketed, have been consumed for
decades and they have gained a history of safe use (Kok and Kuiper, 2003). This approach
has been further elaborated by the OECD and formalized in the so-called Principle of
Substantial Equivalence (OEDC, 1993).
Plants developed by traditional plant breeding are considered an integral and accepted
part of agriculture (Conner et al., 2003; Nap et al., 2003). Which comparators are considered

40

acceptable for risk assessment has been recently adjusted by the European Union regulatory
system (EFSA, 2011). The comparative safety assessment comprises a detailed analysis of
the chemical composition of the GE plant and a detailed agronomic evaluation under field
conditions performed to establish the substantial equivalence of the transgenic plant with the
familiar nontransgenic conventional crop. Field trials are performed in multi-location field
trials for several years. If no differences as a consequence of the transformation process are
identified, the risk assessment analysis continues only focusing on the trait introduced
following a step-wise (tiered) approach, with increased assessment complexity based on the
knowledge gained in each specific step (US EPA, 1998; EFSA, 2010, 2011).
The initial framework proposed in the US by the National Academy of SciencesNational Research Council (NRC, 1983) in the ‘Red Book’, established four steps for risk
assessment: 1) hazard identification, 2) hazard characterization, 3) exposure assessment, and
4) risk characterization (NRC, 1983). These steps have evolved and the risk assessment
methodology established by Codex and Cartagena Protocol follows a sequence of six steps
performed case by case for each GE crop-gene-trait-environment combination (Secretariat of
the Convention on Biological Diversity, 2000; Codex Alimentarius Commission, 2003), as
described below. In brief, risk assessment tries to answer the following three questions for
each individual case: 1) ‘What can go wrong?; 2) ‘How likely is that to happen?’; and 3)
What are the consequences if it happens? (Conner et al., 2003). Independent of the number of
steps and the terminology used to described the process, risk assessment frameworks for GE
organisms share the following criteria: it begins with Problem Formulation approach for the
identification and formulation of the problem; it is performed by an overall characterization
of risks taking into account, the probability of an adverse effect to occur, and the
consequence of those effects (Hill and Sendashonga, 2003).

41

The steps included by the Cartagena Protocol and the Codex Alimentarius (Secretariat
of the Convention on Biological Diversity, 2000; Codex Alimentarius Commission, 2003) are
the following:
1) Identification of potential hazards associated with the GE plant that would cause harm
to the receiving environment. This will depend on the specific combination of cropgene-trait and receiving environment.
2) Estimation of the probability of occurrence of the identified adverse effects, which is
related to the exposure level.
3) Evaluation of the consequences (impact assessment) if those adverse effects occur, i.e.
‘what are the consequences if it happens?
4) Characterization of the risk combining the probability of occurrence (2) by its
consequences (3). Risk = probability X consequences.
5) Consideration of possible adequate strategies for the management of the risk
characterized, which could reduce the probability of occurrence and/or its
consequences and to meet contingencies.
6) Requesting further information, or implementing risk management strategies, and/or
implementing a monitoring plan to manage uncertainty regarding the level of risk.
The term hazard refers to an inherent property of an agent or situation capable of
having adverse effects on something. Hazard can also be defined as the potential of a risk
source to cause an adverse effect (s)/event(s) understanding risk source as an agent, medium,
commercial/industrial process, procedure or site with the potential to cause an adverse
effect(s)/event(s) (EC, 2000). In the terminology used in Problem Formulation, hazard is
referred as plant attribute with the possibility of causing harm. Table 1.7 lists terminology
that is considered synonymous in the context of this thesis. Hazard is something that could
cause harm, term that is defined below.

42

Table 1.7. Terminology used in the literature for risk analysis considered synonymous in the
context of this thesis.
Risk terminology

Synonymous
Risk scenario

Hazard
Plant attribute
Harm

Adverse effect

Exposure pathway

Risk scenario

Environmental values

Environmental entities

The term harm refers to a negative outcome or effect of an action or event, used as
synonymous of adverse effect (Wolt et al., 2010). Thus, harm refers to the negative outcome
of the hazard defined above.
Risk refers to the probability and severity of an adverse effect (=harm) /event
occurring to man or the environment following exposure, under defined conditions, to
hazard(s) (= risk source(s)) (EU, 2000). It is also defined as the probability of adverse effects
(=harms) caused under specified circumstances by an agent in an organism, a population or
an ecological system (EU, 2000). Risk characterization is one of the main products of the risk
assessment process used by the risk management phase to analyze whether the risk level and
uncertainty associated with its estimation, is acceptable to take a regulatory decision
(Raybould, 2006).
Risk characterization is defined as the quantitative or semi-quantitative estimate,
including attendant uncertainties, of the probability of occurrence and severity of adverse
effect(s)/event(s) in a given population under defined exposure conditions (EC, 2000;
Secretariat of the Convention on Biological Diversity, 2000; Codex Alimentarius
Commission, 2003). Risk characterization is also referred as the integration of evidence,
reasoning and conclusions collected in hazard identification, dose-response assessment and
43

exposure assessment and the estimation of the probability, including attendant uncertainties,
of occurrence of an adverse effect if an agent is administered, taken or absorbed by a
particular organism or population (EC, 2000).
In the first step of environmental risk assessment available information regarding the
crop, gene, trait and the receiving environment is analyzed to identify potential hazards
associated with the GE plant that could cause harm to the receiving environment. The hazard
identification is the first stage of risk assessment consisting in the determination of a
particular hazard(s) (risk source(s)) capable of causing adverse effect(s)/event(s) to humans
or the environment species of a target system exposed to the hazard(s). Hazard identification
is complemented with a hazard characterization that refers to a qualitative description and,
whenever possible, quantitative or semi-quantitative evaluation of the nature of the hazard
and the effect(s)/event(s) (EC, 2000). Hazard characterization could be considered in other
risk assessment frameworks as a second step (NRC, 1983; EC, 2000). Hazard
characterization may include a dose-response assessment or dose-effect relationships when
the hazard is associated with a biological, chemical or physical agent, determination of
mechanisms of action involved, biological extrapolations, and identification of respective
uncertainties (EC, 2000).
Which information is requested in this step and how information is organized and
analyzed is key to properly construct risk hypothesis later in the process that justify further
analysis. The US Environmental Protection Agency proposes to begin risk assessment with
Problem Formulation (US EPA, 1998). Problem Formulation is an approach that assists in the
process of defining real and relevant risk hypothesis. The Problem Formulation approach will
be explained later in this section.
Step two of risk assessment is to estimate the probability of occurrence of harm
(Codex Alimentarius Commission, 2003; Secretariat of the Convention on Biological

44

Diversity, 2000), i.e. an adverse effect to the environment due to a hazard associated with the
GE crop. The probability of occurrence of harm will depend on the likelihood of the hazard
(=risk sources identified in step 1) to come into contact with entities that have been defined
as valuable to protect (for example wild relatives as part of biodiversity). The process by
which such contact occurs is the exposure (Wolt et al., 2010). Thus, as defined by Wolt et al.,
(2010) the exposure pathway (or scenario) “is a particular set of circumstances describing
the opportunity for harm to an environmental entity of value”. The quantitative or semiquantitative evaluation of the likely exposure of the entity of value to hazards (= risk sources)
is referred as exposure assessment (EC, 2000).
The estimation of the likelihood of occurrence of harm for a defined exposure
pathway (exposure assessment) also takes into account the level and kind of exposure that the
receiving environment will have with the GE plant (Nickson, 2008). A primary factor
influencing exposure is category of use requested (e.g., field trial vs seed multiplication vs
commercial release).
In some risk assessment frameworks exposure assessment is considered as a third step
separated from the estimation of the probability of occurrence of hazard, not harm, as just
described above (NRC, 1983; EC, 2000). In this risk assessment approach risk
characterization is the next and last step considering it as function of a defined hazard and its
likelihood of exposure (NRC, 1983). Exposure assessment may include the inference of
possible consequences that harm may have for a given population of particular concern (EC,
2000). The evaluation of possible consequences if harm occurs is considered in the next step
according to the framework established by Codex Alimentarius (Codex Alimentarius
Commission, 2003) and Cartagena Protocol (Secretariat of the Convention on Biological
Diversity, 2000).

45

Step three of risk assessment evaluates the possible consequences if harm occurs
(Secretariat of the Convention on Biological Diversity, 2000; Codex Alimentarius
Commission, 2003), i.e. the seriousness and magnitude of harmful effect when environmental
values of the receiving environment are exposed to the identified hazards of the GE plant
(Nickson, 2008; Wolt et al., 2010). Assessment of consequences also takes into account the
level and kind of exposure that the receiving environment will have with the GE plant as was
mentioned in exposure assessment that is related to the category of use requested (e.g., field
trial vs seed multiplication vs commercial release). Table 1.8 lists examples of association
between hazards, harms and possible consequences with regard to GE plants.
An example of harm to an environmental entity associated with a hazard derived from
a GE plant would be that existing wild relatives in the receiving environment (environmental
entity) become more persistent under water stress conditions (harm) due to the capacity of
dehydration stress tolerance (hazard acquired from being exposed to a GE crop) (Table 1.8).
The fact that in the receiving environment there are wild relative plants does not
necessarily indicate that the adverse effect (harm) will occur. Conversely, presence of the
transgene alone also does not guarantee that harm will occur (Raybould, 2006). In the
exposure pathway it is necessary to consider not only the existence of wild relatives in the
receiving environment, but also whether it is a cross pollinated species, the level of fertility of
infertility in such a cross, whether there are water stress conditions, and if the transgene
effectively has the capacity to change the wild relative’s phenotype in a way that will
increase its persistence. If the exposure pathway is confirmed, a consequence to assess in this
example would be the possibility of the wild relative to become an invasive species. Another
example of hazard associated with a GE crop is the expression of a protein toxic to insects
that can cause an environmental harm by decreasing the abundance of non-target beneficial
insects present in the receiving environment.

46

Table 1.8 Examples of association between hazards, harms and possible consequences with
regard to GE plants.
Hazard
Category

Harm
Example

Insect resistance

Receiving
environment

Non-biosafety
issues, for
example, a
commercial
situation

Could be toxic to
non-target insects

Drought tolerance
Gene product/
Trait conferred
by the
introduced
gene(s)

Consequence

Could increase the
persistence of the
GE crop.

Could be
introgression of the
transgene into wild
relatives. The harm
will depend on the
Drought tolerance
resulting phenotype,
for example
increased
persistence of wild
relatives.
Could be
introgression of the
Center of origin of the transgene into wild
GE crop species
relatives. The harm
will depend on the
resulting phenotype.
The fact that Uruguay
currently is exporting
to Europe exclusively
non-GE rice.

Decrease in the
population of non-target
insects changing the
ecosystem functions.
The GE crop becomes a
weed in the
agroecosystem or invades
natural areas.

Wild relatives become an
invasive species
competing with other
species affecting the
ecosystem relationships.

Could affect biodiversity
depending on the
competitiveness of the
resulting phenotype.

GE rice could affect
sales to the EU’s
The rice sector could lose
market if GE rice is one of the main markets.
found mixed.

In these examples, the probability of occurrence of harm (step 2), i.e. increased
persistence of wild relatives and decreased abundance of non-target organisms, is estimated
as function of the likelihood of risk scenarios, i.e. a wild relative is exposed to a GE crop that
confers dehydration stress tolerance; and for the second example a susceptible non-target
organism is exposed to a GE crop that expresses a protein in a level that is toxic to them. The
possible consequences in these examples would be that wild relatives become an invasive
species and a change in ecosystem relationships and function due to beneficial insects
47

decreased abundance or extinction (Table 1.8). Problem Formulation approach assists in this
step of evaluating the consequences, also by narrowing the assessment of harm magnitude to
relevant consequences that effectively can occur (Reybould, 2006; Nickson, 2008; Wolt et
al., 2010).
In step four of risk assessment the risk is characterized based on the previous steps, as
a function of the possibility of a defined harm to occur (step 2) and the consequences if the
harm happens (step 3), according to the relationship: Risk = probability of harm to occur X
consequences (Secretariat of the Convention on Biological Diversity, 2000; Codex
Alimentarius Commission, 2003). In turn the possibility of harm to occur depends on the
likelihood of a real exposure pathway between hazards of the GE plant with an environmental
value (Figure 1.3).

Figure.1.3. Schematic representation of risk estimation as a function of probability of harm X
consequences if harm happens. The probability of harm to occur depends on the hazard X
likelihood of exposure.

Sometimes risk characterization is expressed as function of a defined hazard by its
likelihood of occurrence (exposure), i.e. Risk = hazard X exposure. However, risk assessment
focuses more on the evaluation of the consequences of the harm itself rather than on
increasing the precision to determine exposure (Raybould, 2010). A more comprehensive
expression of risk characterization integrates this definition of risk (hazard X exposure),
48

referred as the probability of harm, with the magnitude of the consequences resulting in Risk
= probability of harm X consequences (Figure 1.3). In the first approach (Risk = hazard X
exposure), consequences of harm may be considered when the exposure assessment is
performed (Nickson, 2008; Wolt et al., 2010). Independently of how risk is expressed, the
important thing is not to confuse only hazard or only exposure with risk (Raybould, 2006),
and to consider the magnitude of the harm in the risk characterization. As mentioned above,
the presence of the transgene in wild relatives without causing a hazard phenotype constitutes
a situation of exposure only. In the same way, the Bt protein could be only a hazard to nontarget organisms, but to become a risk, the non-target organism has to be not only exposed to
the Bt protein, but exposed to amounts of protein that could cause harm (Sears et al., 2001).
Regarding the assessment of harm consequences, whether the increase in persistence is
limited to the area of cultivation (agroecosystem), or if it expands to natural areas and the
species become invasive, is also considered.
Assessment of consequences is related to the next steps of risk assessment, steps five
and six, which consider risk management strategies (step five) and management of
uncertainty through a monitoring plan (step six) (Secretariat of the Convention on Biological
Diversity, 2000; Codex Alimentarius Commission, 2003).
The final report of the risk assessment should inform objectively and transparently the
limitations and uncertainties found during the risk assessment process as well as if there is a
lack of scientific consensus, indicating the different scientifically justified opinions. For each
experiment performed the hypothesis tested and the results obtained should be clearly
expressed. The conclusions of the risk assessment should include the uncertainty and
variability of the data used to estimate the risk. It is not the assessor’s responsibility but the
manager’s, to determine the importance of this uncertainty in the decision making process. If

49

managers consider the uncertainty is too high, risk managers will ask for extra information or
experimental data in order to lower the uncertainty to an accepted level.
These last steps re-orient the risk assessment phase from a strictly science-based
methodology to a more risk management oriented considerations (Wolt and Peterson, 2000).
Other examples of aspects taken into account in risk assessment frameworks that show a
more expanded interconnection with risk management include: consideration of socioeconomic factors (NEW ZEALAND 1996); possible impacts of the associated technology
that may determine changes in cultivation, management and/or harvesting techniques, and not
only the impact of the event per se (EU EFSA, 2010; URUGUAY, 2011); consideration of
the agroecosystem instead of the broad ecosystem (ARGENTINA, 2003, 2011); the
feasibility of coexistence (Uruguay, 200); the acceptance of semi quantitative or qualitative
conclusions to define a regulatory decision; and the level of integration of stakeholders in the
risk assessment process (Power and McCarty, 1998).
A greater emphasis of risk management in the risk assessment phase is a request of a
sector of the civil society observed in the Uruguayan regulatory system (see chapter 2 of this
thesis). However the risk management commission that leads the risk analysis process
maintains that the risk assessment should be exclusively science-based for biosafety issues
with the exception of coexistence. The equilibrium between strictly science-based and
incorporating risk management considerations also can be considered as moving from oversimplification to over complication of ecological principles (Power and Adams, 1997).
Raybould (2006) indicates the necessity of better defining the ecological questions and the
scope of the ecological risk assessment and advocates the Problem Formulation approach to
aid in this matter. Power and McCarty (1998) indicate that a shift in the emphasis of the role
of science in the different countries frameworks is due to the differences that arise when

50

defining problem formulation steps, specifically problem context and the consideration of
stakeholders input (see later section regarding Problem Formulation approach).

Risk management
In the risk management phase the decision-making process takes into account the
results of the risk assessment and may include other considerations such as economic, politic,
legal, social and cultural factors relevant to a particular hazard in order to implement the
optimal decisions and determine appropriate actions to ensure safety (Codex Alimentarius
Commission, 2003). The final decision could be: accept the risk as it is, apply mitigation
conditions to the risk, or avoid the risk. The risk management process is distinct from risk
assessment by weighing policy alternatives according to the results of the risk assessment and
consulting with all interested parties to take into account public (EC, 2002).
In order to preserve the structure and specific function of each of the components of
the Risk Analysis methodology, the Codex Alimentarius recommends ensuring a functional
separation between assessors and managers apart from the necessary interaction between
them. This is a key issue in order to preserve the scientific integrity of the risk analysis
process, to prevent confusion regarding the function that assessors and managers should
accomplish, and to avoid any conflict of interests.
Managers should take into account the uncertainties identified in the risk assessment
process and consider the recommendations suggested by assessors to manage the risk
characterized. Managers are responsible for the implementation, surveillance, monitoring and
review of the biosafety conditions established. As in the case of the risk assessment, the
process of risk management has to be objective, transparent, coherent and completely
documented. The challenge in risk management is to find equilibrium between the best

51

biosafety conditions to minimize the risk, and the real capacity (cost and feasibility) of their
implementation.

Risk Communication
Risk communication refers to an interactive exchange of documented information and
science based opinions throughout the risk analysis process. It concerns risk-related factors
including the explanation of risk assessment findings, as well as risk perception factors and
the basis of risk management decisions (Codex Alimentarius Commission, 2003). The risk
communication process is performed among risk assessors and risk managers, with the
participation of interested groups such as the industry, the academic community, consumers,
news media and other actual or potential stakeholders as well as the general public.
The objective of the risk communication is to guarantee that all information and
necessary opinion has been considered in the decision making process for an efficient
management of the risk. Risk communication is not only the diffusion of information; it has
to do with the transparency of the whole system transferring confidence to the public
regarding the decision taken (Patton, 1998; Koch and Massey, 2011).
The risk communication process requires the implementation of mechanisms and the
use of different consultation tools that invite and promote stakeholders participation in the
decision making process (Koch and Massey, 2011). Managers choose the best mechanisms
and tools for an efficient risk communication process and have the responsibility for its
implementation.

52

PROBLEM FORMULATION
Problem Formulation has been proposed as a strategy to assist in the initial steps of
the environmental risk assessment (US EPA, 1998). According to the risk assessment steps
mentioned above, Problem Formulation provides a guideline identification of potential
hazards that could cause an environmental harm. From the point of view of regulators, the
objective of Problem Formulation is to identify real and relevant risk hypotheses that justify a
science-based risk assessment to test them (US EPA, 1998, Hill and Sendashonga, 2003;
Raybould, 2006; Nickson, 2008). It is not intended to broaden scientific knowledge in general
but to contribute to decision-making to better understand and manage uncertainty. A
coherent and logical sequence of steps is proposed to be followed in a Problem Formulation
(US EPA, 1998; Raybould, 2006; Nickson, 2008, Wolt et al., 2010). While these steps are
normally followed by regulators in some form, Problem Formulation offers a systematic
order for the steps. To reach a risk hypothesis that warrants further analysis, Problem
Formulation proposes to collect information regarding the a) Problem Context and b)
Problem Definition (Wolt et al., 2010). Table 1.9 lists the steps of the risk assessment process
(Secretariat of the Convention on Biological Diversity, 2000; Wolt et al., 2010) compared
with the steps of the Problem Formulation strategy (Wolt et al., 2010) and the scientific
method. The comparisons in Table 1.9 are adapted from Raybould (2006).
Problem Formulation begins with Problem Context and Problem Definition (US EPA,
1998). Problem Context and the majority of Problem Definition correspond with the first step
in the risk assessment approach (Table 1.9) where potential agronomic and/or ecological
risks are listed (see earlier section of this chapter about “Environmental risks for
consideration when analyzing genetically engineered crops” page 15).

53

Table 1. 9. Sequential steps of risk assessment process, problem formulation approach and
scientific method.
STEPS

RISK
ASSESSMENT

PROBLEM
FORMULATION
a) Problem Context
i. Protection goals
ii. Environmental scope
iii. Baseline information

1

2

3

Identification of
potential hazards

Estimation of the
probability of
occurrence of
potential harm
identified
Evaluation of the
consequences
identified harm
occur

SCIENTIFIC
METHOD
Collection of facts
(observations/
experimental data).
Definition of initial
problem.

b) Problem Definition
i. Plant attribute (gene
phenotype with the potential
to cause harm)
ii. Environmental value and
its measurable assessment
endpoints

Formulation of
theories and
hypotheses to explain
the facts in terms of
cause-effect.

iii. Conceptual model with
risk hypothesis

Inferences possible to
be tested from theories
and ‘null’ and
‘alternate’ hypotheses
are formulated

iv. Analysis plan

Hypotheses testing by
comparing new
observations or
experimental data with
predictions.

4

Risk
Characterization
(step 2 X step 3)

5

Consideration of
possible adequate
strategies for the
management of the
risk characterized

---

---

6

Requesting further
information, or
implementing risk
management
strategies and/or
implementing a
monitoring plan to
manage uncertainty

---

---

54

Problem Formulation strategy suggests framing the potential agronomic and/or
ecological risks according to protection goals applied to a defined environmental scope for
the assessment (US EPA, 1998; Raybould, 2006; Nickson, 2008, Wolt et al., 2010). Baseline
information and measurable assessment endpoints should be used to identify real agronomic
and/or ecological risks relevant for decision-making that are worthy of assessment.
The steps of Problem Formulation are also in agreement with the steps of the
scientific method (Table 1.9) (Raybould, 2006), with the exception that in Problem
Formulation the assessments are not always quantitative but the majority are semi
quantitative and qualitative. However it is possible to increase knowledge of risk by a cycle
of hypotheses formulation, testing, falsification and reformulation of hypotheses, as occurs in
the scientific method (Raybould, 2006, 2010; Raybould et al., 2010).
Below are explained the different steps of the Problem Formulation approach. The
process of Problem Formulation is divided into stages for explanatory purposes, but it is, in
reality, a continuum where the steps overlap.
The parameters established in the Problem Context are defined according to
protection goals and environmental scope of the country’s environmental policies together
with case-specific baseline information of the GE crop. Problem context is initiated by
analysing protection goals that are defined in the country’s law, statutes, regulations or
guidance (US EPA, 1998; Raybould, 2006; Raybould et al., 2010; Wolt, et al., 2010).
Protection goals in Uruguay for example, would be what is included in the General
Environmental Protection Law, No. 17283 of 28/11/2000, such as conservation and
sustainable use of the biological diversity and environment (air, soil, water), ecological
protected areas and avoidance of invasive alien species. According to the US legislation,
protection goals specifically for GE crops include no increased adverse effect to other
organisms, no increased weediness of the crop plant, no gene flow to sexually compatible

55

plants leading to increased weediness or altered exposure scenarios leading to adverse effects,
no increased disease and pest susceptibilities as well as no increase in adverse effects due to
changes in cultivation practices (Cordts, 2011).
Environmental scope includes several other criteria needed to determine the
parameters to be used in the risk assessment (US EPA, 1998; Wolt et al., 2010). One of the
criteria to be defined is whether environmental impacts of the event itself will be analyzed, or
whether impact of the “technology package” i.e. the associated technology will be
considered; whether the event should be analyzed in the context of the agroecosystem or
more broadly in the wild ecosystem; and whether coexistence will be considered and
regulated. The other component of Problem Context is the analysis of case-specific baseline
information used to identify relative risks that can be attributed to the genetic modification
(Wolt et al., 2010). The baseline information includes information regarding the biology of
the parent organism, the comparator and the GE plant, as well as characteristics of the
receiving environment. With respect to the crop it is important to know centre of origin and
taxonomy, plant biology and ecology, survival and persistence in agricultural and seminatural environments, as well as interaction with other organisms (OGTR, 2009). Regarding
the receiving environment, baseline information includes presence of sexually compatible
relatives and/or weedy relatives, mode of pollination (cross vs self), closeness to protected
areas, presence of similar genes in other GE plants, as well as general climatic conditions to
determine gene flow to sexual compatible relatives. Production and uses of the crop as well
as agricultural production practices and implications of coexistence are also considered.
Information about previous releases in the receiving environment or in other countries and its
risk assessment documents and experience is also valuable (OGTR, 2009).
Baseline information is analyzed with the objective to determine whether protection
goals, i.e. biological diversity, ecological protected areas, the avoidance of invasive alien

56

species, could be affected by the GE plant. The analysis is performed according to the
environmental scope defined, i.e. to analyse specifically the impact of the event and not of the
associated technology, to analyse parameters of the agroecosytem and if necessary of the
ecosystem, and to consider coexistence among different production systems.
The criteria defined and baseline information gathered in Problem Context is used for
the next step, Problem Definition. This step is a critical challenge of Problem Formulation
since the objective is to reach a relevant risk hypothesis worthwhile to test. First, plant
attributes that could represent an environmental hazard are characterized (Wolt et al., 2010).
The description of the plant attribute that may cause an environmental concern refers to the
description of the genetic modification, characteristics of the trait that was introduced and the
mechanism by which the gene/trait can cause harm to environmental concerns (Wolt et al.,
2010).
Secondly, based on the plant attributes, the protection goals defined in Problem
Context are translated to environmental values with observable and measurable attributes,
named assessment endpoints, to assess the impact that the release of the specific GE plant
would have on them (US EPA, 1998; Raybould et al., 2010; Wolt et al., 2010). In other
words, the environmental values and assessment endpoints are used as indicators of the
protection goals defined in Problem Context, which generally refer to broad concepts. It is
then necessary to refine them into concrete and manageable parameters for the analysis
(Raybould et al., 2010; Wolt et al., 2010), for example, an environmental value would be
‘protect important beneficial insects such as pollinators’ and its assessment endpoint the
‘abundance of pollinators’ or for the environmental value ‘to protect wild relatives from
becoming invasive species’ the assessment endpoint would be ‘persistence of wild relatives’.
A generic assessment such as “Impact on beneficial insects” is not an assessment endpoint.
The assessment endpoint has to be an explicit expression of the environmental value to be

57

protected such as “abundance of beneficial insects” (Hokanson and Quemada, 2009). For
each protection goal it is necessary to perform a specific problem formulation and risk
characterization.
Third is the creation of a conceptual model in which potential exposure pathways are
generated where the plant attribute (hazard) is linked to specific environmental values and
assessment endpoints to determine if a particular harm could occur (US EPA, 1998;
Raybould, 2006; Raybould et al., 2010; Wolt et al., 2010). Thus, the conceptual model
combines: the plant attribute that has been modified with the mechanism to cause harm; the
biology of the crop engineered; the characteristics of the receiving environment; and the
complex interplay among these factors (Figure 1.1). The conceptual model is used to reach
real environmental scenarios where potential harmful effects of the GE plant overlap with the
environmental value to be protected.
Specifically, an exposure pathway or risk scenario represents the sequence of steps of
the process for a particular harm to occur (Raybould, 2010). The objective is to reach testable
risk hypothesis at each stage of the pathway that will derive from the general question of
what is the probability of harm if the commercial cultivation of the GE crop is authorized. In
this question it is important to specify the changes that could occur with respect to the
environmental values, i.e. to define clearly the harm a priori that is being analyzed
(Raybould, 2010). If the question is left open as to what will happen if a GE crop is released,
it will result in weak broad hypothesis of ‘no difference between transgenic and nontransgenic comparator’ (Raybould et al., 2010), or collection of data that test no hypothesis
(Raybould, 2006, 2010). Thus, in the exposure pathway there should be an arguable and
observable link between the hazard from the GE crop and potential harm to the
environmental value (Nickson, 2008; Raybould et al., 2010; Raybould, 2010; Wolt et al.,

58

2010). A general scheme for a conceptual model considering exposure pathway and risk
hypotheses is presented in Table 1.10 according to Raybould (2010).

Table 1.10. General scheme to state particular pathways with the steps for a
harm to occur according to Raybould (2010).
Exposure pathway

Hypothesis

Cultivation of the GM crop


Event A will not occur

Event A


Event B will not occur

Event B


Event C will not occur

Event C


Event D will not occur

Event D (Harm)

In each step of the exposure pathway can be postulated a testable risk hypothesis.
Testing of these hypotheses is used in risk assessment to estimate the probability of a
particular harm to occur. An important consideration in Problem Formulation is that it is
possible to postulate numerous conceivable exposure pathways that lead to a particular harm
(Raybould et al., 2010). This allows regulators to judge at an early stage of the analysis
whether particular risk scenarios are sufficiently likely to occur to merit a detailed risk
characterization (Raybould et al., 2010).
Each risk hypothesis is corroborated by providing evidence that show if a particular
step of the pathway is possible or not. Evidence at an early stage of the analysis may come
from analysing existing data and baseline information regarding plant attributes and
mechanisms to cause harm, the biology of the crop and characteristics of the receiving

59

environment. Fully exploiting existing data allow ruling out unlikely harms early in the
process, preventing unnecessary further assessment.
A useful guide that can be applied to GE plants to determine if already existing data
can be used for hypotheses testing and risk characterization are the qualitative criteria
described by WHO (2008) for chemical exposure assessment of: (1) Appropriateness: The
degree to which data are relevant and applicable to a particular exposure pathway; (2)
Accuracy: The degree to which measured, calculated, or modeled values correspond to the
true values of what they are intended to represent; (3) Integrity: The degree to which the data
collected and reported are what they purport to be; and (4) Transparency: The clarity and
completeness with which all key data, methods, and processes, as well as the underlying
assumptions and limitations, are documented and available (Romeis et al., 2011).
If a step in the process (Table 1.10) is reached that it is not possible, then the pathway
is blocked and that particular harm can be eliminated from consideration. Nevertheless, for a
good risk communication, even those exposure pathways that are readily ruled out by a first
analysis of baseline information in Problem Context, it is necessary to state how that
particular pathway was considered, and why it was rejected as implausible (Raybould, 2010).
In those exposure pathways for which steps are not blocked by analysing existing
data, the harm warrants further evaluation to assess its likelihood of occurrence. The process
of Problem Formulation will continue with regard to those particular harms developing an
analysis plan to collect necessary data for hypothesis testing and its risk characterization (US
EPA, 1998; Raybould, 2006; Raybould et al., 2010; Wolt et al., 2010). The analysis plan will
include the experiments and measures for those considerations for which the information is
incomplete. The analysis plan is discussed later in this section. In this stage of Problem
Formulation the risk hypotheses postulated are key for the success of decision-making.

60

Raybould (2010) suggests when formulating hypotheses in risk assessment, to avoid
formulating hypothesis that make precise predictions about an exact value of an assessment
endpoint, unless this is required to make a decision. For example, a risk assessment
hypothesis could be ‘transgenic crop A does not hybridize with wild plant B’ rather than, ‘the
precise number of AxB hybrids formed are ‘X’’ (Raybould, 2010). Raybould (2010) indicates
that it is more worthwhile to do research to defining thresholds of indicators than to improve
the precision of prediction of the indicator.
A good risk hypothesis is one for which the result of testing is sufficient to make a
decision whether to authorize the commercial release of a GE crop (Raybould, 2010). In risk
assessment risk hypotheses are formulated considering pathways where the cultivation of a
GE crop will cause harm to environmental values. Risk hypotheses at each step of the
exposure pathway of a harm (Table 1.10) postulates that such particular step will not occur
either because the process does not exist or it occurs below a defined threshold (Raybould,
2010). The corroboration or falsification of these risk hypotheses should be able to determine
the risk level implied in the use of a GE crop. Therefore, in risk assessment the null
hypothesis corresponds to a general or default position of no harm to specific endpoints. For
example a null hypothesis might be: ‘transgene will not confer a selective advantage to GE
crop’. The alternative hypothesis does not need to be the opposite of the null hypothesis, it
predicts the results of the experiment if the alternative hypothesis is true. One example would
be: ‘transgene will confer a selective advantage to GE crop resulting in increased
weediness’.
As is the case for the scientific method, hypothesis testing in risk assessment does not
provide an absolute truth. Experimental data and observations on a sample are used to make
inferences regarding the population. The null hypotheses can never be proven, experimental
evidence can only reject a null hypothesis or be insufficient to reject it (Raybould et al.,

61

2010). For example, if data on number of volunteer plants and persistence shows no
statistically significant difference between transgenic and non-transgenic plants, it is not
correct to assume that there is no difference in reality. The correct conclusion is that there is
not enough evidence to reject the null hypothesis, i.e. the experiment failed to reject the null
hypothesis.
Null hypotheses cannot be proven true when are not rejected because there could be a
Type II error (which probability is called ), i.e., when the null hypothesis is not rejected but
in reality is false, therefore the transgene will in reality confer a selective advantage. Table
1.11 shows a schematic of the situation that corresponds to a Type I error or Type II error in
risk assessment. A Type II error happens in risk assessment when a negligible risk level is
predicted, but the actual level of risk is higher than negligible. The probability of a Type II
error depends on the infinite possible values of the alternative hypothesis. It is difficult to
estimate and therefore  is not controllable or fixed by the researcher. Thus, failing to reject
the null hypothesis does not provide security that the transgene ‘will not confer a selective
advantage to GE crop’.

Table 1.11. Schematic representation of statistical Type I error and Type II error applied in
risk assessment.
Estimated level of postulated risk
Greater than
negligible
Greater than
negligible

True positive

False negative
(Type II error)

Negligible

Actual level of risk

Negligible

False positive
(Type I error)

True negative

Source: Modified from Keese, 2010.

On the other hand, if experimental data give enough evidence to reject the null
hypothesis, a Type I error could occur, i.e. the null hypothesis is rejected, but in reality it is
true, and therefore the transgene will not confer a selective advantage. A Type I error
62

happens in risk assessment when a risk level greater than negligible is predicted but the actual
level of risk is negligible. A Type I error is controllable and fixed by the researcher.
Experiments to test the null hypothesis should be designed with the lowest probability of a
Type I error () determining the highest confidence ((1-)100%). The controversy lies in the
fact that as shown in Figure 1.4 if  decreases,  increases, supporting the fact that a null
hypothesis cannot be proven. However, the weight-of-evidence approach is useful in risk
assessment. If the null hypothesis is supported time and time again, the weight-of-evidence
becomes convincing that the relationship between the transgene conferring a selective
advantage and the GE crop acquiring increased weediness does not exist (Raybould, 2010).
This provides predictability reducing uncertainty.

Source: http://www.stattools.net/Probability_Exp.php
Figure 1.4. Summary diagram of Type I and II errors. “For interpretation of the references to
color in this and all other figures, the reader is referred to the electronic version of this
thesis”.

For those exposure pathways that merit further consideration, an analysis plan is
elaborated. The analysis plan includes the selection of parameters that can be used to
measure the attributes of the environmental value as well as the experimental design for

63

hypothesis testing. High confidence in the risk assessment result is based on the thoroughness
with which hypotheses are tested (Raybould, 2010).
A crucial step is to make appropriate selection of parameters of the environmental
value that are going to be measured during hypothesis testing. This decreases the probability
of having Type I and II errors.
Finally, once the analysis plan is carried forward, the data collected are used to
perform the Risk Characterization. Risk characterization is formulated in terms of probability
as a function of the probability of harm to occur by the consequences of the harm (Figure
1.3). Risk characterization defines the specific harm that can effectively happen to the
environment (Raybould, 2006; Wolt et al., 2010). This harm will be a function of the
likelihood of exposure of the environmental value to the hazard (exposure pathway) and the
consequences of the exposure to the hazard.

CONCLUSIONS AND OBJECTIVES
The slow but steady tendency toward new genes, traits, crops and locations raise new
challenges in environmental risk assessment. Regulation is considered to be one of the main
limitations for the adoption of crop biotechnologies and several authors express the need for
regulatory systems that are capable, appropriate to the needs, and time and cost effective
(Nap et al., 2003; Bradford et al., 2005; Wolt et al., 2009; Bayer et al., 2010; James, 2010,
2011, 2012).
The objectives of my thesis are to:
1) Analyze the criteria and principles required for the implementation of a biosafety
framework considering situations particular to developing countries, describe the experience
implementing a new biosafety framework in Uruguay, and analyze the possibility of
harmonization between regulatory systems, and

64

2) Examine possible secondary unexpected effects with respect to complex traits and
to determine an approach for its analysis within the context of the risk assessment phase.
Chapter II is titled: ‘Establishment and analysis of the Uruguayan regulatory system
for genetically engineered crops’. This chapter describes the Uruguayan experience
implementing a new regulatory system after an 18- month moratorium (suspension) period
imposed by a Decree since January 2007. This chapter analyzes the process of building a
biosafety framework with emphasis on the criteria and principles required for the risk
assessment phase.
Chapter III is titled: ‘Comparison of the Uruguayan regulatory system for genetically
engineered crops to other national and regional systems and potential for harmonization’. In
this chapter the Uruguayan approach for the establishment of a biosafety framework is
compared with those of Argentina, Brazil and Paraguay, which together form the Southern
Common Market (MERCOSUR for its acronym in Spanish). The possibility of
harmonization in specific aspects of the regulatory systems is also discussed.
Chapter IV is titled: ‘Application of the Problem Formulation approach when
assessing environmental risks of crops engineered with complex traits - a case study of
dehydration stress tolerance in cucumber’. In this chapter the methodology of Problem
Formulation is applied to the risk assessment process considering the Uruguayan biosafety
framework and using the case study of cucumber plants engineered with the Arabidopsis
thaliana transcription factor gene CBF to confer dehydration stress tolerance. Possible
secondary unexpected effects are analyzed with respect to general complex traits.
The information provided in this thesis is based on scientific literature, published
documents, unpublished public official documents, my personal experience working for the
Uruguayan regulatory system and personal communication with national, regional and
international regulators.

65

APPENDIX

66

APPENDIX

Table A1.1. List of crops with commercial approval, number of events and traits description.

CROP

Number of
events with
regulatory
approval

Soybean
(Glycine max L.)

13

Corn
(Zea mays L.)

58

Cotton
(Gossypiumhirsutum L.)

21

Argentina Canola
(Brassicanapus)

15

Polish Canola
(Brassica rapa)
Wheat
(Triticumaestivum)
Rice
(Oryzasativa)
Alfalfa
(Medicago sativa L.)
Creeping Bentgrass
(Agrostisstolonifera L.)
Papaya
(Carica papaya)
Squash
(Cucurbita pepo)
Sugarbeet
(Beta vulgaris)
Potato
(Solanumtuberosum L.)

2
1
2
1
1

Traits
(1)
(2)
(4)
(5)
(1)
(2)
(6)
(7)
(8)
(9)
(1)
(2)
(1)
(4)
(5)
(6)
(10)
(1)
(1)
(1)
(1)
(1)

2

(3)

1

(3)

3

(1)

5

Tomato
(Lycopersiconesculentum)

7

67

(2)
(3)
(2)
(3)
(12)
(13)

Table A1.1 (cont’d)
Melon
(Cucumismelo L.)
Sweet pepper
(Capsicum annuum)
Chicory
(Cichoriumintybus L.)
Tobacco
(Nicotianatabacum)
Flax/Linseed
(LinumusitatissimumL.L.)
Poplar
(PopulustremulaXPopulus alba)
Plum
(Prunusdomestica L.)
Petunia
(Petunia hybrida)

1

(12)

1

(3)

1

(1) and (14)

2

(1)
(15)

1

(1)

1

(2)

1

(3)

1

Carnation
(Dianthus caryophyllus)

3

(16)
(1)
(16)
(17)

Rose
2
(16)
(Rosa hybrida)
Beans
1
(3)
(1) Herbicide tolerance
(2) Insect resistance
(3) Virus resistance
(4) High oleic acid
(5) Low linolenic acid
(6) Male sterility
(7) Heat stable alpha-amylase for dry grind ethanol process
(8) Enhanced lysine content
(9) Reduced yield loss under water deficit (cold shock protein B)
(10) High laurate and myristate acids
(11) Altered starch composition
(12) Delayed ripening
(13) Delayed softening
(14) Fertility restored
(15) Reduced nicotine content
(16) Modified flower color
(17) Delayed senescence

68

REFERENCES

69

REFERENCES

Agüero T. 2011. Bioseguridad en Chile, novedades. In: Jornada de Biotecnología,
Bioseguridad y Bioemprendimientos en la Región. Octubre, 2011, Montevideo,
Uruguay.
Andow DA, Hilbeck A. 2004. Science-Based Risk Assessment for Nontarget Effects of
Transgenic Crops. BioScience 54(7):637-649.
ARGENTINA. Ministry of Agriculture (MINAGRI). 2003. Decree 39/003
ARGENTINA. Ministry of Agriculture (MINAGRI). 2011. Decree 701/011
ARGENTINA. National Advisory Commission on Agricultural Biotechnology (CONABIA).
2013. Commercial OGM.
http://64.76.123.202/site/agregado_de_valor/biotecnologia/55OGM_COMERCIALES/index.php
Baker HG. 1974. The evolution of weeds. Annual Review of Ecology and Systematics. 5:124.
Barnthouse LW. 1994. Issues in Ecological Risk Assessment: The CRAM Perspective.
RiskAnalysis 14(3):251-256.
Barton JE and Dracup M. 2000. Genetically Modified Crops and the Environment. Agron. J.
92:797–803.
Bayer, Norton, and Falck Zepeda. 2010. Cost of Compliance with Biotech Regulation in the
Philippines: Developing Countries. AgBioForum 13(1): 53-62.
Berg P, Baltimore D, Brenner S, Roblin RO and Singer MF. 1975. Summary Statement of the
Asilomar Conference on Recombinant DNA Molecules. Proc. Nat. Acad. Sci. 72:19811984.
Biosafety Clearing House (BCH), Convention on Biological Diversity. 2013.
http://bch.cbd.int/
Bradford K, Van Deynze A, Gutterson N, Parrott W and Strauss SH. 2005. Regulating
transgenic crops sensibly: lessons from plant breeding, biotechnology and genomics.
Nature Biotechnology 23(4): 439-444.
BRAZIL. National Biosafety Technical Commission (CTNBio). 2007. Resolution No. 3,
08/16/07. Monitoring norms of genetically modified corn in commercial use.
http://www.ctnbio.gov.br/index.php/content/view/12859.html
__________. 2009. Parecer Técnico nº 2236/2009 - Liberação Comercial de Soja
Geneticamente Modificada Tolerante aos Herbicidas do Grupo Químico das
70

Imidazolinonas, Soja CV127, Evento BPS-CV127-9 - Processo nº 01200.000010/200906 http://www.ctnbio.gov.br/index.php/content/view/14472.html
__________. 2011. Resolution No. 9, 12/02/11. Monitoring norms of genetically modified
organisms post-commercial release.
http://www.ctnbio.gov.br/index.php/content/view/16781.html
__________. 2011. Parecer Técnico nº 3024/2011 - Liberação Comercial de feijoeiro
geneticamente modificado resistente ao vírus do mosaico dourado do feijoeiro (Bean
golden mosaic vírus - BGMV), evento de transformação Embrapa 5.1 - Processo nº
01200.005161/2010-86. http://www.ctnbio.gov.br/index.php/content/view/16659.html
__________. 2013. Commercial Approvals.
http://www.ctnbio.gov.br/index.php/content/view/12786.html
Brookes G and Barfoot P. 2006. GM Crops: The First Ten Years - Global Socio-Economic
and Environmental Impacts. International Service for the Acquisition of Agri-biotec
Applications, ISAAA Brief No. 36.
http://www.isaaa.org/resources/publications/briefs/default.asp
Brookes G. 2008. Economic impacts of low level presence of not yet approved GMOs on the
EU food sector. Briefing document. GBC Ltd, UK. 48p.
Burke JM and Rieseberg. 2003. Fitness effects of transgenic disease resistance in sunflower.
Science 300:1250.
CANADIAN FOOD INSPECTION AGENCY (CFIA).2013. Plants with novel traits.
Website http://www.inspection.gc.ca/plants/plants-with-noveltraits/eng/1300137887237/1300137939635
Carpenter J, Felsot A, Goode T, Hammig M, Onstad D and Sankula S. 2002. Comparative
Environmental Impacts of Biotechnology-derived and Traditional Soybean, Corn, and
Cotton Crops. Council for Agricultural Science and Technology Ames, Iowa.
www.cast-science.org. Sponsored by the United Soybean Board.
www.unitedsoybean.org pp.200.
Castiglioni P, Warner D, Bensen RJ, Anstrom DC, Harrison J, Stoecker M, Abad M, Kumar
G, Salvador A, D’Ordine R, Navarro S, Back A, Fernandes M, Targolli J, Dasgupta S,
Bonin Ch, Luethy MH and Heard JE. 2008. Bacterial RNA Chaperones Confer Abiotic
Stress Tolerance in Plants and Improved Grain Yield in Maize under Water-Limited
Conditions. Plant Physiol. 147:446–455.
Center for Environmental Risk Assessment (CERA). 2013. http://www.ceragmc.org/?action=gm_crop_database
Cerdeira AL and Duke SO. 2006. The current status and environmental impacts of
glyphosate-resistant crops: a review. J. Environ. Qual. 35:1633-1658.

71

Cerdeira AL, Gazziero DLP, Duke SO and Matallo MB. 2011. Agricultural impacts of
glyphosate-resistant soybean cultivation in South America. J. Agric. Food Chem.
59(11):5799-5807.
Chan Z, Bigelow PJ, Loescher W, Grumet R. 2011. Comparison of salt stress resistance
genes in transgenic Arabidopsis thaliana indicates that extent of transcriptomic change
may not predict secondary phenotypic or fitness effects. Plant Biotechnology Journal
pp. 1–17.
CODEX ALIMENTARIUS. 2003. Guideline for the conduct of food safety assessment of
foods derived from recombinant-DNA plants. Codex Alimentarius Commission, Joint
FAO/WHO Food Standards Programme, Rome. CAC/GL 45.
http://www.fao.org/docrep/011/a1554e/a1554e00.htm
Cohen JI. 2005. Poorer national turn to publicly developed GM corps. Nature Biotechnology
1(23):27-33.
Conner AJ, Glare TR and Nap J. 2003. The release of genetically modified crops into the
environment. Part II. Overview of ecological risk assessment. Plant J. 33:19-46.
Convention on Biological Diversity (CBD). 1992. United Nations Environment Programme.
30p. http://www.cbd.int/
Cook RJ. 1999. Science-Based Risk Assessment for the Approval and Use of Plants in
Agricultural and Other Environments. Agricultural Biotechnology and the Poor: 126130.
Cordts J. 2011. APHIS regulatory framework and management goals. In: Problem
Formulation for the environmental risk assessment of RNAi Plants, June 1-3, 2011,
Washington DC, USA. Conference Proceedings. Washington DC, USA. Ed. Center for
Environmental Risk Assessment. pp 11-12.
Craig W, Tepfer M, Degrassi G and Ripandelli D. 2008. An overview of general features of
risk assessments of genetically modified crops. Euphytica 164:853–880.
Dale PJ, Clarke B and Fontes E. 2002. Nature Biotechnology 20(6):567-573.
Dale PJ. 1992. Spread of Engineered Genes to Wild Relatives. Plant Physiol. 100:13-15.
Demeke T, Perry DJ and Scowcroft WR. 2005. Adventitious presence of GMOs: Scientific
overview for Canadian grains. Can.J.Plant Sci. 86:1-23.
Directive 90/220/EEC. Official Journal of the European Communities L 200: 22-33.
Ellstrand NC and Hoffman CA. 1990. Hybridization as an Avenue of Escape for Engineered
Genes. Strategies for risk reduction. BioScience 6(40):438-442.
Ellstrand NC, Prentice HC and Hancock JF. 1999. Gene flow and introgression from
domesticated plants into their wild relatives. Annu. Rev. Ecol. Syst. 30:539–563.
72

Ellstrand NC. 2001. When transgenes wander, should we worry? Plant Physiol. 125:15431545.
EUROPEAN COMMISSION (EC).2000. First Report on the Harmonisation of Risk
Assessment Procedures. Part Two: Appendices. Directorate C – Scientific Opinions
(European Commission Health & Consumer Protection Directorate-General, ed.), p.
261, The European Commission.
__________. 2001. Directive 2001/18/EC of the European Parliament and of the Council, on
the deliberate release into the environment of genetically modified organisms, 12
March 2001.
__________. 2002a. Commission Decision (2002/623/EC) of 24 July 2002 establishing
guidance notes supplementing Annex II to Directive 2001/18/EC of the European
Parliament and of the Council on the deliberate release into the environment of
genetically modified organisms and repealing Council
__________. 2002b. Regulation (EC) No 178/2002 of the European Parliament and of the
Council of 28 January 2002 laying down the general principles and requirements of
food law, establishing the European Food Safety Authority and laying down procedures
in matters of food safety. Official Journal of the European Communities L 31:1-24.
European Food Safety Authority (EFSA) Panel on Genetically Modified Organisms (GMO).
2006. Guidance document of the Scientific Panel on Genetically Modified Organisms
for the risk assessment of genetically modified plants and derived food and feed. EFSA
Journal 99, pp. 1-100.
__________. 2010. Guidance on the environmental risk assessment of genetically modified
plants. EFSA Journal 8(11):1879 1- 111.
__________. 2011. Guidance document on Selection of Comparators for the Risk
Assessment of GM Plants. EFSA Journal 9(5):2149 21p.
__________. 2011. Guidance for risk assessment of food and feed from genetically modified
plants. EFSA Journal 9(5):2150 37p.
Fernandez M. and McCammon S. 2007. Emerging challenges for biotech specialty crops.
Workshop Report, January 18-19, 2007, Pew Initiative on Food and Biotechnology.
18p.
Flint J, Gil L, Verastegui J, Irarrazabal C and Dellacha J. 2000. Biosafety information
management systems. A comparative analysis of the regulatory systems in Canada,
Argentina, and Chile. EJB Electronic Journal of Biotechnology 3(1):9-29.
Food and Agriculture Organization of the United Nations. (FAO). 2007. Instrumentos de la
FAO sobre la bioseguridad (Biosecurity toolkit). Roma, Italia. 148p.

73

Food and Agriculture Organization of the United Nations. (FAO)/ World Health Organization
(WHO). 1996. Biotechnology and Food Safety. Report of a Joint FAO/WHO
Consultation, Rome, Italy, 30 September±4 October 1996. FAO Food and Nutrition
Paper 61. Rome: Food and Agriculture Organization of the United Nations.
http://www.fao.org/es/esn/gm/biotec-e.htm
__________. 2000a. Report of the First Session of the Codex ad hoc Intergovernmental Task
Force on Foods Derived from Biotechnology (ALINORM 01/34). Rome: Food and
Agriculture Organization of the United Nations. http://www.fao.org/es/esn/gm/biotece.htm
__________. 2000b. Safety Aspects of Genetically Modifed Foods of Plant Origin. Report of
a Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology,
Geneva, Switzerland, 29 May±2 June 2000. Rome: Food and Agriculture Organisation
of the United Nations. http://www.fao.org/es/esn/gm/biotece.htm
Garcia-Alonso M, Jacobs E, Raybould A, Nickson TE, Sowig P, Willekens H, Van Der
Kouwe V, Layton R, Amijee F, Fuentes AM and Tencalla F. 2006. A tiered system for
assessing the risk of genetically modified plants to non-target organisms.
Environmental Biosafety Research 5:57-65.
García-Alonso M. 2010. Using problem formulation in environmental risk assessments:
practical methods for the assessment of unintended effects. In: International
Symposium on the Biosafety of Genetically Modified Organisms (11th, 2010, Buenos
Aires, Argentina). Proceedings. International Society for Biosafety Research (ISBR).
pp. 55.
García-Huidobro TC. 2011. Biosafety in the Caribbean: Creating capacities through a
regional GEF project. Power point presentation. In: Videoconference “Estado mundial
de la comercialización de cultivos biotecnológicos en 2010 según el informe #42 del
ISAAA.”, May 17-18, 2011, IICA. www.iica.org.uy - www.iica.int
Grumet R and Gifford F. 1988. Plant biotechnology in the United States: Issues and
challenges en route to commercial production. HortScience 33:187-192.
Grumet R, Wolfenbarger LR, Ferenczi A. 2011. Future possible genetically engineered crops
and traits and their potential environmental impacts. In: Grumet G, Hancock J, Maredia
K and Weebaddee C. ed. Environmental Safety of Genetically Engineered Crops. East
Lansing, USA, Michigan State University pp 47-57.
Hails RS and Morley K. 2005. Genes invading new populations: a risk assessment
perspective. Trends in Ecology and Evolution 20(5):245-252.
Halfhill MD, Sutherland JP, Moon HS, Poppy GM, Warwick SI, Weissinger AK, Rufty TW,
Raymer PL and Stewart Jr CN. 2005. Growth, productivity, and competitiveness of
introgressed weedy Brassica rapa hybrids selected for the presence of Bt cry1Ac and
gfp transgenes. Molecular Ecology 14:3177–3189.
74

Hancock JF, Grumet R and Hokanson SC. 1996. The Opportunity for Escape of Engineered
Genes from Transgenic Crops. Hortscience 31(7):1080-1085.
Hancock JF. 2003. A framework for assessing the risk of transgenic crops. Bioscience
53:512-519.
Hill RA and Sendashonga C. 2003. Review. General principles for risk assessment of living
modified organisms: Lessons from chemical risk assessment. Environ. Biosafety Res.
2:81-88.
Hokanson K. and Ferenczi A. 2011. Systems to regulate genetically engineered plants.
Similarities and differences among countries. In: Grumet G, Hancock J, Maredia K and
Weebaddee C. ed. Environmental Safety of Genetically Engineered Crops. East
Lansing, USA, Michigan State University pp 147-155.
Hokanson K. and Quemada H. 2009. Improving environmental risk assessment. Problem
Formulation and Tiered Testing. Program for Biosafety Systems. Presentation at
SEARCA Agriculture and Development Seminar Series, USA, 28 April, 2009.
Information Systems for Biotechnology (ISB), National Resource in Agbiotech Information,
Virginia Tech http://www.isb.vt.edu/ , 2012.
International Organization for Standardization. 2005. ISO 22000 for food safety including
risk analysis methodology and identification of critical points.
http://www.iso.org/iso/home/search.htm?qt=22000&published=on&active_tab=standar
ds&sort_by=rel
__________. 2009. ISO 31000 for risk management, principles and guidelines.
http://www.iso.org/iso/home/search.htm?qt=31000&published=on&active_tab=standar
ds&sort_by=rel
International Service for the Acquisition of Agri-biotech Applications (ISAAA). 2013. GM
approval database. http://www.isaaa.org/gmapprovaldatabase/default.asp
Interregional Research Project No. 4 (IR4). http://ir4.rutgers.edu/
Jaffe G. 2004. Regulating transgenic crops. A comparative analysis of different regulatory
processes. Transgen. Res. 13:5-19.
James C. 2010. Global Status of Commercialized Biotech GM Crops. International Service
for the Acquisition of Agri-biotech Applications, ISAAA Brief No.42.
http://www.isaaa.org/resources/publications/briefs/42/default.asp
__________. 2011. Global Status of Commercialized Biotech GM Crops. International
Service for the Acquisition of Agri-biotech Applications, ISAAA Brief No. 43.
http://www.isaaa.org/resources/publications/briefs/43/default.asp

75

__________. 2012. Global Status of Commercialized Biotech GM Crops. International
Service for the Acquisition of Agri-biotech Applications, ISAAA Brief No. 44.
http://www.isaaa.org/resources/publications/briefs/44/executivesummary/default.asp.
Jenczewski E, Ronfort J and Chèvre AM. 2003. Crop-to-wild gene flow, introgression and
possible fitness effects of transgenes. Environ. Biosafety Res. 2:9-24.
Kalaitzandonakes N, Alston JM and Bradford KJ. 2007. Compliance costs for regulatory
approval of new biotech crops. Nature Biotechnology 25(5):509-511.
Keeler KH. 1989. Can genetically engineered crops become weeds? Bio/Technology 7:11341139.
Keese P. 2008. Review article. Risks from GMOs due to Horizontal Gene Transfer. Environ.
Biosafety Res. 7: 123–149.
Kock M and Massey A. 2011. Risk-Benefit communication for transgenic crops. In: Grumet
G, Hancock J, Maredia K and Weebaddee C. ed. Environmental Safety of Genetically
Engineered Crops. East Lansing, USA, Michigan State University pp 175-187.
Kuiper HA, Kleter GA, Noteborn HPJ and Kok EJ. 2001. Assessment of the food safety
issues related to genetically modified foods. Plant Journal 27(6):503-528.
Little HA, Grumet R and Hancock JF. 2009. Modified Ethylene Signaling as an Example of
Engineering for Complex Traits: Secondary Effects and Implications for Environmental
Risk Assessment. Hortscience 44(1):94–101.
Lövei GL and Arpaia S. 2005. The impact of transgenic plants on natural enemies: a critical
review of laboratory studies. The Netherlands Entomological Society Entomologia
Experimentalis et Applicata 114:1–14.
MacKenzie DJ. 2000. International comparison of regulatory frameworks for food products
of biotechnology. Canadian Biotechnology Advisory Committee (CBAC). 62p.
Markle G, Baron JJ and Holm R. 2001. Minor use pesticides, registrarion IR-4 Program. 37p.
McCammon S. 2010. Low-Level Presence (LLP): United States. In: Workshop on AP/LLP,
May 4-5, Buenos Aires, Argentina, Seed Association of the Americas (SAA). 25p.
McHugen A and Smyth S. 2008. US regulatory system for genetically modified (genetically
modified organism (GMO), rDNA or transgenic crop cultivars. Plant Biotechnology J.
6:2-12.
Mclean MA, Frederick RJ, Traynor PL, Cohen JI and Komen J. (Eds). 2003. A framework
for biosafety implementation: report of a meeting. The Hague, The Netherlands:
International Service for National Agriculture Research (ISNAR) Biotechnology
Service, July 2001, Washington, DC, USA. 57p.

76

Monsanto Company. 2009. Petition for the determination of non-regulated status for
MON87460-4 Corn. Submitted by Reeves WR. Regulatory Affairs Manager. Monsanto
Petition Number: 07-CR-191U. 561p.
__________. 2011. Petition for the determination of non-regulated status for MON87460-4
Corn. Monsanto Petition Number: 07-CR-191U. Final environmental assessment. 125p.
__________. 2011. Petition for the determination of non-regulated status for MON87712-4
Soybean. Submitted by Koyejo TO. Regulatory Affairs Manager. Monsanto Petition
Number: 11-SY-217U. 467p.
Moose SP and Mumm RH. 2008. Molecular plant breeding as the foundation for 21st century
crop improvement. Plant Physiology 147:969-977.
Nap JP, Metz PLJ, Escaler M and Conner AJ. 2003. The release of genetically modified crops
into the environment Part I. Overview of current status and regulations. The Plant
Journal 33:1–18.
National Institutes of Health (NIH). 1976. Recombinant DNA research. Guidelines. Federal
Register 41:27 902 - 27 911 - 27 943.
__________. 1978. Guidelines for research involving recombinant DNA molecules. Federal
Register, 43:60 108.
Naylor RL, Falcon WP, Goodman RM, Jahn MM, Sengooba T, Tefera H and Nelson RJ.
2004. Biotechnology in the developing world: a case for increased investments in
orphan crops. Food Policy 29:15-44.
NEW ZELAND. 1993. Biosecurity Act. 356p.
__________. 1996.Hazardous Substances and New Organisms Act (HSNO Act). 309p.
Nickson TE. 2008. Planning environmental risk assessment for genetically modified crops:
Problem Formulation for stress-tolerant crops. Plant Physiol. 147:494-502.
Nielsen KM, Bones AM, Smalla K and Van Elsas JD. 1998. Horizontal gene transfer from
transgenic plants to terrestrial bacteria - a rare event? FEMS Microbiology Reviews
22:79-103.
Office of Orphan Product Development (OOPD-FDA). 2013. Homepage.
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/O
fficeofScienceandHealthCoordination/ucm2018190.htm).
Office of the Gene Technology Regulator (OGTR). 2001. Risk assessment framework for
license applications to the office of the gene technology regulator, Canberra, Australia.
Organization for Economic Co-operation and Development (OECD). 1986. Safety
considerations for industrial, agricultural and environmental applications of organisms
derived by recombinant DNA techniques.
77

__________. 1993. Safety considerations for biotechnology: scale-up of crop plants. 43p.
__________. 1995. Harmonization of biotechnology regulation: Analysis of information
elements used in the assessment of certain products of modern biotechnology. OECD
Environment Monograph No. 100, Paris, France.
__________. 2009. Biotechnologies in agriculture and related natural resources to 2015.
OECD Journal: General Papers Vol 2009/3. 105p.
Ortíz GS. 2011. Comentarios sobre las recientes aprobacones de maíz GM en México. Power
Point presentation. In: Cultivos biotecnológicos en México. In: Videoconference
“Estado mundial de la comercialización de cultivos biotecnológicos en 2010 según el
informe #42 del ISAAA.”, May 17-18, 2011, IICA. www.iica.org.uy - www.iica.int
Paraguay. Agricultural and Forestry National Biosafety Commission (CONBIO). 2013.
http://www.mag.gov.py/#
Patton DE. 1998. Environmental risk assessment: tasks and obligations. Hum Ecol. Risk
Assess. 4(3):657-670.
PERU. Ministry of Agriculture (MINAG). 2011a. Decree No. 003-2011-AG. Reglamento
Interno Sectorial sobre seguridad del adecuado uso de la biotecnología para el sector
Agricultura. Diario Oficial El Peruano, 15 de abril 2011, pp. 441066.
__________. Congress of the Republic. 2011b. Law No. 29811. Ley que establece la
moratoria al ingreso y producción de organismos vivos modificados al territorio
nacional por un período de 10 años. Diario Oficial El Peruano, 9 de diciembre 2011,
454601.
__________. Ministry of Environment (MINAM). 2012. Decree No. 008-2012-MINAM.
Reglamento de la ley que establece la moratoria al ingreso y producción de organismos
vivos modificados al territorio nacional por un período de 10 años. Diario Oficial El
Peruano, 14 de noviembre 2012, 478572.
Pilson D and Prendeville HR. 2004. Ecological effects of transgenic crops and the escape of
transgenes into wild populations. Annu. Rev. Ecol. Evol. Syst. 35:149-74.
Power M. and McCarty LS. 1998. A comparative analysis of environmental risk
assessment/risk management frameworks. Environmental Science and Technology
News. 224-231p.
Ramessar K, Capell T, Twyman RM, Quemada H and Christou P. 2009. Calling the tunes on
transgenic crops: the case for regulatory harmony. Mol. Breeding 23:99-112.
Raybould AF, Gray AJ. 1993. Genetically modified crops and hybridization with wild
relatives: a UK perspective. J Appl Ecol 30:199–219.

78

Raybould A. 2006. Problem formulation and hypothesis testing for environmental risk
assessments of genetically modified crops. Environ Biosafety Res 5:119–125.
__________. 2006. Problem Formulation for environmental risk assessment of genetically
modified plants. In: 9th Symposium on the Biosafety of genetically modified
organisms. Biosafety research and environmental risk assessment. Jeju Island, Korea,
September 24-29. pp. 47-51.
__________. 2010. Reducing uncertainty in regulatory decision-making for transgenic crops.
More ecological research or clearer environmental risk assessment? GM Crops 1(1):17. Landes Bioscience.
Raybould A, Tuttle A, Shore S, Stone T. 2010. Environmental risk assessments for transgenic
crops producing output trait enzymes. Transgenic Res 19:595–609.
Raybould A, Higgins LS, Horak MJ, Layton RJ, Storer NP, De La Fuente JM and Herman
RA. 2011. Assessing the ecological risks from the persistence and spread of feral
populations of insect-resistant transgenic maize. Transgenic Res DOI 10.1007/s11248011-9560-4.
Ríos A, Fernandez G and Collares L. 2005. Study of weed communities associated with notill production systems in Uruguay. INIA. Seminario-Taller Iberoamericano, Colonia
del Sacramento, Uruguay. 13p.
Romeis J, Bartsch D, Bigler F, Candolfi MP, Gielkens MMC, Hartley SE, Hellmich RL,
Huesing JE, Jepson PC, Layton R, Quemada H, Raybould A, Rose RI, Schiemann J,
Sears MK, Shelton AM, Sweet J, Vaituzis Z and Wolt JD. 2006. Moving Through the
Tiered and Methodological Framework for Non-Target Arthropod Risk Assessment of
Transgenic Insecticidal Crops. In:9th International Symposium on the Biosafety of
Genetically Modified Organisms, Jeju Island, Korea, pp. 62-67.
Romeis J, Bartsch D, Bigler F, Candolfi MP, Gielkens MMC, Hartley SE, Hellmich RL,
Huesing JE, Jepson PC, Layton R, Quemada H, Raybould A, Rose RI, Schiemann J,
Sears MK, Shelton AM, Sweet J, Vaituzis Z and Wolt JD. 2008. Assessment of risk of
insect-resistant transgenic crops to nontarget arthropods. Nature Biotechnlogy
26(2):203-208.
Romeis J, Hellmich RL, Candolfi MP, Carstens K, De Schrijver A, Gatehouse AMR, Herman
RA, Huesing JE, Mclean MA, Raybould A, Shelton AM and Waggoner A. 2011.
Recommendations for the design of laboratory studies on non-target arthropods for risk
assessment of genetically engineered plants. Transgenic Res 20:1–22.
Sanvido O, Stark M, Romeis J and Bigler F. 2006. Ecological impacts of genetically
modified crops. Experiences from ten years of experimental field research and
commercial cultivation. Swiss Confedeartion, Agroscope Reckenholz-Tanikon
Researth Station (ART). ART-Schriftenreihe 1.

79

Sears MK, Hellmich RL, Stanley-Horn DE, Oberhauser KS, Pleasants JM, Mattila HR,
Siegfriedi BD and Dively GP. 2001. Impact of Bt corn pollen on monarch butterfly
populations: A risk assessment. PNAS Early Edition: 1-6.
Secretariat of the Convention on Biological Diversity (2000). Cartagena Protocol on
Biosafety to the Convention on Biological Diversity: text and annexes. Montreal:
Secretariat of the Convention on Biological Diversity. 30p.
Snow AA and Morán Palma P. 1997. Commercialization of Transgenic Plants: Potential
Ecological Risks. Will evolutionary effects of engineered crops exacerbate weed and
pest problems? BioScience 47(2):86-96.
Snow AA, Pilson D, Rieseberg LH, Paulsen MJ, Pleskac N, Reagon MR, Wolf DE and
Selbo SM. 2003. A Bt Transgene Reduces Herbivory And Enhances Fecundity In Wild
Sunflowers. Ecological Applications 13(2):279–286.
Snow AA, Andow DA, Gepts P, Hallerman M, Power A., Tiedje JM and Wolfenbarger LL.
2005. Genetically engineered organisms and the environment. Current status and
recommendations. Ecological Applications 15(2):377-404.
Solleiro JL and Galvez A. 2002. Latin American biosafety regulatory framework. Int. J.
Biotechnol. 4:306-320.
Souto G. 2012. Oleaginosos y derivados: situación y perspectivas. In: Anuario 2012, Oficina
de Programación y Política Agropecuaria (OPYPA), Ministerio de Ganadería
Agricultura y Pesca (MGAP), Montevideo, Uruguay. pp 123-135.
Souto G. and Ferenczi A. 2010. Genetically Modified Organisms: Progress in the
implementation of the new regulatory system. In: Annual Book of the Office of
Planning and Agricultural Policy of the Ministry of Livestock, Agriculture and
Fisheries (MGAP-OPYPA) December, 2010. Montevideo, Uruguay. pp.278-285.
Specialty Crop Regulatory Assistance (SCRA).2013. Homepage.
http://specialtycropassistance.org/.
Stein AJ and Rodríguez-Cerezo E. 2009. The global pipeline of new GM crops. Implications
of asynchronous approval for international trade. European Commission, Joint
Research Centre JRC, EUR 23486 EN. 114p.
Stein AJ and Rodríguez-Cerezo E. 2010. Low-Level Presence of New GM Crops: An Issue
on the Rise for Countries Where They Lack Approval. AgBioForum 13(2):173-182.
Stewart Jr CN, Halfhill MD and Warwick SI. 2003. Transgene introgression from genetically
modified crops to their wild relatives. Nature Reviews Genetics 4:806-817.
Syvanen M. 1999. In search of horizontal gene transfer. Nature Biotechnology 17:833.

80

Thomashow MF. 2001. So What’s New in the Field of Plant Cold Acclimation? Lots! Plant
Physiol. 125:89–93.
Toenniessen GH, O’Tooley JC and DeVriesz J. 2003. Advances in plant biotechnology and
its adoption in developing countries. Current Opinion in Plant Biology 6:191–198.
Traynor PL, Frederick RJ, Koch M. 2002. A workbook for technical training. Biosafety and
risk assessment in agricultural biotechnology. The agricultural biotechnology support
project, Institute of International Agriculture, Michigan State University. Lansing, MI.
142p.
United Nations Environment Programme (UNEP). 2005. A biosafety framework
development Toolkit, Phase 3, Part I: Formulation of the regulatory regime. 46p.
http://www.unep.org/tools/default.asp?ct=biosafe
United States Department of Agriculture (USDA). 2007. Specialty Crop Research Initiative,
Farm Bill
http://www.usda.gov/wps/portal/usda/usdahome?navid=FARM_BILL_FORUMS
URUGUAY, MGAP-MVOTMA-MSP-MEF. 2008. Decree No. 353/008 of 07/21/08 on
biosafety of genetically engineered plants and its parts. Amending Decrees: No. 535 of
11/03/08 and No.280 of 06/08/09.
URUGUAY. Ministry of Livestock, Agriculture and Fisheries (MGAP), Directorate of
Agricultural Statistics (DIEA). 2012. Anuario 2012.
http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,5,659,O,S,0,MNU;E;27;8;MNU;,
__________. 2012. Agricultural Survey Winter 2012. pp.1-3.
URUGUAY. National Biosafety Cabinet (GNBio). 2011. Risk Management Commission
(CGR) minutes.
__________. 2013. Applications submitted.
http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,1,620,O,S,0,,
__________ . 2013. Application form.
http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,1,619,O,S,0,,
US Environmental Protection Agency (EPA). 1998. Guidelines for ecological risk
assessment. Federal Register 63(93):26846-26924. EPA 630/R-95-002F, Washington,
DC. 188p.
US National Academy of Sciences (NAS). 2002. Environmental Effects of Transgenic Plants.
The scope and adequacy of regulation. Washington DC: National Academy Press. pp.
2-3. Available at
http://books.google.com.uy/books?hl=es&lr=&id=AL38BAoWCbMC&oi=fnd&pg=P
A1&ots=lupv2WNOiU&sig=GCrxSraHpFFX_IkDbSUlEeTpZ8Q#v=onepage&q&f=f
alse

81

US National Research Council (NRC). 1983. Risk Assessment in the Federal Government:
Managing the Process. National Academy Press, Washington, D.C.
__________. 1993. Issues in Risk Assessment. Committee on Risk Assessment
Methodology, National Research Council. National Academy Press, Washington, D.C.
__________. 1996. Understanding Risk – Informing Decisions in a Democratic Society.
Committee on Risk Assessment Methodology, National Research Council. National
Academy Press, Washington, D.C.
__________. 2002. Environmental Effects of Transgenic Plants – the Scope and Adequacy of
Regulation. Committee on Risk Assessment Methodology, National Research Council,
National Academy Press. Washington, D.C.
US Office of Science and Technology Policy (OSTP). 1986. Coordinated framework for
regulation of biotechnology: announcement of policy and notice for public comment.
Federal Register 51:23 302 - 23 393.
US Pew Initiative on Food and Biotechnology. 2007. Project homepage.
http://www.pewhealth.org/projects/pew-initiative-on-food-and-biotechnology85899367237
Weebadde CH and Maredia KM. 2011. Environmental biosafety issues associated with
genetically engineered crops. In: Grumet G, Hancock J, Maredia K and Weebaddee C.
ed. Environmental Safety of Genetically Engineered Crops. East Lansing, USA,
Michigan State University pp 21-29.
Wilson AK, Latham JR and Steinbrecher RA. 2006. Transformation-induced mutations in
transgenic plants: Analysis and biosafety implications. Biotechnology and Genetic
Engineering Reviews 23:209-234.
Wolfenbarger LL and Phifer PR. 2000. The Ecological Risks and Benefits of Genetically
Engineered Plants. S Cience´s Compass Review: Biotechnology and ecology 209:20882093.
Wolfenbarger LL and Grumet R. 2002. Executive Summary In: Proceedings of a Workshop
on Criteria for field testing of plants with engineered regulatory, metabolic, and
signaling pathways, June 3-4, 2002, Washington DC, ed. LLWolfenbarger. Blacksburg,
VA: Information Systems for Biotechnology. pp. 5-12.
Wolfenbarger LL. 2003. Annotated Bibliography on Environmental and Ecological Impacts
from Transgenic Plants I: Transgene Persistence and Gene Flow. Information Systems
for Biotechnology, Virginia Tech pp 44.
Wolt JD and Peterson RKD. 2000. Agricultural biotechnology and societal decision-making:
the role of risk analysis. AgBioForum 3(1):39-46.

82

Wolt JD, Keese P, Raybould A, Fitzpatrick JW, Burachik M, Gray A, Olin SS, Schiemann J,
Sears M and Wu F.2010. Problem formulation in the environmental risk assessment for
genetically modified plants. Transgenic Res 19:425–436.
Young BG. 2006. Changes in Herbicide Use Patterns and Production Practices Resulting
from Glyphosate-Resistant Crops. Weed Technology 20(2):301-307.

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CHAPTER II: ESTABLISHMENT AND ANALYSIS OF THE URUGUAYAN
REGULATORY SYSTEM FOR GENETICALLY ENGINEERED CROPS

INTRODUCTION
Uruguay has recently adjusted its regulatory system that controls the introduction and
use of genetically engineered crops. The objective of this chapter is to describe the
Uruguayan experience over a period of approximately two years (2009-2011) implementing
the new framework. The information presented in this chapter is based on my direct
experience as the Technical Secretariat for the Interministries Working Group, coordinating
the meetings, elaborating the group technical documents, providing bibliography and
technical reports of the topics discussed, and monitoring approved events in the region and
worldwide. I was hired and supervised by the National Division of the Environment
(DINAMA) of the Ministry of Environment. Once the Decree 353/008 was approved I was
hired by the National Agency of Research and Innovation as the coordinator for the analysis
of the risk assessment. The President of the Risk Management Commission supervised me.
This overview includes a description of the regulatory system with special emphasis
on the risk assessment phase. The general and underlying criteria used for the application of
the risk analysis methodology to the genetically engineered crop technology are also
presented to explain how the building process was guided.

HISTORICAL EVOLUTION OF THE BIOSAFETY REGULATORY FRAMEWORK
ON GENETICALLY ENGINEERED ORGANISMS IN URUGUAY
Uruguay established specific procedures to regulate the introduction and use of
genetic engineering for plants early in the development of these technologies worldwide. The
first record is from 1995, when the General Direction of Agricultural Services (DGSA) of the
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Ministry of Livestock, Agriculture and Fisheries (MGAP) issued a resolution establishing a
procedure for risk analysis following transgenic corn and Round-up Ready (RR) soybean
applications (Uruguay, 1995a,c, 1996a). An Advisory Committee for Risk Analysis (CAAR)
was composed of representatives from the Direction of Agricultural Protection (DPA) of the
MGAP, the Direction of Seeds of the MGAP – which later on was substituted by the National
Institute of Seeds (INASE) (Uruguay, 1997, 2009) - and the National Agricultural Research
Institute (INIA) (Uruguay, 1995a,c, 1996a). The authority with the final decision was the
director of DGSA of MGAP. The advisory body CAAR was a fast solution to respond to the
corn and soybean applications allowing for utilization of new technology regionally and
worldwide.
At the beginning CAAR was convened by resolution of DGSA specifically for each
application (Uruguay, 1995a, c). In January of 1996 CAAR was established permanently for
the analysis of transgenic plants (Uruguay, 1996a). The advisory committee CAAR evaluated
the applications applying the risk analysis methodology used by DPA for weeds and invasive
species (Uruguay, 1995a, 1996a). Under this framework seven events in corn, one in soybean
and two in eucalyptus were authorized for field trials. In addition, the herbicide tolerant RR
soybean with the event 40-3-2 was soon deregulated under Resolution of the DGSA-MGAP
in October 1996 (Uruguay, 1996d). A summary of all applications from the period of 19952012 including crop, event, trait, gene, year of application and authorizing agency has been
compiled in Table A2.1 (see Appendix). These early applications and the following ones
shown in Table A2.1 indicates the rapid advent of this technology to Uruguay and the need
for policymakers to define a regulatory framework.
Since the establishment of CAAR, the regulatory framework has been adjusted and
strengthened in two occasions as illustrated in Table 2.1. The first adjustment was in 2000
with the promulgation of the Decree No. 249/000 by the Ministries of Agriculture, Economy,

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Health and Environment, that established a framework with specific procedures for
genetically engineered plants (Uruguay, 2000a). The decree 249/000 created the Commission
on Risk Assessment of Genetically Engineered Plants (CERV), expanding the institutions
integrating the advisory commission and establishing new procedures (Uruguay, 2000a).
CERV was composed of representatives from the Ministry of Agriculture, Environment,
Health, INASE and INIA (Article 5 in Uruguay, 2000a). CERV based the procedure in the
risk analysis methodology (Uruguay, 2000a). The competent authority was the Ministry of
Agriculture and Economy for deregulations. DGSA was the competent authority to authorize
events for “contained use”, “field trials”, “national evaluation of cultivars”, and “seed
multiplication” (see later the explanation of these proposed uses). The Ministries of Health
and Environment had their respective authority over food safety and environment,
respectively, according to other laws and rules existing at that time.
Under the framework established by the decree No. 249/000, two events in corn,
MON810 and BT11, were deregulated for commercial use, and eight permits were issued for
field trials (Tables A2.1 and A2.3). For each deregulated event two resolutions were issued,
by MGAP-MEF and MVOTMA. The Resolution of MGAP-MEF deregulated the event itself
(MON810 or BT11) (Uruguay, 2003a, 2004b). This resolution was without biosafety
conditions, only with the requirement of an insect resistance management plan specific for
corn Lepidoptera (numeral 5, Uruguay, 2003a, 2004b).
The Resolution issued by MVOTMA established conditions to the planting of the
deregulated event (Uruguay, 2003b and Uruguay, 2004c respectively). MVOTMA’s
resolution established 250 meters as isolation distance and the planting of corn not resistant to
lepidopteran insects in 10% of the planted area operating as refuge.

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Table 2.1. Evolution of the Uruguayan regulatory framework on biosafety of genetically
engineered crops.
Resolution issued by:
Period

Framework
Authority

19952000

20002007

20072008

Resolution
DGSAMGAP
Decree No.
249/000

Decree No.
037/007

Firms

Director of DGSA

1

Ministers of MGAP and
MEF for deregulation.

Risk analysis
done by:
Advisory
Members
body
CAAR

3

2

Director of DGSA for uses
CERV
5
under controlled biosafety
1
conditions (field trials and
seed multiplication).
Suspension of the treatment of any new applications. GIM
proposed a draft decree of a new regulatory framework,
approved in July 2008 (Decree 353/008).
CGR

Decree No.
353/008

ERB

1

CAI

9

Ad Hoc
Groups

2008present

GNBio composed of the
Ministers of: MGAP, MEF,
MVOTMA, MSP, MIEM and
MRREE.

6

25-30

6

Regarding the resolutions issued for field trials, six out of eight were for events that
had been previously commercialized in other countries: BT11 (1), NK603 (2) and
MON810XNK603 (2) in corn, and LLrice62 (1) (Table A2.1). The mentioned events already
had an application in place requesting deregulation or were soon then presented. Thus, the
field trials performed were either to test the efficacy or to assess agronomic traits for the
national register of cultivars (Table A2.1). The other two resolutions authorizing field trials
were for white clover also to test efficacy, but the event was in a less advanced state of
development. This was also the situation for the events in eucalyptus authorized for field
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trials under the responsibility of the former framework. None of the events in eucalyptus and
white clover requested new permissions or reached the commercial phase.
The advisory body CERV had two periods while the decree 249/000 was in force. A
first period is distinguished from 2000 to early 2005, and the second period since then until
the promulgation of Decree 037/007 that disintegrated CERV. In the former period, CERV
consolidated its procedures and analyzed the events described in the previous paragraph
(Table A2.1). Between 2004 and 2005 it started a new wave of applications but the
momentum slowly began to stop accompanying the political transition that the country went
through in 2005.
In March 2005 a political transition period started between the guidelines and
authorities from a government that traditionally alternated between the Colorado and National
parties throughout most of Uruguay’s history, to a new government elected from the Broad
Front party - a coalition of socialists (Uruguay, 2005). Five applications entered in 2005,
with events in corn (NK603, MON810XNK603, TC1507), soybean (FG74) and rice
(LLrice62), which could not complete the risk analysis because members of CERV were
replaced when the new administration took place and CERV, suspended its work de facto (in
fact). These applications were rescinded waiting for new policy signals. Except for LLrice62
and FG74 soybean, the three events in corn re-applied under the currently regulatory system
for the same proposed uses (Table A2.1).
At the same time stakeholders were actively participating in a project that had started
in February 2004 to develop a proposal for a National Biosafety Framework (NBF) (Uruguay,
2007a). The NBF project was supported by the United Nation Program for Environment
(UNEP) and it was led by the National Division of the Environment (DINAMA) of the
Ministry of Environment (Uruguay, 2007a). The NBF project had broad participation,
gathering stakeholders under the National Committee of Coordination (CNC). The CNC had

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periodic meetings and were organized in working groups by issue: (1) research and
development of LMO, (2) biotechnology in industry, (3) administrative issues, (4)
environment, (5) socio-economic and (6) health (Uruguay, 2007a). The main criticisms to the
existing regulatory system discussed at the CNC were the low participation of scientists at the
risk analysis process and the lack of data provided by local environmental studies for risk
assessment when the events in maize MON810 and Bt11 were authorized for commercial
release (Uruguay, 2007a).
Therefore, besides the new government with a different political party, the NBF
project put the genetically engineered organisms topic in the public agenda and a climate of
tension and pressure started for a change in the existing regulatory system.
The first consequence of this transition period was a Resolution issued by the Ministry of
Environment banning the import and planting of genetically engineered sweet corn, which
has now been in force since August 2006 (Uruguay, 2006). This Resolution is based on the
powers granted by the General Environmental Protection Act No. 17283 to the Ministry of
environment in its Article 22 and 23 (Uruguay, 2000b). This Resolution was triggered by
complaints received by environmental authorities from a nongovernmental organization of
irregularities at the importation of sweet corn. The irregularities relate to an import that was
divided for sale in small bags. The small bags were not properly identified with the required
label indicating that was transgenic corn seed. Although the corn that was being sold
contained the event BT11 that had been approved for commercial release in 2004 (Uruguay,
2004b), the resolution is for all kinds of sweet corn hybrids, including those containing
authorized events such as MON810 and BT11. This resolution is discussed more thoroughly
in this chapter when issues of the current agenda are discussed (page 145).
Soon after this Resolution, in January of 2007, the second adjustment period of the
regulatory framework started with an 18 months moratorium (suspension) period imposed

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with the promulgation of the Decree No. 037/007 by the Ministries of Agriculture, Economy,
Health and Environment (Uruguay, 2007b). The Decree N° 037/2007 suspended the
treatment of any new applications for authorization. The events already deregulated, round-up
ready soybean (40-3-2 event), and the two events in corn, MON810 and Bt11, continued to be
commercialized and planted according to the respective resolutions (Uruguay, 2003a, b; 2004
b, c). During that time CERV stopped functioning formally and an interministries working
group (GIM) was convened to review and adjust the regulatory system established under the
Decree No. 249/000.
Simultaneously, the discussions at the CNC of the NBF project were tense and
nongovernmental organizations stopped participating (Uruguay, 2007a). In March 2007 the
director of the National Division of the Environment (DINAMA) gave the project completion
(stopped the project before its due date) and a final report was elaborated. The DINAMA’s
report organized the existing information at that time and compiled the recommendations
elaborated at that point by the different working groups, as well as recommendations from the
technical team of the project and the National Implementing Agency (Uruguay, 2007a).
Although not all of the proposals described in the DINAMA’s report were validated by the
competent authorities, the background information gathered and the diagnoses of the
genetically engineered organisms situation was used as starting point in the discussion at the
GIM working group. The GIM group was composed of a representative from the Ministries
of Agriculture, Environment, Health and Economy. The GIM group analyzed three scenarios
for Uruguay, 1) a regulatory system for a country free of transgenic crops, 2) a regulatory
system based on coexistence among different production systems, 3) no control over
transgenic crops. These three scenarios were analyzed from the point of view of its legal,
technical and economic feasibility (Uruguay, 2007b).

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GIM recommended to the ministers the coexistence scenario, which was approved and
they set a deadline for the submission of a regulatory system proposal. For the elaboration of
the proposal of a biosafety framework, GIM created four inter-institutional Ad Hoc groups to
analyze 1) the design of the operating structure for the regulatory framework (Institutional
Working Group – GTI for its acronym in Spanish), 2) labeling (Labeling Working Group,
GTE), 3) Public participation (Participation Working Group – GTP), and 4) legal issues
(Juristic Working Group – GTJ). GIM developed a proposal of biosafety framework, which
was approved under the Decree No. 353/008 (Uruguay, 2008). The Decree No. 353/008
revokes the Decrees No.037/007 and 249/000 and it contains the present regulatory
framework that is in force since July 2008. Decree No. 353/008 has typos amended in Decree
No. 535/008 of 11/03/08 and a modification to the addition of the possibility to charge the
applicant for the risk analysis process performed.

CURRENT REGULATORY FRAMEWORK
Criteria and characteristics of its implementation
CGR led the building process of the current regulatory system guided by a set of
criteria, some of which were taken from risk analysis methodology, and others defined by
CGR. Those criteria, summarized in Table 2.2, frame the risk analysis process and were used
to organize the description of the implementation of the current biosafety framework in
Uruguay.

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Table 2.2. General criteria of the Uruguayan biosafety framework.
Criteria

Criteria to
guide the
operation

Criteria to
guide the
decision
making

Risk Analysis
Biosafety restricted to GE plants
Process based
Risk analysis methodology
Case by case
Step by step
Iterative/independent
Open/transparent/documented
Health safety
Environmental security
Socio-economic considerations
Political considerations
Legal considerations
Commerce considerations
Monitoring/surveillance
Public confidence on framework

Risk Assessment
Case by case
Step by step
Comparative
Substantial equivalence
Familiarity

Assessment restricted to event
Scientific justified statements.
Weight-of-evidence approach

Scope. “Biosafety” restricted to GE plants
The current regulatory framework continues to include only genetically engineered
plants and its parts. At this time there is no designation of a competent authority to regulate
genetically engineered animals, microorganisms, and vaccines apart from what is established
at the environmental Act 17283, article 23. The scope of the term “biosafety” in the decree
353/008 is less comprehensive than the definition used at the Convention on Biological
Diversity (CBD) (CBD, 1992) and the Cartagena Protocol (CP) (Secretariat of the
Convention on Biological Diversity, 2000) (see Chapter 1 of this thesis) since it covers only
plants and their parts within the concept of GE organisms. The other aspects of biosafety are
taken into account under a different Uruguayan legislation. For the Decree 353/008
“biosafety” refers to a) The goal of ensuring that the development and use of genetically
engineered plants and products made from them do not negatively affect plant, animal, or
human health; genetic resources; or the environment; b) Policies and procedures adopted to

92

avoid risk to human health and safety, and to the conservation of the environment, as a result
of the use of genetically modified plants for research and commerce (Traynor et al., 2002).
The Decree No. 353/008 gives the responsibility to the authorities involved in the new
framework to elaborate a biosafety bill for genetically engineered organisms. A national
biosafety law is required to have the same legal hierarchy level as other related topics such as
the national environmental protection law, land law, and Cartagena Protocol that was recently
ratified (Uruguay, 2011). The fact of implementing a framework in parallel with the
elaboration of a biosafety bill has advantages and disadvantages. The main advantage is that
the experience generated allowed visualization of aspects necessary to be included in the law
accordant with Uruguay’s situation, as well as determining which the best mechanisms and
tools for every step of the decision making process are. The main disadvantage is the delay in
the consolidation of the system since it will mean inevitably another instance of adjustment.

Process based
The genetic engineering process utilizing recombinant DNA is what triggers the
regulatory system (Uruguay, 200). The rationale for process-based regulation is that GE
technology has a high potential to obtain new products that are morphologically and
physiologically significantly altered. It appears that it is not the technology per se, but its
potential impact that makes necessary to take a cautious attitude and determines that GE
crops follow a regulatory channel different from conventional crops. All genetically
engineered plants and their parts require an authorization to be produced and/or used in
Uruguay. Other countries, like Canada, have a product-based system (Nap et al., 2003). A
product-based approach gives coherence to the system in the sense of biosafety. For example,
technologies applied in conventional breeding such as mutagenesis, which also may result in
unexpected effects, may require a deeper analysis
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Risk analysis methodology
The current regulatory system maintains the risk analysis (RA) as the methodology for
the decision making process, as had been used under the previous framework (Uruguay,
2000a; 2008). The general principles and rationale behind the RA methodology are the basis
for the operating structure of the new framework. The main changes compared with the
previous framework (Decree 249/000) are found in the organization and institutionalization of
the official bodies and steps involved in the decision making process (Tables 2.3 and 2.5).
As described in the literature review of this thesis, the RA is an internationally
accepted methodology to determine whether to authorize the use of GE organisms (US NRC,
1996; OECD, 1993, 1995; Secretariat of the Convention on Biological Diversity, 2000;
Codex Alimentarius Commission, 2001, 2003; FAO, 2009a; EC, 2002a,b). This methodology
is broadly applied in the field of biosafety and in general for all new technology. This
methodology allows for integration of the “biosafety” concept along with policy and
regulatory frameworks (including instruments and activities) for analyzing and managing
relevant risks to human, animal and plant life and health, and associated risks to the
environment (FAO, 2007).
The RA has three independent, but highly connected components: risk assessment,
risk management and risk communication (Codex Alimentarius Commission, 2003). The
logic underneath the RA methodology explains the operating structure of the framework
established in the Decree N° 353/2008 for genetically modified organisms. Uruguay has
always based its framework for GE plants in the RA methodology. Throughout the past 15
years the number and variety of participating stakeholders has expanded (Tables 2.1 and 2.3).
The first advisory commission, CAAR, was created from the risk analysis commission
for pests. CAAR had three members from the orbit of one ministry (agriculture) and applied
the methodology for risk assessment of weeds and invasive species that was in place at that
94

time (Uruguay, 1995a,c, 1996a). The subsequent system under Decree 294/000 also applied
the risk analysis methodology but created a specific commission for risk assessment, CERV,
which was also in charge of the risk management and risk communication (Uruguay, 2000a).
CERV had five members from the orbit of three ministries (agriculture, health and
environment), and the ministry of economy participated when authorizing applications for
deregulation.
The current system under Decree 353/008 created two figures for risk assessment, the
Risk Assessment on Biosafety (ERB for its acronym in Spanish) and the Institutional
Coordination Committee (CAI); and two figures for risk management, the Uruguayan
National Biosafety Cabinet (GNBio) and the Risk Management Commission (CGR). The
institutional design of the current framework tries to reflect the conceptual distinction that the
risk analysis methodology applies between Risk Assessment, Risk Management and Risk
Communication. The areas of assessment and management are separated in different
specialized commissions and advisory bodies.
The National Biosafety Cabinet (GNBio) and the Risk Management Commission
(CGR) are the risk “managers”. The Risk Assessment on Biosafety (ERB) and the
Institutional Coordination Committee (CAI), from where Ad Hoc groups on specific areas of
concerns are formed, are the “evaluators”. Multiple strategies can be employed for risk
communication. For the time being, two mechanisms have been implemented, “inform” and
“consult”, as a requirement for each application in the decision-making process. The decree
353/008 also gives the possibility to form a Biotechnology Advisory Committee (CCB) for
consultation regarding biosafety and biotechnology policies.

95

Table 2.3. Evolution in the establishment of bodies involved in the Uruguayan regulatory
system from 1995 to present.
Framework
1995-2000
Resolution DGSAMGAP
2000-2007
Decree No. 249/000

2008-present
Decree No. 353/008

Authority
MGAP

MGAP and MEF
for deregulation.
DGSA and INASE
for contained
applications under
biosafety
conditions.
GNBIO: MGAP,
MEF, MVOTMA,
MSP, MIEM,
MRREE

Advisory
body
CAAR

CERV

CGR

ERB

CAI

Ad Hoc groups
GAHCIM
GAHFG
GAHONOB
GAHSHA

96

Integration
DGSA-MGAP
INS-MGAP
INIA
MGAP
INASE
INIA
MVOTMA
MSP

MGAP
MEF
MVOTMA
MSP
MIEM
MRREE
Specialists on biosafety
of GE plants in
environment, health and
animal issues, acting as
coordinator of the risk
assessment process.
MGAP
MVOTMA
MSP
INIA
INASE
UDELAR
LATU
IIBCE
IP
Conformed from
specialists from CAI’s
institutions.

The new framework involves twenty-two members, ten for risk assessment and twelve
for risk management, from the orbit of seven ministries (agriculture, health, environment,
economy, industry, foreign and culture), academia and research institutions (Table 2.3).
Figure 2.1 summarizes the structure in a diagram. In the diagram the risk management phase
is shown to the left and in a higher position compared with the risk assessment phase. This is
not the standard arrangement described in the risk analysis methodology where assessment
come before management, but was adopted in Uruguay to interpret the hierarchical
relationship between “managers” and “evaluators” where the formers lead the process (CGR)
and take the final decision (GNBio). This is also the reason that the application process
begins at the CGR, since CGR determines the terms of references and deadlines for the risk
assessment phase (ERB, CAI and Ad Hoc groups).
There is a clear example in rice that illustrates the rationale for beginning the
application at the CGR. After the problem experienced by the US with low-level presence of
transgenic rice in a shipment to the EU, Uruguay was able to establish a new market (EC
RASFF, 2006, 2007). The rice growers association asked the government for support to keep
the EU market, by prohibiting production of transgenic rice. This was a political decision due
to the current market. Thus, if an application for GE rice was received, the CGR may decide
not to pass it to evaluators and may directly answer that it will not be authorized due to trade
reasons. Or, the CGR may give it to evaluators even though will not be authorized, but to
save time if the market changes in the future.

97

Figure 2.1. Diagram of the operating structure of the Uruguayan biosafety framework according to Decree No. 353/008.
98

The National Biosafety Cabinet (GNBio) is the ultimate authority composed of six
Ministers: the Ministers of Agriculture, Economy, Environment, Health, Industry, and
Foreign affairs. The Ministry of Agriculture presides over the GNBio. The GNBio
responsibilities include:
-

Make the final decision of the RA process to authorize or not the requested
permissions. An authorization for any type of use requires the signature of the six
ministers.

-

Define the guidelines of the national biosafety policy of GE plants.

The Risk Management Commission (CGR) has the responsibility of implementing the
regulatory system acting as the task force and advisory body of the GNBio. CGR is
composed by a representative of each ministry of GNBio with a total of six members plus
their respective alternates. The representatives are elected directly by each minister having
their trust and professional knowledge in the subject. CGR meets twice a month at the
Ministry of Agriculture (MGAP).
The CGR responsibilities include:
-

Advise the Executive Power in terms of biosafety

-

Define the terms of references to guide the risk assessment

-

Establish a time-frame for each step of the RA process, once expired CGR should
take a decision

-

Inform GNBio of each action taken at the RA process

-

Advise the competent authority regarding risk management conditions to be
enforced

-

Manage the public participation process

-

Followed up the authorized GE plants and biosafety conditions to ensure that they
are being implemented

99

The Risk Assessment on Biosafety figure (ERB) is an advisory body of CGR that
address the assessment of the potential risk to human, animal and plant health, as well as that
of the environment, based on technical and scientifically sound arguments. ERB leads the
environmental and health risk assessment in a systematic way with all the public and nonstate public institutions with competence on the subject respectively involved at the
Institutional Coordination Committee (CAI).
ERB can be composed up to a small number (1-3) of independent scientific experts
that lead the risk assessment of genetically modified crops for health and the environment
working within a scientific network. The ERB has support for the implementation of the risk
assessment network from CAI, which is composed of head staff from nine public and nonstate public institutions respectively involved in the scientific network. ERB’s scientific
opinion is forwarded to the Risk Management Commission (CGR) that leads the risk analysis
process.
Since the implementation of this framework, I have been hired by the National
Agency of Research and Innovation (ANII) to work for GNBio-CGR at ERB. The ERB
responsibilities include:
-

Ensure a case-by-case analysis of the risk assessment performed on an objective
scientific basis.

-

Identify national and regional capacities for the multidisciplinary analysis required
for risk assessment.

-

Design protocols for environmental and health risk assessment to be adjusted case
by case,

-

Elaborate an action plan according to the terms of references received from CGR
for each application, to be used with CAI.

100

-

Promote the networking in a multidisciplinary and inter-institutional coordination
for the complementary development of skills allowing to focus on different
aspects of the risk assessment.

-

Ensure the right functioning of the network, systematically assembling the
information and interchanging it among evaluators.

-

Elaborate a final report advising CGR on the results obtained by ERB and CAI
after analyzing the risk assessment received by the applicant and/or requesting
additional experiments and additional scientific information to be reviewed during
the process.

-

Budget for performance of additional experiments, if required, and to manage the
resources assigned by CGR to ERB for the evaluation. Provide information to the
biosafety network and to the public consultation process.

-

Ensure the guarantees of the right process.

The nine institutions that form CAI are: the Ministries of Health, Environment,
Agriculture, and Education (Institute of Biological Research Clemente Estable, IIBCE),
academia (UDELAR, public University), Technological Laboratory of Uruguay (LATU),
National Institute of Agricultural Research (INIA), National Institute of Seeds (INASE),
Institute Pasteur of Montevideo (IP). The delegates of the CAI have the responsibility to
provide evaluators for the biosafety network according to the institutions’ competencies and
to maintain the flow of communication and information between ERB and evaluators. The
relationship between ERB and CAI is preceptive (mandatory) but non-binding. Thus, ERB
has to convene CAI, receive their opinions and transfer them to CGR in its final global report.
But ERB’s opinion does not necessarily have to agree with each institution of CAI. Also,
ERB does not need to wait for CAI delegate’s reports if they are not issued on time.

101

Regarding risk communication, there are two formal instances in place during the risk
analysis process: “information” and “public consultation” (Figure 1.1) (Uruguay, 200). In
Annex 1 of the application form is requested a summary of the submission that should not
include confidential information. As soon as the application enters the system Annex 1 is
made available on the web as a mechanism to “inform” the public about the events that
entered the system and are being evaluated. In the “information” mechanism comments are
not received.
The second mechanism, “public consultation”, is implemented once CGR has
performed a preliminary analysis of ERB’s final report regarding food safety and/or
environmental security. The tool used for the mechanism “public consultation” is ”to
manifest” to the public the final report of the risk assessment phase by making available at the
web site the ERB-CAI’s final report. The consultation is communicated to the public through
publishing a press in two-high circulation national newspapers during two days of high
newspaper demand. CGR assigns a period of time in which written comments are received by
the biosafety office at MGAP via electronic or paper. The duration of the public consultation
varies according to the proposed use. CGR has defined one week for applications requesting
contained uses and two weeks for deregulation.
Given the structure of the risk assessment phase with a wide participation of related
institutions in the field, it is expected that no comments are received from scientific experts
but their opinions are channeled through the Ad Hoc groups and CAI to ERB during the
analysis process. The role that the delegate of CAI plays is key to achieve that experts
interested in the matter get involved in the risk analysis. Thus, the mechanism of public
consultation is targeted to interested parties that do not participate in the risk assessment or
management phases.

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Case by case
Applications are analyzed on a case-by-case basis (Uruguay, 2008). “Case” in this
context is defined by the: 1) event (crop-gene), 2) applicant and 3) proposed use. If any of
these three changes, it is considered a different “case” and it requires its own specific
administrative file and final GNBio resolution. Note, that transfer of a given approved
transgenic event from one variety to another by conventional breeding is not subject to reevaluation by the regulatory process. Nevertheless, during the risk analysis process there are
general discussions regarding environmental risk assessment that move away from a strict
case-by-case approach and consider categories of crop-trait combinations. For example,
events in maize that confer herbicide tolerance, or events in maize that confer resistance to
Lepidopteran insects are analyzed all together at the end of the process in the risk/benefit
analysis.
An event is defined as an independent genotype derived from a transformation
experiment with a specific/unique gene integration pattern in the genome according to: the
number of copies, the location in the chromosomes and the level of integrity of the
transferred sequence. An event refers to the unique recombinant DNA inserted in one plant
cell, which was then used to generate entire transgenic plants. Every cell that successfully
incorporates the gene of interest represents a unique “event”. Every plant line derived from a
transgenic event is considered a biotech crop. The Event Names correspond to the identifiers
commonly used by regulatory authorities and international organizations, such as the
Organization for Economic Cooperation and Development (OECD).
Different proposed uses are defined from contained and controlled use, to commercial
release that means deregulation and can be used without biosafety conditions except if they
are required due to the biology of the crop or special environmental conditions. The proposed
uses considered in the Decree No. 353/008 are:

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-

“Contained” use, which include laboratory, growth chamber, greenhouse or any
other physical structure that allow to “contain” the event in it.

-

“Controlled” use, which include environmental release for:
o field trials for research purposes
o field trials for the National Register of Cultivars (NRC)
o pre-commercial seed production or seed multiplication which includes
counter season or winter seed production

-

Deregulated use which includes release for production and commercial use for
direct consumption or processing.

-

Import of GE food, feed (grains) or industrial raw material.

For the proposed use under the category “contained” CGR has planned to request the
formation of a biosafety committee at each institution or company that develops and/or uses
GE plants. The biosafety committee will be responsible for controlling the use of the GE
plant under biosafety conditions and will need to communicate to CGR each event that is
being used sending a report with its information.
The proposed use under the category “controlled” refers to the release into the
environment under biosafety conditions. The purpose of research field trials is to be able to
do risk assessment especially in the case of recently developed or events currently under
development. However under this category the applications submitted so far have been for
events already deregulated in some countries to test efficacy and/or agronomic performance.
Efficacy tests are not mandatory and it is the choice of the developer whether to apply for
testing the event under the Uruguayan specific environmental conditions. The applications
submitted under the current framework for research field trials with efficacy purposes are all
from the same company (Table A2.1).

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Field trials for NRC are field trials to evaluate agronomic characteristics of new
cultivars to be included in the National Register of Cultivars. The category “evaluation for
the National Register of Cultivars” is similar in area to an experimental field trial but it is
done by an official organization, INASE. The Act No. 16811 determines that each new
cultivar, GE or not, has to be evaluated by the official authority which will determine if it
could be incorporated to the National Register of Cultivars (INASE, 1997, 2009). This is not
a risk assessment, it is an agronomic evaluation to ensure that it is a new cultivar. Any
cultivar needs to be included in this Register in order to be commercialized in Uruguay.
INASE has standard protocols for the evaluation of agronomic traits for each crop. The field
trials are performed by INASE at two locations for two years. The data obtained is published
yearly in the web. This is a condition in order to commercialize the seed, whether GE or not,
and whether or not the GE crop was deregulated. Recently INASE has allowed
commercialising the seed after the first year of the two-year agronomic field trials (INASE,
2007). The category “evaluation for the National Register of Cultivars” allows anticipating
this agronomic evaluation before the event is deregulated. Otherwise, a GE crop after being
deregulated will require one additional year of agronomic performance to be included in the
national register of cultivars. This category of use saves time on the one hand, but on the
other it forces INASE to perform field trials under confined conditions for all cultivars with
non-authorized events. This has required INASE an statistic redesign of the field trials in
1

order to have together “non-yet authorized” events in order to save money and being able to
compare the data with new cultivars of the same crop with authorized events or nontransgenic. For example new corn hybrids with the event MON810 are required to be
evaluated by INASE, but field trials do not need to be done under confined conditions

1

“non-yet authorized” refers to events that have not yet being authorized for commercial use,
only for the field trials performed by INASE.
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because the event MON810 was deregulated in 2003 (Uruguay, 2003a). On the other hand,
corn hybrids with any event that has not yet been deregulated are required to be evaluated
under biosafety conditions until the event is deregulated.
There is another clarification necessary to include in this proposed use, related to the
process for commercial release of a new event. That an event is authorized for NRC field
trials does not necessarily mean that in one year it will be commercialized. In order to be
commercialized the event needs the specific authorization of deregulation. As it is intended to
allow agronomic evaluation of new cultivars with non-yet authorized events for commercial
use, the applicant usually applies first for NRC field trials. But the applicant may or may not
apply for deregulation. During the two years at NRC field trials the market could change and
there may be no interest of the company to sell it or the breeder may discontinue the line. On
the other hand, an event used in counter-season seed production may request deregulation in
order to avoid seed production with biosafety conditions. As long as this event is only planted
for counter-season seed production and not commercialised in Uruguay, it does not need to
be in the National Register of Cultivars. Table 2.4 lists the events submitted for review under
the current framework for the two categories, NRC and deregulation, or one of the two.
Table 2.4. Applications submitted between 2009 and 2011 by event for the two categories,
National Register of Cultivars (NRC) and deregulation, or one of the two.

1
2
3
4
5
6
7
8
9
10
11
12

Crop/Event
Corn GA21
Corn GA21XBT11
Corn TC1507
Corn NK603
Corn MON810XNK603
Corn GA21XMIR162XBT11
Corn MON89034XMON88017
Corn TC1507XNIK603
Soybean MON89788
Soybean MON89788XMON87701
Soybean A2704-12
Soybean A5547-127

Field trial NRC (c)










X
X

106

Deregulation (e)







X
X




Since the beginning of a biosafety framework in Uruguay, 16 events have been
authorized for NRC field trials, from which 11 have also requested deregulation (eight are at
the present deregulated and the other three are under evaluation) (Table A2.1). Regarding the
five events that requested NRC field trials but not deregulation, it is known that three of them
have been discontinued by the breeder (events in corn 176, T25 and CBH351) and for one
event in soybean (MON89788) the applicant lost interest to commercialise it in Uruguay
because there is a new stacked event that combines MON89788 with insect resistance
(MON87701). The other event (TC1507XNK603 in corn) may be submitted for deregulation
in the future; the application has not been pursued due to a business decision and not traderelated reasons.
The other use included in the category “controlled” is pre-commercial seed production
or seed multiplication. A kind of seed multiplication that has been successfully initiated in
Uruguay under the current regulatory system is counter seed or winter seed production.
Under the previous frameworks in the 90’s there were small areas of winter seed production
of GE-corn for France and Italy authorized under biosafety conditions (Personal
Communication, Bayce D, Manager of the Uruguayan Seed Chamber, 2011). Under the
current regulatory system winter seed production was initiated with GE-soybean. The first
year 1500 ha was planted, which was increased to about 2500 ha this past season. Winter
seed production of soybean provides the grower 4.5 times greater income than grain
production (Souto, 2010). This category necessitated the implementation of a system to
monitor the compliance of the biosafety conditions established and the traceability of the seed
from the time of import until it is exported or destroyed.
A problem within the “controlled” category has arisen from the fact that an upper
limit in area for each of the proposed uses, especially seed multiplication, is not defined.
Even though counter season seed production is done under biosafety controlled conditions, it

107

implies large areas. Environmental NGOs, the Ministry of Environment and a sector of the
public university claim that counter season seed production should be considered as
commercial release due to the big area. The risk analysis process is focused as a “field trial”
but it is argued that it should be considered under the approach used for a deregulation. This
is the case for Brazil that does not allow winter seed production unless with an event that has
been deregulated.
The inclusion of counter production under the “controlled” category is a clear political
decision related to economic and commercial opportunities. Winter seed production is a way
to realize two cycles of the crop in one year thereby obtaining more seed in less time. When
this production is required for the launch of a new event, there would not be time for a risk
analysis of the type applied for a deregulation. Instead the risk analysis performed for
“controlled” use applications is shorter since it does not include food safety analysis because
the seed will not be used for human or animal consumption in the country. Besides, the
authorization is issued season by season which allow more flexibility in case a risk was
underestimated. The official view that underlies this category is that as long as there are
enough human resources and infrastructure to monitor the compliance of the biosafety
conditions, the area allowed to plant should depend on the estimated risk level according to
the gene/trait/crop combination as well as the information and weight of evidence available at
the time of the risk analysis.
Applications for counter season seed production could apply also for deregulation.
Once deregulation is issued the expensive procedures to comply with the biosafety protocol
and its control are not required. Except for the event MON89788, the rest of the events
authorized for this category of use (MON89788XMON87701, A2704-12 and A5547-127)
had later applied for deregulation. If the events are deregulated they will neither require
applying for permission nor biosafety conditions for winter seed production. However, it will

108

be necessary to seriously consider the markets where Uruguay exports soybean grain to
determine the necessity to maintain a traceability system in order to avoid either low level
presence or adventitious presence above the import country’s thresholds. At the moment
Uruguay exports the majority of the soybean production to China and there has not yet been a
problem of this kind (Souto, 2010).
Finally, the category of use “Import of GE food, feed (grains) or industrial raw
material” refers to products of crops containing transgenic events that are imported to be
consumed as food, feed (grains) or industrial raw material. It is established in the Decree as
mandatory to apply for authorization for the import of food, feed and raw material for
processing as food or feed for events not yet deregulated in the country. This category is
important because there may not be an interest for all events to be cultivated in the country,
but they can be imported as food or feed. This use can be authorized for consumption but not
for planting. Germination capacity also can be eliminated, for example by drying the grain
with a heat treatment or breaking it in half as a way to avoid its dissemination in the
environment. Thus, it requires mainly food safety assessment while cultivation requires also a
deep environmental assessment.
This category should contemplate consumption in its broad sense including human
and animals. A split use approval for feed use but not for human consumption is not
recommended due to infrastructure limitations and difficulties for assuring that “feed only”
products remain exclusively in “feed only” marketing channels. This difficult situation was
2

demonstrated in the US with the corn line StarLinkTM (U.S. EPA, 2001; Uchtmann, 2002)
which was approved for cultivation and feed use only but was found in the human food
supply. Although there is no document evidence that the presence of StarLinkTM in human
2

OECD unique identifier: ACS-ZM004-3 (CBH-531), trade name StarLink. This corn
contains a modified cry9C gene and bar gene conferring insect resistance and herbicide
tolerance respectively.
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food caused harm to any person, it had significant economic consequences (U.S. EPA, 2001).
In this category of use that implies consumption as food and feed but not cultivation, it would
be necessary to control if there is no deviation of use mainly from feed to cultivation. This
control would imply a traceability system between the seed and grain importation and their
commercialisation.
The possibility of authorizing an event for food and/or feed but not for cultivation
implies a shorter assessment, and offers a solution to the potential problems resulting from
asynchrony in the events approved by different countries in a region. This situation can lead
to intentional or non-intentional illegal introduction from neighbour countries that already
have approved the event for cultivation. However, there are no antecedents of these kinds of
applications and at the same time there is not yet a control of the imports in this regard. In
3

general it is the seed company, which has the interest to have an event approved for the
cultivation of their varieties/hybrid containing the event. An option while the control of
imported events as food/feed is adjusted, is for the government itself (“from the official
sector”) to apply for food safety assessment of events that could be imported as food/feed.
The goal would be to achieve approval for human and animal consumption. This could be
coordinated with the regulatory authorities of the other countries of the region and with the
companies that own the event and had performed the food safety analysis in order to obtain
the necessary information.

Step by step
Figure 2.2 outlines the steps followed from 1 to 9 by an application for the RA
process. (1) The application form (see Table A2.2 in the Appendix) is formal delivery to the
3

For an event to be cultivated not only requires environmental studies but also the agreement
of the owner of the event for its planting in relation to the intellectual property.
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Biosafety Office at the Ministry of Agriculture. My assignments included drafting of the
form to be in compliance with the new guidelines. As inputs I used the final document of a
workshop organized by FAO which had the objective to develop regional consensual criteria
for the basis of decision-making on biosafety. In the agenda was included the discussion of
the criteria and parameters to be included in the application form. This workshop was part of
a regional project regarding the development of technical tools to be used as reference in
biosafety by regulators of the expanded MERCOSUR countries i.e. Argentina, Brazil,
Paraguay, Uruguay, Chile, Ecuador and Bolivia (FAO, 2009b). I participated in this
Workshop as one of the Uruguayan regulatory system representatives. I also reviewed other
systems currently in place in the US, Canada, EU, New Zealand, Australia, Mexico and
Japan. The draft was made available on the website for public consultation. Uruguay
emphasized inclusion of the ecosystem for the risk assessment and not only the agro
ecosystem. It also requires information and data specifically to evaluate the feasibility of
coexistence, and includes a section in the form requesting information for a risk/benefit
analysis which would contribute in part to socioeconomic consideration. Particular attention
was put in each area of concern to request information and data needed by a regulator to
characterize potential risks and to be able to formulate a hypothesis risk if additional tests are
required.
As the system became operational, adjustments to the application form were
necessary. For instance, adjustments were made to the required information for the different
categories of uses and for the information required for each area of concern. The dynamic
nature of the biotech crop sector determines adjustments to be a continuous process.

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Figure 2.2. Diagram of the operating structure of the Uruguayan biosafety framework according to Decree No. 353/008 with steps followed by
an application for the risk analysis process.
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ERB does a first analysis of the application to summarize to CGR the information
provided in section I of the form. Section I includes general information of the applicant, the
event, the trait it confers, the mechanism of action of the gene, the proposed use and countries
where the event has been already authorized (Uruguay, 2009).
(2) CGR defines the terms of references case by case for the risk assessment. The terms of
references provide a guide for the analysis performed by evaluators. The evaluators are then
responsible to perform a strict analysis of biosafety aspects directly related to the event under
consideration. The terms of references also include any concerns that CGR feels are required
for special emphasis in the study. For example in the case of events in corn, CGR called for
special emphasis on the study of management practices and measures to ensure coexistence.
In the case of winter seed production, based on the results or changes in area planted
compared with a previous season, CGR may request the adjustment of specific conditions of
the protocol that are required for technical recommendation from evaluators. In the terms of
references, CGR also sets deadlines for CAI and ERB submission of final reports and
deadlines for each process. The terms of references are communicated to ERB. At the same
time CGR publishes on its homepage (http://www.mgap.gub.uy (enter at “Biosafety
Cabinet”) a summary of each application so that citizens know what is being analyzed in the
system.
(3) ERB coordinates with the biosafety network through CAI the analysis of the risk
assessment provided by the applicant in the dossier.
(4) ERB compiles the Ad Hoc groups and CAI reports in a global final report regarding food
and environment safety that is submitted to CGR.
(5) CGR performs a first analysis taking into account the technical/scientific ERB/CAI
report, a socio-economic report requested to the Office of Agricultural Planning and Policy
(OPYPA) of MGAP and introduces other political and commerce factors.

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(6) CGR implements a period for public consultation during which the ERB/CAI report is
available on the Web and comments are received at the Biosafety Office. CGR analyses and
responds to comments. Technical or scientific considerations are transferred to ERB for its
analysis.
(7) CGR elaborates a recommendation report to GNBio taking into account the report by
ERB/CAI on environmental security and food safety, the report by OPYPA on socioeconomic aspects, the comments received during the public consultation period, as well as
other factors that include, political, legal and commercial considerations, whichever is
applicable.
(8) GNBio takes the final decision. If it is an application for commercial release, the Ministry
of agriculture convenes the GNBio for the analysis of the events under consideration.
Applications for uses under biosafety controlled conditions are analyzed without a face to
face meeting.
(9) Once GNBio has taken a final decision, CGR communicates it to the applicant and to the
civil society. The resolution is notified to the applicant and then it becomes available at the
website for the civil society.

Iterative but independent
Risk analysis is performed in an iterative process that implies a permanent interaction
between risk managers and risk assessors. ERB serves as a link between the two phases. On
the other hand, while this interaction is necessary for a practical application of the risk
analysis, it is essential to keep a functional separation of risk assessment and risk
management to ensure the scientific integrity of the risk assessment analysis recommended
by the Codex Alimentarius (2007). CGR has put forth a strong emphasis to avoid
contaminating risk assessors with issues of risk managers and conversely. Members of CGR
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can neither be members of CAI or Ad Hoc groups nor participate in the meetings of risk
assessors. In the same way, ERB participates at CGR’s meetings by the iterative condition of
the process but ERB leaves the room when CGR discuses a final recommendation. This has
been a practical mechanism applied by CGR to prevent confusion over the functions to be
performed by risk assessors and risk managers reducing any conflict of interest.

Open, transparent and documented
An open, transparent and documented process is the baseline set forth by the risk
analysis methodology. Everything is required by the risk analysis process to be documented
fully in a transparent manner indicating different opinions with their respective justifications
and how a final decision was reached. Information and reports are available to interested
parties at the Biosafety Office, as well as the applicant. Legitimate justified confidentiality is
strictly preserved. This criterion has to do with the members of the different commissions
with regard to the independence of interests involved.

Risk Assessment phase
Strictly speaking evaluators do not perform a “risk assessment”. The ideal situation to
instill confidence by the public would be that governments individually or regionally perform
the risk assessment experiments. However this is too expensive and this role has been
transferred to the applicant, which usually is a large company with economic resources to
face them. Applicants in turn, send much of their evaluations to standardized laboratories that
are established as meeting requirements for good regulatory practices with referencing.
Applicants also often make agreement with research institutes to perform field trials as a way
to build confidence in the data generated. Thus, evaluators from the government analyze the
information and data that the applicant submits. In the case of Uruguay, as a “technology
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taker” country, evaluators also analyze data collected on the GE plant in the country of origin
and/or other countries where the event was already authorized. A common confusion
regarding the role of experts as regulators is to believe that tests and analyses provided by the
applicant have to be repeated by the regulatory system. However, the function of the
evaluator is, by using his expertise, to verify the results in order to validate or not the
analyses.
The criteria discussed later in this section frame the analysis that evaluators perform
on the risk assessment presented by the applicant. The risk assessment phase was organized
to facilitate efficient use of human and infrastructure resources, and to prevent duplication of
efforts while working in a multidisciplinary and inter-institutional scientific network.
ERB leads the risk assessment phase coordinating the analysis performed for each
event with the biosafety network through CAI and Ad Hoc groups. The number of evaluators
that comprise the biosafety network varies between 25 and 30. ERB has generated Ad Hoc
groups to organize the biosafety networking. The Ad Hoc Groups are formed with evaluators
from the institutions that form CAI. The aspects addressed by the Ad Hoc groups are 1)
molecular characterization and identification of the event, 2) gene flow and coexistence, 3)
non-target organisms and 4) human and animal health. Their acronyms in Spanish are
respectively GAHCIM, GAHFG, GAHONOB and GAHSHA.
Functions undertaken by ERB include:
-

Promote broad and active participation at CAI and Ad Hoc groups to avoid
conflicts after a decision is taken

-

Provide clear explanations to each institutional authority regarding the key
function of the delegate at CAI, who must be qualified and have some authority.

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-

Promote an open environment for discussion at the Ad Hoc Groups where
evaluators can offer their independent opinion. CAI can include in its report the
institutional opinion.

-

Elaborate consensus documents on specific topics by the Ad Hoc groups. in order
to move forward and avoid wasting time disusing the same topic.

-

Enforce deadlines for meetings and reports.

-

Keep all discussion on a scientific basis.

-

Ask for clear terms of references from CGR.

-

Keep a transparent and documented interaction with CGR and CAI

-

Explain clearly to the evaluator its function. As regulators do not perform the
research, they need to verify information, determine if there are studies that need
to be repeated locally due to a different receiving environments, or if new studies
are required. The experimental design must be based on a risk hypothesis to aid
the decision making process, not for the purpose of increasing scientific
knowledge per se.

As mentioned before, some of the criteria applied to analyze the risk assessment, are
principles of the risk analysis methodology itself, such as using a case-by-case, step-by-step
and comparative approach based on the concepts of familiarity and substantial equivalence
(Table 2.2). Other criteria are defined by CGR, such as the requirement to center the analysis
on the event and not on issues related to the associated technology package (e.g., agronomic
practices), or to require the analysis of stacked events, even though the individual events have
been already deregulated, or that local efficacy studies are not a requirement. The next
paragraphs expand on aspects of the operating structure of the Uruguayan biosafety
framework according to Decree No. 353/008 relative to these criteria.

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Scope
The analysis performed by ERB, CAI and Ah Hoc groups has clear boundaries set by
CGR to focus on the event and not on issues related to the associated technology package.
These issues refer to aspects such as no tillage technology, the impact on soil conservation
due to monoculture of soybean, the impact of agrochemicals use, or generation of herbicide
resistance. Specific divisions at the Ministry of Agriculture and Environment have
responsibility for these aspects. Notwithstanding what is mentioned above, evaluators have
recommended to CGR to create an additional Ad Hoc group on issues associated with the
technology package.
Instead of a permanent Ad Hoc group, the recommendation was channeled by CGR
through a pilot mechanism consisted of a meeting with the directors of the Natural
Renewable Resources (RENARE) of MGAP (with responsibility on soil conservation and
Good Agricultural Practices (GAP) plans), and the director of DGSA of MGAP (with
responsibility on the registration and use of agrochemicals), with the President of GNBio
(Minister of Agriculture who convenes the meeting), the president of CGR, and ERB’s
coordinator. The meeting holds at MGAP among RENARE, DGSA, GNBio and CGR
presidents and ERB, was conducted as part of the risk analysis process of five events in corn
that were recently deregulated with insect and herbicide resistance. The main focus was on
the fact that an eventual deregulation of additional crops with glyphosate tolerance would
necessarily determine an increase in the use of glyphosate, with the possible consequence of
generating resistance. As a result it was determined, that in addition to recommendations for
management practices for soil conservation that RENARE will include in its GPA policy,
consideration of the appropriate crop rotations to avoid generation of resistance to the
herbicides glyphosate and glufosinate ammonium. This mechanism must be formalized in the
CGR statutes adding to be able to include directors from the Ministry of Environment as

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appropriate. This meeting among authorities from MGAP and the regulatory system would be
made when CGR considers it necessary, with the main objective to keep a fluid horizontal
communication among the divisions of the Ministries involved in the matter to articulate and
coordinate the agricultural policies.

Case by case
In the Decree 353/008 it is determined that the complex interplay of factors to
consider determines the necessity to organize the assessment of potential impacts on a caseby-case basis according to the specific intended conditions of use. In this process “a case” is
defined by: 1) the type of the plant (species/crop), 2) the gene, 3) the trait and 4) the
environment where is going to be released, interacting as shown in Figure 2.3. While CGR
can move away from a strict case-by-case approach and consider categories of crop-trait
combinations, ERB, CAI and Ad Hoc groups require a strict case-by-case analysis for each
defined area of concern.
For example, evaluators require, in the context of gene flow risk, verifying whether
the reproductive biology of GE plants has been altered as a result of the introduction of a
genetically engineered-derived trait compared to conventional corn. The review of the
reproductive biology information provided by the applicant has to be done for each particular
event separately, although the gene and the conferred trait under consideration could be the
same, such as the case of MON810 and BT11 in corn or A2704-12 and A5547-127 in
soybean. An event is an independent genotype derived from a transformation experiment
with a specific/unique gene integration pattern in the genome. The situation is different for
“managers” in that once “evaluators” have characterized on a case-by-case basis a nonsignificant risk related to gene flow, CGR can consider categories of crop-trait combinations

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such as corn with insect resistance or soybean with herbicide tolerance, to define, for
example, measures for feasibility of coexistence and for measures to avoid insect or herbicide
resistance.

gene

trait
crop
location
Figure 2.3. Environmental safety considerations for GE crops result from a complex interplay
of factors that vary with crop, gene, trait, and location. (Figure from Grumet et al., 2011).

In the case of GE plants containing stacked events, i.e. where more than one event is
introduced by conventional crossing of lines containing the single events, a risk assessment is
required even though the individual events have been already deregulated. Possible effects of
the combination on the biology and/or reproductive characteristics of the GE plant are
specifically compared with the single events, following the European Union approach (EFSA
2007; 2011a). The analysis focuses on the stability of the stacked inserts and potential
synergistic or antagonistic effects between the gene products of the stacked events that could
raise safety concerns. The first stacked event submitted for permission in Uruguay was in
2003. Corn with the events MON810XNK603 was authorized for field trials (Table A2.1).
Under the current regulatory framework, six out of nine applications of events in corn are
stacked while one out of four in soybean are stacked (Table A2.1).
In addition to stacking traits by conventional crossing of two or more transgenic lines,
genes can also be combined in the original transformation construct. These are single events
but with two or more genes in the inserted cassette that confers different traits, such as insect
resistance and herbicide tolerance. There are also cases of single events containing more than
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one gene for the same trait (e.g., multiple insect resistance genes) transformed with a
multiple-gene cassette. Three of nine events in corn reviewed by the current regulatory
system have a single event with a multiple-gene cassette (TC1507, MON89034 and
MON88017) (Table A2.1). In some cases, the gene that confers herbicide tolerance is also
used as a marker gene. Interestingly two of these stacked events, BT11 and TC1507, were
submitted to the previous regulatory system in 2003 and 2005, respectively (Table A2.1), but
were treated as insect resistance single events (Uruguay, 2004b,c). Only now in their recent
application, the applicant promotes the herbicide tolerance gene, which was indicated in the
previous application as a marker gene, as a second trait because that herbicide is now
registered in Uruguay.
Under the current regulatory system the more complex cases so far are the stacked
events GA21XMIR162XBT11 and MON89034XMON88017. The former has three single
events stacked by conventional breeding with a total of four genes (mepsps X Vip3Aa20 X
Cry1Ab, pat) conferring two traits (resistance to certain insects of the same family conferred
by two different genes (Vip3Aa20 from MIR162 and Cry1Ab from BT11), and tolerance to
two different herbicides conferred by the other two genes (mepsps from GA21 and pat from
BT11). In the case of the event MON89034XMON88017, it has two single events stacked by
conventional breeding with a total of four genes (Cry1A.105, Cry2Ab2 X Cry3Bb1, cp4
epsps) that confer two traits (resistance to certain insects, in this case from different families
conferred by three different genes (Cry1A.105 and Cry2Ab2 from MON89034 for
Lepidoptera and Cry3Bb1 from MON88017 for Coleoptera), and tolerance to one herbicide
conferred by the gene cp4 epsps from MON88017) (Table A2.1).

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Step by step
The RA methodology proposes to follow a series of steps to be applied in risk assessment
for each area of concern (Hill, 2005; Johnson et al., 2006; Craig et al., 2008; EFSA, 2010a)
The application form requires information and data that is used by evaluators to follow the
following sequence of steps.
7) Identification of potential adverse effects, which will depend on the specific
combination of crop-gene-trait and receiving environment.
8) Estimation of the probability of occurrence of those adverse effects identified, which
is related to the exposure level (e.g., field trial vs commercial release).
9) Evaluation of the consequences (impact assessment) if those adverse effects occur.
10) Characterization of the risk combining the probability of occurrence (2) by its
consequences (3). Risk = probability X consequences
11) Consideration of possible adequate strategies for the management of the risk
characterized, which could reduce the probability of occurrence and/or its
consequences and to meet contingencies.
12) Estimation of the global impact including possible positive effects, namely
risk/benefit balance.

Comparative analysis based on familiarity and substantial equivalence
The current regulatory system accepts the approach for the risk assessment that
includes the use of the concepts of familiarity (FAO, 2009a) and substantial equivalence
(FAO, 1996, 2000; Codex Alimentaruis, 2003). A comparative approach is employed, since
substantial equivalence is determined by comparative analysis of the GE plant with its
conventional counterpart, which has a long and well-established history of safe use, i.e. it is
“familiar”. One of the most important aspects of risk assessment is the identification of
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intended and unintended differences and equivalences between the GE plant and its
comparators. This comparison requires an appropriate comparator and robust baseline
information to take into account the range of natural variation (Codex Alimentaruis, 2003;
EFSA, 2011a).
The current regulatory framework has not yet defined a specific requirement for
comparators. There is an ongoing discussion by ERB with evaluators regarding which lines
should be the conventional counterpart for comparison due to the difficulty in obtaining nonGE lines with comparable genetic background. So far, the comparators are either isogenic
lines in the case of vegetative propagated crops, or non-GE lines as close as possible
genetically to the GE plant under assessment in the case of sexually propagated crops (EU
Directive 2001/18/EC; EU Regulation (EC) No. 1829/2003). However, these comparators are
not always available due to the increasing complexity of events when traits are stacked or
those in which the trait implies significant compositional changes.
The current regulatory system needs to incorporate a flexible approach according to
the situation. The GMO Panel of EFSA has recently published a guidance with options for
the selection of comparators recognizing also a different requirement for comparators for the
different aspects analyzed at the risk assessment phase (molecular characterization, food/feed
safety and environmental security) (EFSA, 2011a).
It is also necessary to take into account the range of natural variation among current
cultivars, and whether changes in the transgenic line fall within or outside that range (EFSA,
2011a). For this reason, non-GE commercial varieties are also included in the comparative
assessment to provide a reference range for phenotypic and ecological characteristic values
common to the crop under consideration.

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Analysis guided by areas of concerns
Evaluators identify possible adverse effects (step 1) from general areas of concerns.
The areas of concerns that Uruguay includes in the application form are aligned with the ones
proposed by the US, EU, countries of the region (FAO, 2009b) and in general by all countries
with a regulatory system in place. The areas of concern included in the Uruguayan
application form are summarized in Table A2.2 located at the end of this chapter. The
identification of the general areas of concern is discussed more thoroughly in chapter 4 of this
thesis.
The major topic areas to be evaluated are molecular characterization, food and feed
safety and environmental security, referred in the first column as “terms of references” like it
is expressed in CGR’s convocation. Until now food/feed safety has been evaluated only in
applications for deregulation. In the short term it is expected to start being evaluated for
events under the category of use “import of GE food, feed (grains) or industrial raw material”
in which case food/feed safety would be the main assessment and environmental security
would be included to be covered as a preventive measure in case of release into the
environment due to deviation of use. In the other columns are shown the specific information
needed for each topic area. The application form requests the information in a way to allow
evaluators to characterize the risk and complete the steps mentioned above regarding each
area of concern.
Molecular characterization includes evaluation of the genetic elements inserted, the
products from those elements expressed in the GE plant and genetic stability of the insertion
(Uruguay, 2009). The description of the inserted genetic elements is considered important
because it provides the number of integration sites and number of copies of the gene as well
as whether there also was insertion of portions of genes. The regulator looks for stable events
preferentially with only one insertion site, one copy of the gene and without portions of genes

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inserted in other parts of the genome or rearrangements inside the insert as well as absence of
new open reading frames.
In the case these things happen, the regulator reviews molecular and bioinformatic
analyses to confirm that additional copies or portion of the gene are not functional, or there is
no transcription and translation from new ORF, or the protein expressed is not functional and
does not have homology with allergenic or toxic molecules. If a scientifically justified
concern (risk hypothesis) arises, more information or additional studies are requested to the
applicant.
Food safety evaluation includes mainly history of use and familiarity of the GE plant,
substantial equivalence of the GE plant compared with its conventional counterpart in terms
of nutritional composition, digestibility of the GE protein, pathogenicity, allergenicity and
toxicity in mammals, as well as carcinogenic and teratology studies if required (Uruguay,
2009). The criterion defined and being used by CGR is to base the decision-making regarding
food safety on EFSA’s risk assessment and risk analysis performed at the European Union
(see as example GNBio resolution 27, Uruguay, 2011). The main constraint in this regard is
the lack of experts with capabilities and training as evaluators to analyze the GE food safety
assessment provided by the applicant. There are specialists on nutritional aspects but they do
not have the training of what to look for as regulator. Specialists from the area of health in
allergenicity and toxicology have clinical knowledge based on observation of the patient,
while for risk analysis are needed specialists on the molecular biology aspects of the protein.
Institutional support in this regard is a requisite before the criteria applied by CGR could
change and for Uruguay to be able to complete the analysis of food safety information
provided by the applicant.
Environmental assessment includes the analysis of the biology of the receiving
organism, the resulting GE plant, and the receiving environment. The characterization of the

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receiving organism (homolog) is important for the regulator to determine if there could be
compatible wild relatives, if the crop species present features characteristic of invasive
species or weed as well as to determine the feasibility of coexistence according to its
reproductive biology (Hancock, 2003). While coexistence is not a biosafety issue, as
explained later in this chapter, it could be included in the terms of references indicated by
CGR to evaluators, in order to recommend management measures and production conditions
to ensure coexistence. The characterization of the genetically engineered plant is important to
determine if there are any changes in the biology of the plant as a consequence of the genetic
modification compared with its homolog, that could allow the crop to be produced in new
environments and if so, if the crop could become invasive or a weed and/or could cause a
change in gene flow pattern that could affect coexistence conditions (Hancock, 2003).
Finally, the characterization of the receiving environment is important to determine
whether there are compatible wild relatives in the region where the crop is going to be
planted (Ellstrand, 2003; Hancock, 2003). However, the existence of compatible relatives
does not mean that the event would not be authorized. The situation of corn in Mexico is a
clear example in which although the characterization of the receiving organism determined
that there are compatible relatives, the characterization of the receiving environment allowed
to define areas free of compatible relatives where research field trials are being conducted
(Ortíz, 2011). The characterization of the receiving environment is also important to
determine if the gene/trait introduced could confer a selective advantage that could influence
wild populations as well as if could occur non-target impacts of the new trait (Ellstrand and
Hoffman, 1990; Snow and Palma, 1997; Hancock, 2003). In the characterization of the
receiving environment is where the nuances of a more ecological vs agroecological approach
are emphasized.

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Hierarchical decision tree and Weight of evidence
Field-generated data, molecular characterization data, compositional analysis and
ecotoxicological testings already generated are gathered in the dossier according to the
Uruguayan form. Uruguay indicates areas of concerns that the applicant has to provide data
in the form, but does not propose how to assess them. In this process, evaluators led by ERB,
analyze case-by-case the events going step-by-step, following a hierarchical decision tree in
which the areas of concerns discussed above are the starting point.
A weight-of-evidence approach (EFSA, 2010a,b, 2011b; Codex Alimentarius, 2009)
is validated by the current regulatory system to support assessment conclusions. For each
defined potential area of concern, evaluators perform a review of the dossier to analyze how
the studies were performed by the applicant with respect to their statistical and study design,
comparator, treatments and receiving environment in order to validate the results. Thus, it is
important for the applicant to send much of their evaluations to be performed by standardized
laboratories that meet good regulatory practices.
Additional studies performed locally
Additional studies and/or experiments could be asked of the applicant if the data are
not valid and sufficient for the Uruguayan situation/condition. This could be the case for
environmental areas of concerns if there are uncertainties with respect to a characterized risk
that require locally field-generated data to answer them. This is usually not the case for
human and animal health where molecular characterization and compositional studies are
more standardized and natural variation is lower. The criteria to require additional studies in
the context of risk assessment is to aid decision making, not to increase scientific knowledge
per se (Hill and Sendashonga, 2003; Romeis et al, 2009). Additional studies need a risk
hypothesis justifying the requirement. It is ERB’s responsibility to orient the analysis not to
completely understand a natural process but to help in the decision making process. The
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baseline argumentation is used by evaluators to define the necessity of additional local
studies is discussed below.
Persistence and invasiveness of the GM plant or its compatible relatives
The environmental areas of concern of persistence and invasiveness of the GM plant
or its compatible relatives could raise uncertainty if there are in Uruguay compatible relatives
that are not present in the environment where the studies were performed. If no compatible
relatives are present and data from comparative analyses show no differences assuming an
environment similar to the receiving environment, the probability of the event to increase the
persistence and invasiveness of the GM plant itself in our environment will be low, and will
not require additional local field studies. It is also possible to monitor this concern in a
monitoring plan.
Interaction of the GE plant with non-target organisms.
In the case of interaction of the GE plant with non-target organisms, the species and
relevant functional groups selected for this risk assessment usually are valid for our agro
ecosystem, if not, additional experiments would be required. A higher chance is the
requirement of new data for risk assessment of non-target organisms characteristic of our
ecosystem/biodiversity.
A problem that is faced by Uruguay, is that it does not have the laboratory
infrastructure that is required (Personal Communication Ing. Agr. PhD Castiglioni E. and Ing.
Agr. PhD Scattoni B, Plant Protection Department, School of Agronomy -UDELAR, 2011)
for a tiered framework approach, such as the one used to assess the environmental impact of
conventional chemical plant protection products (García-Alonso et al., 2006; Rose, 2007;
Romeis et al., 2008, 2011). The rationale behind the “early-tier” studies is to conduct
experiments under worst-case exposure conditions increasing the likelihood of detecting

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adverse effects on non-target organisms. Indicator species of non-target organisms are
exposed to concentrations of the protein under evaluation in large excess of exposure that
would be experienced in the field. If under this extreme conditions there is no adverse effects,
the risk can be characterized as being acceptable, since in the field the non-target organisms
would be exposed to much lower concentration of the toxin (Romeis et al., 2010).
A possibility is to test the impact directly in field trials which is considered as
“higher-tier” studies in the tiered framework discussed before that include semi-open field
tests under controlled conditions (contained) and open field tests. Romeis et al., (2010)
indicate that higher-tier tests demand higher skills and greater resources for their design,
execution, and analysis. Results from open field tests may be more difficult to interpret in
order to contribute with confidence in the conclusion of the risk assessment (Romeis et al.,
2010). This discussion is just starting in Uruguay among entomologists. In the short term it is
proposed to include possible indicator species and functional groups in a monitoring plan,
while adjusting the methodology recommended by the regulatory system to the applicant in
those cases where risk assessment is required for different species than the ones the applicant
already has tested.
Efficacy studies
It has been recommended by Uruguayan evaluators that the regulatory system should
require two seasons of efficacy studies (e.g., impact of the event on target organisms for
insect resistance or herbicide tolerance traits) performed locally before its commercial release
(Uruguay, 2009). Variation in environmental conditions could determine that although an
insect species is present in the tested agro-ecosystem, it may not occur at a sufficient level to
be economically important. On the contrary, an event may have low impact on a species
because it has low density in the agro-ecosystem of one country, but may provide efficient
control when the species is at high density in another agro-ecosystem.
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This latter situation was the case of the event MON810 and BT11 in corn for Uruguay
(Zerbino and Castiglioni, 2005-2010). Those events produce the Cry1Ab protein that
controls Diatraea saccharalis. D. saccaralis was not as important a pest as were Spodoptera
frugiperda and Heliotis for the Uruguayan conditions. Monitoring results shows that the
Cry1Ac protein controlled efficiently Spodoptera and Heliotis, both species not originally
indicated as the main target pests. In recent years drier conditions resulted in increased
population density of D. saccaralis, the initial intended target species. Thus efficacy will
depend on the prevailing pest in the receiving environment (Castiglioni and Zerbino, 20052009). If efficacy studies had performed, there would have been available suitable data in
which to base the regulatory decision avoiding tension at the time of its authorization.
Efficacy studies do not answer biosafety uncertainties. Their purpose is to verify the
impact of the event on the intended target organisms. The requirement of local efficacy
studies is defined politically. In the case of Uruguay there is a political definition to promote
this technology as long as there is “an acceptable risk level” and it solves a problem for the
Uruguayan production system, environment, health and/or socioeconomic situation. This
intention implies consideration of the efficacy of the regulated product. However efficacy
studies are not mandatory under the Uruguayan regulatory system.
The rationale of the evaluator’s recommendation to require efficacy testing is based
on the prevention of the introduction of unimportant or inefficacious technologies to society
(Falck-Zepeda and Zambrano, 2011). This would necessitate that efficacy studies be
performed locally to verify three things: 1) that the declared target organisms are
economically important pests in the agro-ecosystem of Uruguay, 2) that the event has a real
effect on the declared target organism in the agro-ecosystem of Uruguay, and 3) if the event
has impact on other target organisms not declared but with economic importance in the agroecosystem of Uruguay.

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On the other hand, Uruguay does not require demonstration of improved agronomic
qualities prior to introduction of new cultivars, whether they are transgenic or non-transgenic.
This is in accordance with the World Trade Organization (WTO) directives, to which
Uruguay is member since 1995. According to the policy trade, the only reasons to prevent the
commercialization would be due to phytosanitary (WTO) reasons or environmental risk
(Environmental Protection Law). This implies that the introduction of new cultivars/hybrids
with a lower agronomic performance than presently used is not forbidden. The agronomic
performance is publicly documented and it is available at the INASE website for new
cultivars/hybrids of the majority of the crops (INASE website, 2013). The information and
data published derive from the field trials for the National Register of Cultivars mentioned
above. In the context of efficacy studies for transgenic crops, this would imply that a negative
result would not be a condition to prevent its introduction if there is no risk for the
environment and health.
In the case efficacy studies become required a third party such as academia, the
National Agriculture Research Institute (INIA) or the National Institute of Seeds (INASE), is
recommended to perform the efficacy studies. One possibility could be to adjust the statistic
design of INASE’s field trials for NRC in a way that includes efficacy data.
Even though efficacy studies are not included in the terms of references when CGR
convenes ERB and CAI to analyze the risk assessment, evaluators have repeatedly
recommended requiring their performance locally. CGR has channeled this recommendation
through the inclusion of efficacy studies as one of the projects of the plan that CGR has of
implementing biosafety research lines co-financed between CGR and the National Agency of
Research and Innovation. The intention of CGR is to contribute to the trial costs with the fee
it receives from applicants for the submissions. This proposition has been accepted by
GNBio and is currently being negotiated with the research agency. Besides, applicants have

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requested permission for field trials to determine agronomic performance in the receiving
environment and efficacy studies. GNBio has authorized these field trials performed by INIA
and a private company. The resolution issued requires including the comparator in order to
obtain useful data for comparison analysis. Applicants have interest in agronomic and
efficacy field trials to determine whether it is worthwhile to apply for deregulation and if so,
to save time by providing local data.

Underlying criteria applied in the establishment of the Uruguayan biosafety framework
While the general criteria, concepts and issues discussed so far explain the operation
of the Uruguayan biosafety framework and the risk analysis process, other underlying
principles, some of them implied, though not directly expressed or written, were essential in
the building process. Here I examine some of the factors that I believe, based on my
observations and participation in the development process, were important for establishment
of the current regulatory system. It is my opinion that the criteria discussed below allowed
regulators to take advantage of the opportunity to amend the former framework where
necessary and consolidate the current regulatory system contributing to the progressive
evolution of the Uruguayan regulatory policy toward biotechnology.
The primary programmatic guideline of the Uruguayan government to construct the
current regulatory framework was to start from integration, articulation and participation
among the different stakeholders and institutions with capacities and responsibilities relevant
to genetically engineered plants. The new structure is being built using already established
and functioning institutions. Instead of creating new official bodies there has been a real
effort being promoted by the authorities leading the implementation process, to use the
institutions, agencies and offices, that already exist in an efficient way (Uruguay, 2007b).
Under the Decree 037/007 GIM discussed within the institutional working group (GTI),
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which of the institutions were needed and justified their participation in the system (Uruguay,
2007c).
At the risk management level, the Ministries of Agriculture, Environment, Economy
and Health have a direct impact in the decision making process for the cultivation and
consumption of GE plants and/or their parts. These four ministries were the ones that
participated in the elaboration of the decree 353/008. The Ministry of Foreign relationships
was included due to the international agreements for which Uruguay is a member. The
Ministry of Industry was also included thinking forward to the inclusion in the future
National Biosafety Law of all GE organisms apart from plants and possible development of
Uruguay’s own GE products. At the risk assessment level, the nine institutions involved in
CAI were identified for having technical competence to assist in the analysis.
In the same way that integration and participation is sought, it is intended to avoid
overlap of responsibilities. An example is the control of the biosafety conditions imposed by
GNBio for seed multiplication. CGR is responsible for the monitoring and compliance
control for which coordinates with INASE and DGSA of MGAP. In this coordination there is
a permanent interagency effort of articulation and coordinated approach in order to avoid
duplications and overlapping responsibilities among different authorities. DGSA is the
authority at the points of entrance and exit of the seed because there is a DGSA’s office at
every possible port of entrance and exit of the seed either by air, sea or land.
A strong emphasis is being put forth by the president and members of CGR to assure
harmonious interaction to submit coordinated work to the ministers they represent at the
National Biosafety Cabinet (GNBio). The six ministries at the GNBio represent the
involvement in the GE technology of agriculture, environment, health, economy, industry and
foreign relationships. The goal is not to think individually regarding the competence of each
ministry but globally for the interests of the country. A fluent communication has to be

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maintained among the President of CGR with the rest of the delegates at the commission, and
they in turn have a close relationship with the Minister that they represent. It is expected that
the commission will reach a consolidated opinion including all considerations in a unique
resolution.
The previous consideration of ensuring a good relationship among system members is
connected to the necessity to have written, legally correct, procedures at each step of the
process. Working groups are composed of members who can be frequently substituted.
Clearly defined procedures will allow for a more durable regulatory system by providing
continuity and reducing the possible influence of subjectivism. The objective is to define a
regulatory system adjusted to the general programmatic objectives of Uruguay in such a way
that its operation is independent of political parties.
Regarding the risk communication process, the objective is not a change in position
but the mutual understanding between regulators and stakeholders (FAO, 2007). To achieve
this, it is necessary to explain the reasons behind the decision making and not simply provide
announcements from authorities or a description of acts. At the same time it is important that
everyone understands the mechanism of public consultation, including the role of each part,
and what public consultation does not imply. A common misconception is to believe that
authorities will take the actions suggested in comments. But, “risk managers”, which have
the responsibility for the decision-making, will consider the opinions by analysing and
reviewing the concepts implicit in the comments, decide whether or not they agree with
suggestions received, and then decide which actions will be taken. Under the current
regulatory system it is CGR that analyses the comments and responds, explaining the reasons
for the decisions taken in each aspect.
The previous framework also had a mechanism of public consultation for risk
communication. Apart from the tool of “made manifest” (documents are released for public

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consultation on biosafety office homepage for a period of time in which stakeholders are
invited to submit written comments), there was also used the tool of “public hearing” in
which interested parties meet with regulators. However the previous framework experienced
acts of physical and verbal aggression directed by the public to the applicant and regulators
during the public hearing set for the risk analysis process of MON810 deregulation (Uruguay,
2003a). The “public hearing” process carried out was not successful partly due to the
transition period the country was going through on this matter. But also, the public was not
warned in advance that the purpose of the public hearing was to collect stakeholders’ views
on the matter, and not an instance for discussion, reproach or decision making. Under the
current framework CGR has given special attention to the process of risk communication.
A feature of the Uruguayan risk communication process is that only the result of the
risk assessment analysis (ERB-CAI’s final report) is presented to the public requesting
comments. CGR’s report is confidential until GNBio’s resolution is published; it is then
included as part of GNBio’s resolution. If both documents were presented to the public more
focused comments were expected on specific aspects of the CGR’s recommendation to the
Ministers. The reason of this approach is not explicitly established. While holding CGR’s
recommendation report as confidential could appear as insecurity by the “managers”, in so
far that this approach has been consolidated, it is more efficient for CGR to have all the
opinions for elaborating the final recommendation included in the CGR´s report to the
Ministers.
With regard to transparency, this concept goes beyond the goal that everyone has
access to information and is informed about the systematic process as it was done.
Transparency also refers to a mechanism to reach a final decision without conflicts among
stakeholders. In order to achieve an effective and efficient final resolution, transparency in
this sense has to be applied from the beginning of the process. CGR promoted awareness and

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was clear in its explanation to interested parties regarding the function and responsibilities of
risk assessors and risk managers in the Uruguayan regulatory policy and specifically in the
risk analysis process. CGR has been clear in explaining that “risk zero” does not exist and
risk managers make the final decision assuming a risk level. ERB and CGR has taken special
time to explain to interested parties about the procedures followed to reach each of the
decisions taken along the process that led to the final recommendation to GNBio. To the
degree practicable, CGR and ERB met both with companies and with NGO explaining
factually the uncertainties and constraints as well as the premises and assumptions on which
the assumed levels of uncertainty and risk were based.
Another strong guideline, set forth from the early stages of elaboration of Decree
353/008 by the authorities under decree 037/007, was to decide norms according to what is
justified in aspects strictly pertaining to biosafety and what is possible to control. There has
been a real effort to avoid unreasonable rules and ideal procedures only possible to comply
with on paper. A clear example is the decision taken regarding labeling. Permission to use
voluntary labeling indicating whether a product is GE or not was established in Decree
353/008 for those foods in which presence or absence of the relevant DNA or protein can be
proven by analysis of the final product (Uruguay, 2008). The Working Group on labeling
(GTE) under GIM, recommended voluntary labeling instead of mandatory labeling, and
product based labeling instead of process based labeling, because it was determined that it
would not be affordable by the government to comply with the control implied by mandatory
labeling and even less for process based labeling (Uruguay, 2007d). Mandatory labeling
requires controlling the whole row of products that are not GE to verify that they are not GE.
Voluntary labeling puts the onus of controlling all products that are labeled either as “GE”
product or as “not GE” product on the producer and marketer of the product.

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The same criterion is applied when an event is approved subjected to conditions
imposed by GNBio. CGR took the precaution to be sure that the system has the capacity to
assure that the conditions are actually being met post-approval. In the case of counter season
seed production, that is a new category of use in Uruguay and there was not certainty of its
permanence. CGR had to define a legal framework for the control of the biosafety conditions
to be imposed by GNBio. CGR used INASE’s legal backing to control certified quality seed
production in Uruguay to be the official inspection agency. INASE had already a traceability
system in place for the seed from the time of import until its harvest and commercialization.
CGR added to the traceability system the responsibility to ensure compliance of the Biosafety
protocol. This explains the additional condition of certified quality seed production applied in
counter season seed production category although customers do not require certified quality.
By requiring certified quality, CGR found the legal way that INASE is the official inspection
agency to oversee biosafety conditions. Additionally GNBio requires the applicant to present
to CGR the reports of an external audit.
This last example is also applicable to the criteria discussed above regarding
interagency efforts for a coordinated approach by integrating and articulating responsibilities.
It is the objective to build a system with predictability so the applicant can organize its work.
Due dates are established for each step by CGR and after completing the risk analysis process
an answer is returned to the applicant in a reasonable timeframe. The definition of deadlines
had a process of adjustments to ensure enough time for each step as appropriate. However, to
achieve a predictable system CGR strictly requires that deadlines are met. This is possible in
part by the fact that the relationship of dependency between ERB and CAI is prescriptive but
not binding. This means that ERB has to convene and ask CAI’s opinion (this is mandatory);
however, ERB not only can have a different opinion from CAI, but also cannot wait for
CAI’s report if the deadline expired (ERB has its own deadline to meet).

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At the risk assessment level, from the beginning of the formation of the Ad Hoc
working groups that were composed with specialists from different institutions, ERB
explained the importance of preserving the technical and scientific baseline for the
discussion. Every opinion must be technically and/or scientifically justified in order to be
taken into account by ERB with the final opinion that is elevated to CGR. This criterion is
essential when defining additional information to request to the applicant as well as defining
additional local studies. It is ERB’s responsibility to elevate a report to CGR in those terms.
The specialists selected from each institution need to have the right skills and
competencies. Where a gap of human resources exists, external specialists can be consulted
by ERB. In each institution it is desired to establish the right structure and hierarchy by
having a delegate at CAI that are expert in the topic and has a high position to be able to
name experts for the Ad Hoc working groups.
The participation in the working groups is a non-paid activity. Thus it is important to
institutionalize the task of risk assessment in the institution in order for the evaluators to find
the time for it and be recognized for this work. To obtain a prioritization of this task at each
institution is a current weakness of the system. If this is not obtained, there is no motivation
for participation, no generation of time for this task, and it will lose relevance. The option to
pay a fee for each dossier analyzed would be a motivation to increase participation. Another
suggestion was to raise awareness at the National Agency of Research and Innovation (ANII)
where scientists are voluntarily ranked at the National System of Researches (SNI) and
receive a supplement of the salary according to the level reached. For being at SNI the
participation at the risk assessment process would be a moral duty.
Soon after the entry into force of the decree 353/008, CGR decided to charge a fee for
the risk analysis in order to obtain money to co-finance national research on biosafety. This
adjustment involved changes in the original text that were approved in the Decree 535/008

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(Uruguay, 2008b). The creation of research projects on biosafety of GE crops is being
negotiated with the National Agency of Research and Innovation (ANII) for its
implementation (Uruguay, 2011).

Issues of the current agenda
Approach for the regulation of coexistence
The recently defined policy expressed in Decree 353/008 promotes the coexistence
between the production system that uses GE crops and those that do not use GE crops
(conventional, organic, landraces) (Uruguay, 200). There is not yet a regulation with norms
establishing specifically the nature of the relationship between the authority and growers to
guarantee coexistence. CGR, however, which is responsible for the elaboration of a
recommendation to GNBio in this respect, has been discussing a norm for coexistence in the
context of the risk analysis of the events in corn recently deregulated (Table A2.1). The main
ideas that are being discussed by technicians and politicians are discussed below.
It is important to clarify that “coexistence” is not a biosafety issue, but instead refers
to the fact that different production systems (conventional, organic and transgenic) should be
able to exist together at the same time. Coexistence should not be treated as if it were an
environmental or health-related risk. The product itself, whether it be organic, conventional
or transgenic, must be produced in correspondence with appropriate food safety requirements
and environmental safety.
Environmental biosafety issues include the potential loss of biodiversity, the
probability of the GE plant to become an invasive species or weed, the potential negative
impact on other non-target organisms (Table A2.2). The existence of compatible relatives as
part of the country’s biodiversity and a GE plant mechanism for gene flow that determines
transgenic introgression would be a biosafety issue assessed during the risk assessment phase.
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According to the Uruguayan legislation, introgression would be considered a potential loss of
biodiversity (Environmental Protection Act No. 17283, 2000) and therefore would be
analyzed during the biosafety risk assessment phase. The feasibility of coexistence is a
second, independent analysis, subjected to the finding of an acceptable environmental and
food safety risk level.
Coexistence concerns agronomic, commercial and economic risks. It refers to the
potential economic loss and impact of the admixture of non-GM with GM crops or the
opposite. Thus, “regulated coexistence” refers to a regulatory system in which coexistence is
guaranteed by implementing management measures and production conditions in order to
avoid the unintended presence of GMO in conventional and/or organic crops by gene flow or
admixtures. These measures are determined according to a list of agronomic, natural and
crop-specific factors in the context of specific local, national and regional conditions (ECoB,
2010). Specific regulation for coexistence would avoid lawsuits and judges determining
biosafety measures by themselves instead of baseing the decision on appropriate legislation.
Coexistence is a complex issue that has been discussed since the beginning of the
Uruguayan regulatory policy passing from one commission to another without a specific
policy. When the two events in corn, MON810 and BT11, were deregulated under the
previous framework (Uruguay, 2003a, 2004b), the Ministry of Environment issued separate
Resolutions for each event establishing conditions for their planting (“planting conditions”
hereinafter) (Uruguay, 2003b, 2004c). Among those conditions was the requirement of 250
meters as isolation distance from other non-GE corn plantations that could be considered as a
measure to ensure coexistence between different production systems. However, these
resolutions were not justified in terms of coexistence but rather in terms of biosafety issues
(Uruguay, 2003b, 2004c). Later on a draft of coexistence policy was elaborated by CERV

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(Uruguay, 2005), but not enacted, as the commission stopped working by that time as
explained in first section of this chapter.
Coexistence gained strength in the current regulatory system where it is explicitly
stated in the second preliminary statement of the Decree 353/008 “that is of (political)
interest to promote a policy of coexistence between GE plants and unmodified ones”
(Uruguay, 200).
The discussion on coexistence restarted in the framework of the risk analysis of the
five recently deregulated GE corn events (Table A2.1) (Uruguay, 2011a-e). Two of them are
stacked events that include the single event MON810 or BT11, both deregulated under the
previous framework (Uruguay 2003a, 2004b). A conflict was generated by the fact that
MON810 and BT11 had additionally a specific resolution with conditions for their planting
as explained above (Uruguay 2003b, 2004c). The arguments and procedures established in
those conditions were put forward by CGR for analysis resulting in two Resolutions issued by
GNBio (Uruguay, 2011 f, g) that modifies old resolutions in order to harmonize regulations.
The arguments of the planting conditions and the present approach are discussed more
thoroughly below.
The conditions set forth for planting MON810 and BT11 corn included: a) the
requirement of 250 meters as isolation distance from other non-GE corn plantations; b) the
planting of corn susceptible to lepidopteran insects in 10% of the area planted operating as
refuge; c) affidavits of commercial transactions with the seed; d) affidavits of planting with
information regarding area planted and a sketch of the location of the refuge (Uruguay 2003b,
2004c). The arguments provided for these conditions were based on biosafety issues
generating confusion regarding the distinction between biosafety/biodiversity issues and
agronomic issues such as coexistence and resistance management. The Ministry of
Environment issued the resolutions supporting them on the General Environmental Protection

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4

Act No. 17283 (Uruguay, 2000). This Act has a special provision for biosafety establishing
that the Ministry of Environment is competent if no authority has been designated, for the
regulation of GMO or when the introduction could be risky for the biological diversity or the
environment. The confusion arises from the fact that there was an authority designed for the
regulation of GE plants, CERV (Uruguay, 2000); it has been debated that there is no
significant risk for the biological diversity or the environment with the introduction of these
events in corn (Uruguay, 2011).
The resolutions refer to the responsibility of the Ministry of Environment of
“conservation and sustainable use of biological diversity”. However, in the case of Uruguay
the risk of cross-pollination between GE corn with compatible relatives is negligible since
Uruguay is not the center of origin of maize and there are no compatible relatives (Burkarta,
1969; Rosengurtt et al., 1970; Zuloaga et al., 1994; Speroni, 2010). Landraces instead could
be an issue in the framework of conservation of biological diversity due to their adaptation to
the local environment and valuable genetic diversity. Local varieties were not mentioned in
those resolutions and there has never been a norm to protect them neither from conventional
hybrids nor from GE hybrids. Landraces will be discussed later in this section. On the other
hand, if as a result of the environmental risk assessment a biodiversity risk is determined,
isolation distances could be a measure to mitigate the risk. But in the absence of such risk, the
isolation distance becomes a measure to address coexistence.

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Article 23 of the General Law of Environmental Protection Act No. 17283 gives powers to
the Ministry of environment “to apply the necessary measures to prevent and control
environmental risks derived from the creation, handling, use or release of genetically
engineered organisms as a result of biotechnology applications, as might affect the
conservation and sustainable use of the biological diversity and the environment”. It also
gives powers to the Ministry of environment to act in case of risks “derived from these
activities but related to human health, industrial and occupational safety, laboratory good
practices and pharmaceutical and food use”.
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The coexistence approach that is starting to be applied under the current regulatory
system is based in the following baseline information: a) The majority of the agricultural
production in soybean and corn is currently transgenic. It is estimated that 100% of the
soybean and between 60-90% of the corn planted is transgenic (MGAP-OPYPA, 2011); b)
There is no registration at the DGSA-MGAP database of certified organic producers; c) It is
estimated about 3-5% of the production systems would require coexistence accommodations
(MGAP- OPYPA, 2011); d) Since the first authorized event in corn for commercial release in
2003 there have not been complaints regarding contamination with GE corn; e) there are
alternative/complementary measures to isolation distance to attend coexistence.
Based on the above statements, instead of requiring isolation distance as a coexistence
measure to all growers that use GE corn, the current policy seeks to apply a case-by-case
approach focusing on situations that justify the necessity of coexistence accommodation.
It is expected to be less the requirement of official control in a case-by-case approach than if
imposing general coexistence measures in all cases as planting conditions established. Under
the current approach any request for regulation of coexistence has to be put into consideration
by CGR which will determine case-by-case the conditions and management required.
By this, Uruguay is applying a subsidiarity-based approach on coexistence as Europe
has (EU, 2009), but while in Europe the minority is transgenic production system, in Uruguay
the minority is non-transgenic production system and so the control is limited to specific
cases that demonstrates the necessity of isolation. Possible scenarios requesting regulation of
coexistence include: commercial issues (organic or conventional producers that needs to
certify their production as free of GE), biodiversity issues (growers that use landraces),
political reasons (supported by the Land Law). Philosophic reasons (freedom to choose) will
not be considered as no health, environmental, or economic risks are associated.

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Landraces
Local varieties could be considered as part of the biological diversity of Uruguay due
to their adaptation to the local environment and valuable genetic diversity. It is being debated
in the Ad Hoc Group of gene flow and coexistence (GHAFG) whether the impact of GE
crops must be evaluated apart from non-GE conventional corn varieties and hybrids as a
biosafety issue of the environmental risk assessment, or either GE or non-GE commercial
varieties must be considered together in the risk assessment and in the national protection
system of plant genetic resources. The later should be the situation if the risk from GE crops
on landraces were the same as would be from non-GE conventional corn hybrids (Bellon and
Berthaud, 2004). The environmental risk assessment would define if the trait conferred by the
transgene requires different, complementary or additional measures to the ones applied for
conventional corn hybrids. On the other hand, it is the possibility that non-GE conventional
corn hybrids and varieties would not cause a negative impact in the development of the
evolution of a local variety (Bellon and Brush, 1994; Bellon et al., 2003; Louette et al., 1997;
Perales et al., 2003). In this case the issue would be addressed from the regulatory system
focused on the trait conferred by the transgene.
The information regarding landraces in Uruguay is scarce and partial. There are few
records with location of local varieties with confirmed identity (Vidal, 2011). Lately the
value of local varieties is being re-considered by the Uruguayan society. NGOs and specific
family farmers are involved in promoting the conservation of landraces. But local varieties
from other countries have also been introduced recently, generating confusion regarding their
identity as landraces (Personal Communication, Ing. Agr. Vidal R., Assistant in Plant
Breeding, School of Agronomy, 2011). The regulatory system recognizes the value of
landraces as a genetic resource of Uruguay, but considers it is necessary to gather information
from credible and reliable sources. While the baseline information is being generated to

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determine if local varieties should have the same precautions with conventional corn hybrids
than with GE corn hybrids, the current regulatory system has defined to consider landraces as
another production system that need coexistence accommodation.
Adventitious presence
Adventitious presence for transgenic crops refers to the accidental, unintended,
presence by gene flow or admixtures of low amounts of the product under consideration with
an event approved in the country. Low-level presence refers to the special case of
adventitious presence in which the event has not yet been authorized in the country (Codex
Alimentarius, 2003; Demeke et al., 2006; Brookes, 2008; McCammon, 2010). Management
measures and production conditions to ensure coexistence are correlated to adventitious
presence threshold. Uruguay has just started the discussion of adventitious presence to define
thresholds. In the case of grains, Uruguay would need to set threshold values if it had a
mandatory labeling and/or if countries to which Uruguay exports grain define a threshold as a
requirement for the import of grain. Uruguay should seek to harmonize thresholds at the
regional level (Uruguay, 2010).
Prohibition of sweet corn
MVOTMA’s resolution banning the use of sweet corn, even if it has deregulated
events, is justified in accordance with Article 22 of the General Law of Environmental
Protection Act No. 17283 referring to biodiversity. As mentioned above, under the
Uruguayan environment the risk to biodiversity of the deregulated GE corn is negligible.
However, the sweet corn resolution also indicates that the environmental authority (at that
time) considered that the planting conditions for MON810 and BT11 of 250 m “are not
applicable to the technological and productive situation of the family farmers at the

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horticultural sector” characterized by small properties with plots planted adjacent one from
each other (Uruguay, 2006).
This argument relates to coexistence but it has been debated that there are other
measures to avoid contamination at the horticultural sector if plots are close that do not allow
250 m as absolute distance between crops. Such other measures include intermediate barriers
with another crop (e.g. sorghum) or rows of the non-transgenic crop to trap pollen, as well as
mismatch in the timing of planting or the use of hybrids with different crop cycle to avoid
overlap in the pollination stage (EC, 2009).
The sweet corn ban was appealed by the Uruguayan Chamber of Seeds (CUS, 2006),
but rescinded after receiving no answer from the Ministry of Environment. In case the
resolution were repealed, under the current coexistence approach GE sweet corn could be
produced and cases of non-GE sweet corn would be considered to require coexistence
accommodation. In the present agenda of the regulatory system this topic is pending a
specific revision of arguments and procedures.
Insect resistance management
Insect resistance management is another issue of the agenda linked to the planting
conditions discussed above. The condition of planting a 10% of the area as refuge was
included in the main resolution issued by MEF and MGAP for deregulation of MON810 and
BT11 in the Insect Management Plan requirement. Repeating the requirement of a “refuge”
by an environmental authority with the argument of conservation of biological diversity
generated the misconception that in the “refuge” insects will be kept in an undisrupted
ecosystem. However, the refuge area is controlled chemically against pests, theoretically
except to the target insects (CUS, 2003). The refuge addresses the agronomic concern of
insect resistance for which the main objective is to avoid generation of resistance to maintain

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the technology. The benefit of the “refuge” on non-target insect population will depend on
the target insect trophic chain.
Under the current framework it was discussed whether the control of the refuge
compliance that is being done by INASE and MVOTMA, should be transferred to the
stakeholder as is done in Brazil. However, at this time CGR has maintained the requirement
for an Insect Management Plan that includes the refuge while considering analysis of the
benefit that refuges provide for non-target species.
Monitoring/Surveillance
Another condition established for the planting of MON810 and BT11 corn (Uruguay
2003b, 2004c) was the necessity to monitoring after commercial release. This could have
been a valid biosafety assumption at that time as these were relatively new events worldwide,
and there was a lack of environmental data from plantings at a bigger scale than field trials. It
was discussed under the current regulatory framework that to address the unknown impact on
the environment at a larger scale should be applied a monitoring plan (Uruguay, 2011).
Distinction of Uruguay as “Natural Country”
The planting conditions discussed above also refer to the objective of maintaining
Uruguay with the distinction as a “Natural Country”. The use of this distinction as an
argument is not clear, since there is no legal definition of what is a “Natural Country”. This
distinction was promoted in the context of beef production and exports related to the natural
way beef production is developed in Uruguay. However, it does not say that animals cannot
eat transgenic feed. It also makes no allusion to GE crops.

147

SUMMARY OF THE PROGRESSIVE EVOLUTION OF THE URUGUAYAN
REGULATORY SYSTEM
Evolution of the basic components of a biosafety framework
In this section is summarized the evolution of the Uruguayan regulatory system
regarding two aspects, the main structural components required for a biosafety framework
and the dynamic respecting the number of application forms received, the categories of uses,
crops, traits, genes and events analyzed.
According to the program of the United Nations for the building of National Biosafety
Frameworks in the context of the Cartagena Protocol, there are five basic components
required for the structure of a biosafety framework (Ortíz, 2011). These components include:
1) Politics on biotechnology security;
2) Legal support for a regulatory regime;
3) Operational system to handle applications;
4) Operational system for follow-up actions of monitoring, surveillance and inspection;
5) Public awareness and participation.
The components listed above have been addressed in this chapter from different points of
view and will be used in this section to summarize where the Uruguay system stands and
what is needed to continue moving forward.
Looking at the evolution of the Uruguayan regulatory system on GE plants, a clear
consolidation has occurred regarding the first component listed, politics in support of
biotechnology. Biotechnology is considered by the Planning and Budget Office of the
Presidency as a key sector for the economy of the country (OPP, 2009). In addition to the
creation of the National Biosafety Cabinet specifically for GE plants (Uruguay, 200), the
Production Cabinet launched a Tripartite Sectoral Council in Bio and Nanotechnology as a
tool for articulating and generating inputs for this area (Production Cabinet, 2010). This
148

Council has recently published the Biotechnology Sectoral Plan for the period 2011-2020
(Production Cabinet, 2011).
The second component listed above, legal support, is solidly based on Decree 353/008
and is slowly progressing to a law that covers not only plants but also GE animals and
microorganisms. The main constraint in this regard is the lack of experts with capabilities and
training as evaluators to analyze the GE food safety assessment provided by the applicant. A
draft bill has been discussed by CGR parallel to the risk analysis process of the corn events
that have been recently deregulated. Aware of the situation regarding capabilities for food
safety assessment, the bill discussion process has proceeded at a laggard pace and is pending
a solution to the food safety issue. A possibility is to extend the criterion being used by CGR
for GE plants as explained earlier, by basing the decision-making regarding food safety, on
EFSA’s risk assessment and risk analysis performed at the European Union (Uruguay, 2011).
The third component, the operational system to handle applications, includes an
administrative system which supports the risk analysis phases of risk assessment and
management for decision-making and information handling. The Uruguayan operational
system has been strengthened in terms of capacities involved in the decision making process
since its origin in 1995 (Table 2.1). The main difference between the current regulatory
system compared to the previous frameworks, is the greater participation both in the political
commission of risk management and the risk assessment phase. In the period from 1995 to
2000 authorizations required the signature of 1 Minister (Agriculture), either for field trials or
deregulation. In the second phase of the regulatory system from 2000 to 2007, the advisory
body CERV issued permissions for contained use and the signature of two Ministers was
required for deregulation (Agriculture and Economy). From 2008 to present the signature of
six Ministers (Agriculture, Economy, Environment, Health, Industry and Foreign Affairs) is
required for all uses except the “Contained” category that include any physical structure. In

149

the same way the advisory bodies increased in number of members, from 3 in the first period
(1995-2000), to 5 members in the previous system to 16 (plus 25-30 evaluators at the Ad Hoc
groups) in the present system in which there is a broad participation of institutions with
competence in the subject.
This strengthening in capacities meant an increase in complexity regarding
coordination. However the current regulatory system was instituted to allow broad
participation and with a structure that includes public awareness, the fifth component of the
list mentioned above. The higher complexity was needed in order to guarantee the maximum
participation in the risk analysis phases to accomplish a decision making that is solid
scientifically and considers all the concerns of interested parties.
Another important difference from previous frameworks is the clear separation
established between the technical/scientific phase of the risk analysis from the risk
management phase in which the discussion is at a technical/political level. This consideration
and the above mentioned contribute to a transparent process and in turn facilitate noncontroversial decision making.
On the other hand, signatures from the six GNBio ministers are necessary for all uses.
A review of procedures for confined field trials is required. . Field trials for research and
cultivar registration are small (less than one hectare), and confined with biosafety controlled
conditions. For these cases would be desirable to enable CGR to issue the permits. In addition
to this, it is necessary to adjust the application form to the different categories (i.e. confined
field trial vs. commercial release) because with newer events, the applicant would likely be
able to provide less information in the application form. In the cases where trials are
performed to test efficacy or agronomic performance with events that have already been
deregulated in other countries, the applicant will likely have the required risk assessment
information. However, for new events under development, a key point of the confined field

150

trials is to obtain the information needed to perform a risk assessment. Regarding the fourth
component, an operational system for follow-up actions of monitoring, surveillance and
inspection, there have been actions for specific categories of uses on demand, such as counter
season seed production and research field trials. These actions have been isolated but oriented
toward an integrated and systematic scheme. The system is being based in INASE as the
official agency for inspection and external audit. It is necessary to consolidate this operational
system by formalizing in CGR the procedures and member’s responsibilities in the
monitoring of approved events and conditions imposed by GNBio.
As mentioned above the current regulatory system has a clear space for risk
communication. This phase of the risk analysis is still under development and adjustments of
procedures but there are already two systematic mechanisms in place, information and public
consultation, as an inclusive action done from the government. Aspects for improvement
include the mechanism by which it is reported the beginning of a public consultation period
and the duration of the consultation. The instances generated in the current regulatory system
between CGR-ERB and NGOs, helped to understand the answer to the comments received
during the public consultation, previous to its publication on the web. Similar instances
between CGR-ERB and applicants helped to understand information provided in the
application form, additional information required, as well as decisions taken. These instances
of face-to-face communication arose under the current framework as isolated and specific
actions but would be desirable to incorporate the possibility of generating these instances
when considered necessary into the risk analysis process in a systematic way. Additionally
the framework needs to make the system known to citizens and reinforce risk communication
with staff with the capacity to maintain an updated web site, to classify the comments
received, to elaborate the response, and to clarify as needed when confusing issues are
published in the national, regional and international media.

151

Analysis of applications received by the evolving Uruguayan regulatory system
The evolution of the regulatory system can also be observed with respect to the
number of application forms received, the categories of uses, crops, traits, genes and events
analyzed. These factors are summarized in Table A2.3 by the periods that the Uruguayan
regulatory system went through since its origin in 1995 until present. The tendencies that
stand out from the information provided in each column of Table A2.3 are discussed below.
In recent years there has been a decrease in the variability of plant species submitted
for evaluation. Although the number of years in the two periods mentioned is not equal (12 vs
3), in the early stages of the Uruguayan framework there were applications with less
traditional GE plant species, i.e. eucalyptus and rice submitted by the private sector , and
white clover by the public sector. Under the current regulatory system the applications have
been for the more common GE crops, corn and soybean. This tendency is also observed in the
traits analyzed. In the previous frameworks both traditional and non-traditional traits, such as
low lignin content and delayed senescence, were handled. It would be expected that as the
new framework becomes more established that a greater variety of crops and traits will be
submitted for review.
The decrease in the variability of plant species and traits submitted between 2005 and
2008 could be attributed to the transition period between different administrations and the
18-month moratorium that ended in 2008. The fact that the new government was from a
different political party resulted in a change in the politics on biotechnology. Companies
would not risk the investment without policy support and a biosafety framework. Also, the
18-month moratorium delayed the evaluation of events that were approved in other countries
in the region. Thus, on one hand the significant change in the government led companies to
take a cautious attitude toward the new regulatory system, resulting in the submission of

152

events with common crop-trait combinations that were already approved in neighbor
countries.
However, in the number of stacked traits, the trend is in the opposite direction when
comparing the previous periods with the current framework. It is observed an increase in the
number of applications with stacked events from 3 applications to 20 applications submitted
in a period of three years. This increase in the number of stacked events coincides with the
global trend (ISAAA, 2011) of pyramiding genes in a same plant to confer more than one
trait and/or to provide more than one mechanisms of action to avoid the generation of
resistance.
With regard to insect resistance there has been an increase in the variability of genes
used to confer the resistance, i.e., from 3 genes (cry1Ab, cry9c and cry1Fa2) used during the
first ten years of the regulatory system, between 1995 and 2005, to 7 genes (cry1Ab, cry1Fa2,
cry1A105, cry1Ac, Vip3Ab20, cry2Ab2 and cry3Bb1) in two years period since 2009. This
variability is not observed for herbicide tolerance trait in which the number of genes used
remains constant at 3 (epsps, bar and pat).
Regarding the number of events, corn continues to be the crop with the largest number
of applications per event. In the entire period of the regulatory system from 1995 to present
there have been 16 events submitted in corn out of a total of 27 (59%), while in soybean there
have been 6 events applied out of 27 (22%).
Respecting the proposed uses, the categories remained the same along the evolution of
the regulatory system, although the current regulatory system has added the category of use
“counter season seed production”. The establishment of such production in Uruguay, which
implies biosafety and traceability conditions applied in large areas and big volumes of seed,
is a successful experience of the framework in regard to coordination and teamwork between
the public and private sector.

153

At the moment soybean is the only crop that has been submitted for winter seed
production although there is also interest in corn. The first applications are for soybean
because it is easier to handle as it is primarily self-pollinating, and there are no compatible
relatives or local varieties in the Uruguayan environment. Submission of “easier” events may
assist implementation and consolidation.
A detail of the number of application forms entered by category of use since the
beginning of the current regulatory system is shown in Figure 2.4. Counter season seed
production is the only category that increased the number of applications per year. The
number of applications for the other categories, either have decreased after a peak in the first
year, such as field trials for cultivar registration (c) and deregulation (e), or had a peak in the
second year of the system and then decreased as occurred with research field trials (b).
The fact that in the first year of the new framework there were no applications for the
category of use research field trial (b), could be also attributed to the situation explained
above, including a new administration and prior 18-month moratorium. The applications
submitted to date do not include risk assessment tests, but only efficacy and agronomic
performance trials for events in advanced development for whichrisk assessments data have
already been generated. Efficacy tests under the Uruguayan environment are not mandatory
and could be the reason there have not been applications for (b) category. The applications
were submitted entirely by one company (Table A2.1).
The fact that there was no application submitted for cultivar registration (c) in 2011
could indicate that all available events with potential interest to be grown in Uruguay were
already submitted.

154

Figure 2.4. Number of application forms entered into the system by category of use between
2009 and august of 2011 (bars) and total number of applications per year (black line).

The dynamic observed in the total number of submissions per year, 13 applications in
2009, 18 applications in 2010 and 11 applications in 2011, is translated globally in a peak of
application forms. This dynamic of submissions is also observed in previous periods of the
regulatory system (Table A2.3) characterizing it by “waves” that went through the regulatory
system since its origin. In Figure 2.5 are represented these “waves” of submissions. The
curve in gray shows the actual number of applications entered into the system by year. The
curve in black is the rolling-3 year average. The Uruguayan regulatory system has evolved
over the past 17 years accompanied by fluctuations in the number of applications submitted.

155

Figure 2.5. Scheme of the evolution of the number of application forms entered by year and
by period of the regulatory system.
The first “wave” of events concentrated between 1996 and 1998. This tendency was
followed by a period from 1999 to 2001 with no submissions (Tables 2.2 and 2.8). The
reason for this variation could be the normal tendency in the flux of submissions that varies
for different factors, including commercial competition, availability of new products, time
required to meet official requirements previous to the commercialization of an approved

156

event, and efforts to facilitate regional coordination. That time period also included an
adjustment in the regulatory system with the promulgation of the Decree 249/000 that created
the advisory body CERV. Adjustments to the regulatory systems could imply a period of
inactivity for the applicant to analyze the changes and reevaluate the interest in applying.
However in the case of Decree 249/000 changes gave structure to the system and
consolidation of procedures.
The second “wave” of applications, was concentrated between the years 2002 and
2005, (Tables A2.1 andA 2.3). This time the abrupt decrease in the number of applications
resulted from election of a new government in 2005 that was from a different political party.
There was a complete change in the members of the review committee. Applications that
were submitted in 2005 either were not completed or were not forwarded to enter the risk
analysis process. Then the Decree 037/007 of the 18-month moratorium formalized the
inactivity of the regulatory system.
Since current regulatory system entered into force in July 2008 under Decree 353/008,
once again there has been an increase in applications (Figure 2.4), reaching the highest
number since its origin. In the first five years of the regulatory system, between 1995 and
2000, there were a total of 13 applications (2.6 applications per year). In the following seven
years (2000-2007) there were a total of 17 applications (2.4 applications per year) and under
the current regulatory system covering only three years (2008-present), there has been a total
of 46 applications (15.3 applications per year) (Table A2.3).

157

Summary and future directions
In summary, the current regulatory system needs to continue implementing the legal
aspects of the framework, moving from a decree for GE plants to a law for GE organisms
including animals, microorganisms and vaccines. The framework needs to further
consolidate its operational structure for risk analysis and post-release surveillance. In this
regard it is necessary to keep working toward a systematic and methodical administration
with order and planning in a systemic way considering the entire system’s components. It is
necessary to strengthen the technology applied and capabilities for the risk assessment phase
in order to handle the greater number of events and higher complexity in the combination of
genes/traits-crops-environments that are expected in the near future.
From a longer term perspective, Uruguay may also generate national transgenic
products. The Biotechnology Sectoral Plan for the period 2011-2020 recently published,
provides criteria on the promotion of the inclusion of biotechnology, including strengthening
of the academia-industry bridge, support for public-private partnerships, and identifications
of niches and emerging markets for Uruguayan bio-business. This will require field trials for
risk assessment, which design and parameters evaluated (chapter 4 of this thesis) would be
defined from the regulatory system in agreement with the applicant.
Finally, whether from abroad or in country, an increase in the number of applications
is expected. The trend displayed in Figure 2.5 for the overall evolution of the regulatory
system with regard to the number of applications submitted to the system, may be attributed
to a combination of the normal dynamic of submissions with the changes and adjustments
that the framework underwent since its origin. As to the third wave observed under the
current regulatory system, it may be caused by a normal dynamic of submissions. A welldesigned and implemented biosafety framework is necessary to guarantee quality,
consistency, clarity and transparency for the success of the decision-making process.
158

APPENDIX

159

APPENDIX

Table A2.1. Summary of applications from the period of 1995-2011 by crop, event, trait, gene, year of application and authorizing agency.
Event name between brackets corresponds to the OECD ID.

Crop
Corn
Corn

Event

Trait/Gene(s)
Unspecified in record
1
available
Unspecified in record
available
Insect resistance
(lepidopteran) and
herbicide tolerance
(glufosinate ammonium)/
Cry1Ab,bar
Herbicide tolerance
(glufosinate ammonium)/
pat
Insect resistance
(lepidopteran) and
herbicide tolerance
(glufosinate ammonium)/
Cry9C, bar

Unspecified in record
available
Unspecified in record
available

Corn

176
(SYN-EV176-9)

Corn

T25/Liberty LinkTM
(ACS-ZM003-2)

Corn

CBH351/StarlinkTM
ACS-ZM004-3

TM

Corn

GA21/Roundup Ready
(MON-00021-9)

Year of
application/
authorization

Use
b)

---

1995

DGSA (Uruguay, 1995a)

b)

---

1996

DGSA (Uruguay, 1996e)

c)

---

1998

DGSA (Uruguay, 1998)

b),d)

---

1998

DGSA (Uruguay, 1998)

b), c),
d)

---

1998

DGSA (Uruguay, 1998d)

b), c),
d)

---

1998

DGSA (Uruguay, 1998)

---

1998

DGSA (Uruguay, 1998e)

2009
2009

2009
2011

GNBio (Uruguay, 2009)
GNBio (Uruguay, 2011)

2

b), c),
d)
c)
e)

Herbicide tolerance
(glyphosate)/ mepsps

160

Authorizing agency

Table A2.1 (cont’d).
a)
b), c),
d)
Corn

MON810
(MON-00810-6)

Insect resistance
(lepidopteran)/ Cry1Ab

---

1998

DGSA (Uruguay, 1998b)

---

1998

DGSA (Uruguay, 1998c)

Corn

NK603/Roundup
Ready®
(MON-00603-6)

161

---

e)

---

2004

e)

2011
2003
---

2004
2005

c)

2005

---

b)
c)
e)

Herbicide tolerance
(glyphosate)/ CP4 epsps

---

b)
b)

Corn

2011

c)
Insect resistance
(lepidopteran) and
herbicide tolerance
(glufosinate ammonium)/
Cry1Ab, pat

2002

e)

BT11
(SYN-BT011-1)

e)

2003

2010
2009
2010

2010
2009
2011

MEF-MGAP (Uruguay,
2003a)
MVOTMA (Uruguay, 2003b)
Harmonization with
resolutions for new events in
corn - GNBio
(Uruguay, 2011f)
--MEF-MGAP (Uruguay,
2004b)
MVOTMA (Uruguay, 2004c)
Harmonization with
resolutions for new events in
corn - GNBio
(Uruguay, 2011g)
DGSA (Uruguay, 2004a)
DGSA (Uruguay,2005b)
Application rescinded, File
MGAP 2005/7/4/1/1055 of
06/10/05.
GNBio (Uruguay, 2010)
GNBio (Uruguay, 2009)
GNBio (Uruguay, 2011d)

Table A2.1 (cont’d).

Corn

Corn

Corn

Corn

MON810XNK603/
Roundup Ready®
YieldGard
(MON-00810-6X
MON-00603-6)

Insect resistance
(lepidopteran) X herbicide
tolerance
(glyphosate)/Cry1Ab X
cp4 epsps

GA21XBT11
(MON00021-9X
SYN-BT011-1)

Herbicide tolerance
(glyphosate) X Insect
resistance (lepidopteran)
and herbicide tolerance
(glufosinate ammonium)/
mepsps X Cry1Ab, pat/

TC1507
(DAS-01507-1)

TC1507XNK603
(DAS-01507-1 X
MON-00603-6)

Insect resistance
(lepidopteran) and
herbicide tolerance
(glufosinate ammonium)/
Cry1Fa2, pat
Insect resistance
(lepidopteran) and
herbicide tolerance
(glufosinate ammonium)
X Herbicide tolerance
(glyphosate) / Cry1Fa2,
pat X cp4 epsps
162

b)
b)

2003
---

2004
2005

c)

2005

---

b)
c)
e)
c)

2010
2010
2010
2009

2010
2010
2011
2009

DGSA (Uruguay, 2004d)
DGSA (Uruguay, 2005c)
Application rescinded, File
MGAP 2005/7/4/1/1056 of
06/10/05.
GNBio (Uruguay, 2010)
GNBio (Uruguay, 2010)
GNBio (Uruguay, 2011e)
GNBio (Uruguay, 2009)

e)

2009

2011

GNBio (Uruguay, 2011b)

c)

2005

---

e)

2005

---

c)
e)

2009
2009

2009
2011

Application rescinded, File
MGAP 2005/7/4/1/0575 of
04/04/05.
Application rescinded, File
MGAP 2005/7/4/1/0575 of
04/04/05.
GNBio (Uruguay, 2009)
GNBio (Uruguay, 2011a)

c)

2009

2009

GNBio (Uruguay, 2009)

Table A2.1 (cont’d).

Corn

Corn

Corn

Soybean

Soybean

Herbicide tolerance
(glyphosate) X Insect
resistance (lepidopteran)
X Insect resistance
(lepidopteran) and
herbicide tolerance
(glufosinate ammonium)/
mepsps X Vip3Aa20 X
Cry1Ab, pat

c)

2009

2009

GNBio (Uruguay, 2010)

e)

2009

---

Under analysis

Insect resistance
(lepidopteran) X Insect
MON89034XMON88017 resistance (coleopterans)
(MON89034-3X
and Herbicide tolerance
MON88017-3)
(glyphosate)/Cry1A.105,
Cry2Ab2 X Cry3Bb1, cp4
epsps
Insect resistance
MON89034XNK603
(lepidopteran) X
(MON89034-3X
Herbicide tolerance
MON-00603-6)
(glyphosate)/Cry1A.105,
Cry2Ab2 X cp4 epsps
GTS 40-3-2/
Herbicide tolerance
(Roundup Ready®)
(glyphosate)/ cp4 epsps
(MON-04032-6)
Herbicide tolerance
FG74 (CPU)
(isoxaflutole and
(none OECD ID)
glyphosate)/hppd, epsps

b)

2010

2010

GNBio (Uruguay, 2010)

c)

2010

2010

GNBio (Uruguay, 2010)

e)

2010

---

Under analysis

b)

2011

---

Under analysis

b)

2011

---

Under analysis

c)

---

1996

DGSA (Uruguay, 1996b)

e)

---

1996

DGSA (Uruguay, 1996d)

b)

2005

---

Application rescinded, File
MGAP 2005/7/4/1/2153 of
10/31/05

GA21XMIR162XBT11
(MON00021-9X
SYN-IR162-4X
SYN-BT011-1)

163

Table A2.1 (cont’d).
d)

2009

2009

GNBio (Uruguay, 2009c)

2010

2010

GNBio (Uruguay, 2010a)

2010

2010

GNBio (Uruguay, 2010b)

(d)

2010

2010

GNBio (Uruguay, 2010c)

2010

2010

GNBio (Uruguay, 2010)

c)

2010

2010

GNBio (Uruguay, 2010)

(d)

2011

---

Under analysis

(d)

2011

---

Under analysis

(d)

2011

---

Under analysis

b)

2010

2010

GNBio (Uruguay, 2010)

c)

2010

2010

GNBio (Uruguay, 2010)

d)

2010

2010

GNBio (Uruguay, 2010)

(d)

2010

2010

GNBio (Uruguay, 2010)

b)

2011

---

Under analysis

(d)

2011

---

Under analysis

e)

164

GNBio (Uruguay, 2009b)

b)

Soybean

2009

(d)

Herbicide tolerance
MON89788XMON87701
(glyphosate) X Insect
(MON-89788-1
resistance (lepidopteran)/
XMON87701-2)
cp4 epsps X Cry1Ac

2009

(d)
Herbicide tolerance
(glyphosate)/ cp4 epsps

GNBio (Uruguay, 2009a)

(d)

MON89788
(MON-89788-1)

2009

(d)

Soybean

2009

2011

---

Under analysis

Table A2.1 (cont’d).
d)

Soybean

A2704-12
(ACS-GM005-3)

A5547-127
(ACS-GM006-4)

CP4
Eucalyptus
(none OECD ID)

2009

GNBio (Uruguay, 2009)

(d)

2009

2009

GNBio (Uruguay, 2009)

(d)

2010

2010

GNBio (Uruguay, 2010)

e)

2010

---

Under analysis

(d)

Soybean

2009

2011

---

Under analysis

d)

2011

---

Under analysis

(d)

2011

---

Under analysis

e)

2011

---

Under analysis

herbicide tolerance
(glufosinate ammonium)/
cp4 epsps

b)

---

1996

---

1996

Herbicide tolerance
(glufosinate
ammonium)/pat

Herbicide tolerance
(glufosinate
ammonium)/pat

Eucalyptus

11/25
(none OECD ID)

Low lignin content/ ---

b)

Rice

LLRice06
(ACS-OS001-4)

Herbicide tolerance
(glufosinate ammonium)/
(bar)

b)

Rice

LLRice62
(ACS-OS002-5)

Herbicide tolerance
(glufosinate ammonium)/
(bar)

165

DGSA (Uruguay, 1996c)

DGSA (Uruguay, 1996f)
Authorized but trials not
done.

c)

2005

---

e)

2005

---

Application rescinded, File
MGAP 2005/7/4/1/0565 of
04/01/05
Application rescinded, File
MGAP 2005/7/4/1/0565 of
04/01/05

Table A2.1 (cont’d).

White
clover

ATMYB32-IPT
(none OECD ID)

Delayed flowering and
delayed foliar and
peduncle senescence by
increased cytokinins
biosynthesis/ (ipt)
(Capdevielle and García,
2005)

b)

---

2005

DGSA (Uruguay, 2005a)

b)

---

2007

DGSA (Uruguay, 2007)

Categories of uses:
Color code according to the framework period:
a) Contained experiment.
b) Field trial for: research, agronomic assessment, demonstration
1995-2000
for propaganda.
2000-2007
c) Field trial for National Register of Cultivars.
d) Counter season seed multiplication under biosafety controlled
conditions – authorization for the use of the event is issued one
time, the owner company applies; (d) authorization for seed
2008- present
production is issued each season, local companies apply.
e) Deregulation (commercial planting, food and feed)
1. The first two authorizations in 1995 and 1996 do not specified the event. Probably these two unspecified resolutions
corresponds to any of the first events submitted, 176, T25, or CBH351 (Bayce D, Manager of the Uruguayan Seed Chamber,
2011 Personal Communication).
2. In the cases where the resolution was issued for more than one use, it is indicated in bold the use performed.

166

Table A2.2. Specific information required in the Uruguayan application form for the areas of concerns of molecular characterization, food safety
and environmental security (Parts B, C and D of the form). The numbering corresponds to the form. Missing numbering correspond to
information requested for the evaluation of other aspects different from the areas of concerns.

MOLECULAR CHARACTERIZATION (PART B)
Specific information required by area of concern
Description of the genetic elements inserted in the GE plant
B2 Molecular biology of the donor-vector-recipient system. A detailed description including:
…
B2.4 Final construction map (cassette) with the restriction sites that allow to reproduce the determination of the number of copies
inserted.
B2.5 Description of all the elements included in the cassette/s used for the transformation, including for each element: its position
in the vector and in the insert, size (pb), donor organism, whether it was modified, function (in the donor and receiving
organisms), probe and/or its sequence.
B3 Detailed description of the genetic elements inserted in the receiving organisms (GE plant), indicating:
B3.1 Subcelular location of the event
B3.2 Molecular analysis of the insertion (event characterization) including:
B3.2.1 number of integration sites
B3.2.2 number of copies of each gene
B3.2.3 whether occurred insertion of portions of genes.
B3.3 Genome sequences flanking the insert (event)
B3.4 Description of all the elements inserted in the GE plant genome, including for each element: size (pb), function, whether it is
a sequence transcribed but not translated in the GE plant, molecular mechanism of its expression, whether the element confers a
non required function for the expected phenotype.
B3.5 To indicate the regions of the vector that have been incorporated in GE plant.
B3.6 Presence/absence of fragments of the insert in regions of the GE plant genome outside the region of the functional insertion
B3.7 Capacity of the construction to transfer genes by transposition, recombination, conjugation, integration or other mechanism
that could occur in the GE plant or in relation to other organisms.
B3.8 Information regarding the possibility of transpositions and/or rearrangements inside the insert once in the GE plant (respect
167

Table A2.2.(cont´d).
to the position the elements had in the vector), and/or of/with portions of the GE plant genome and in the flanking regions.
B3.9 Probability that the transcription process continues outside the insert to the GE plant genome ignoring termination signals, as
well as the probability of transcription and translation of fusion proteins or the generation of new open reading frames as
consequence of the insertion.
Description of the products from the genetic elements expressed in the GE plant.
B4 Detailed description of the products from the genetic elements expressed in the GE plant
B4.1 Description including for each genetic element: kind of the expression product (protein, RNA), molecular characterization of
the product, amino acid sequence, biological activity of the product in the GE plant indicating specific function and molecular
mechanism for its function, tissue/organ where is present, level of expression and its temporal evolution regarding the GE plant
cycle.
B4.2 Submit structural and functional analysis if there were performed using high-throughput methods of genomic,
transcriptomic, proteomic or metabolomic.
B4.3 Analysis to determine homology of the expressed products sequences with known sequences of expression products of
pathogens, toxins or allergens.
B5 Specific information for stacked events
B5.1 To inform whether different phenotypic characteristics than the ones expected occur from the expression of the individual
events.
B5.2 To inform whether occur interactions (or there are reasons to expect them to occur) among the genes from the individual
events, and its consequences.
Genetic stability
B8 Genetic stability
B8.1 Segregation and transfer to the progeny
B8.2 Molecular analysis to confirm the genetic stability (Southern blots, PCR).

168

Table A2.2. (cont’d).
FOOD SAFETY (PART C)
History of use and familiarity
C1 History of use and familiarity
C1.1 History of use of the conventional counterpart
C1.2 History of use of the protein expressed by the donor organism
C1.3 Aptitude of the GE plant or its derivatives to be used as food, in case that the use of the GE plant as food were new
Substantial equivalence
C2 Food and feed safety analysis
C2.1 To indicate if the nutritional quality of the food could be altered by the event
C2.2 To indicate if the GE plant is capable of produce metabolites that can cause adverse effects in the consumer (human or
animal)
C2.3 Quali-quantitative chemical composition of the GE plant and its derivatives if corresponds and its comparison with
conventional counterpart regarding: macro and micronutrients and anti-nutrients.
Digestibility of the GE protein
C2.4 Absorption, distribution and biotransformation of food components (nutrients and non nutrients) “in vitro” or “in vivo”
C2.5 Nutrients bioavailability in case of a the GE plant non substantially equivalent
Pathogenicity in mammals
C2.6 Pathogenicity in mammals

169

Table A2.2. (cont’d).
Allergenicity
C2.7 Allergenicity
C2.7.1 Bioinformatic analysis of the expressed proteins
C2.7.2 Identification of allergens in donor and receiving species.
C2.7.3 Bioinformatic analysis looking for homology of the expression products with known allergens
C2.7.4 To provide other features used as indicators of allergens such as: molecular weight, food levels, protein resistance to
food processing (heat or other), in vitro digestibility.
Toxicity
C2.8 Toxicity
C2.8.1 Toxins and antinutrient factors naturally present in donor and receiving organism.
C2.8.2 Bioinformatic analysis looking for homology of the expression products with known toxins
C2.8.3 Acute toxicological tests of pure proteins with no history of use
C2.8.4 Subchronic or chronic tests of pure protein, where appropriate
C2.8.5 Subchronic or chronic tests of food, where appropriate.
Carcinogenic and teratology studies
C2.9 Carcinogenic and teratology studies in the short and medium term, where appropriate.
Other considerations
C3 Other considerations
C3.1 Functional characterization of the GE plant and food derived from it, compared with its homolog.
C3.2 Whether there are changes in the way of the food use, processing or cooking, compared with its homolog.
C3.3 When using gene markers that confer antibiotic resistance, see considerations of Codex Alimentarius (CAC GL 45-2003,
pág 8-9, paragraph 55-58.

170

Table A2.2. (cont’d).
ENVIRONMENTAL SECURITY (PART D)
Characterization of the receiving organism (homolog) used as comparator.
D1 Information of the GE plant
D1.1 Characterization of the receiving organism/parental organism/homolog
D1.1.1 Centre of origin and genetic diversification
D1.1.2 Geographic distribution
D1.1.3 Description of the natural habitat
D1.1.4 Biological function of the specie in the ecosystem
D1.1.5 Pathogenicity, toxicity and allergenicity of the species
D1.1.6 Phenotypic characteristics of the species
D1.1.7 Phenological phases and growth rate or duration of each phase
D1.1.8 Flower and reproductive biology, factors that affect reproduction
D1.1.9 Pollen viability and longevity
D1.1.10 Pollen dispersal mechanisms
D1.1.11 Potential pollinator agents and its distribution in Uruguay
D1.1.12 Kind of fruit dehiscence
D1.1.13 Natural seed dispersal mechanisms
D1.1.14 Dormancy and seed capability of surviving after a long period of dormancy
D1.1.15 Description of periods of life latent conditions or inactivity of the plant.
D1.1.16 Survival structures and their capacity of persistence in the growing area and natural ecosystem. Factor that affect this
capacity.
D1.1.17 Ability and mechanism of competence and dispersion in the growing area and natural ecosystem. Factors that affect
this capacity.
D1.1.18 Whether the species has features that classify it as an invasive species or as potential invasive species.
D1.1.19 Whether the species has features that classify it as a weed or potential weed.

171

Table A2.2. (cont’d).
Characterization of the GE plant.
D1.2 Characterization of the GE plant
D1.2.1 To determine if there are any change in the biology of the plant as a consequence of the genetic modification compared
with its homolog, for the aspects described in item D1.1 (D1.1.1 to D1.1.19)
D1.2.2 Effects on the GE plant of the genetic elements introduced and their expression.
D1.2.2.1 Physiologic and/or metabolic effects on the GE plant
D1.2.2.2 Pleiotropic effects that could lead in the expression of allergic or toxic proteins or an increase or the production of
new secondary metabolites.
D1.2.2.3 In the case of stacked events, to inform whether different phenotypic characteristics than the ones expected occur
from the expression of the individual events.
D1.2.2.4 To indicate other risk factors derived from the presence of the introduced genetic elements or its expression
products.
D1.2.3 Phenotypic stability of the GE plant
D1.2.3.1 Inheritance pattern of the introduced trait.
D1.2.3.2 Phenotypic stability indicating the number of generations in which it was verified.
D1.2.3.3 Frequency of reversion or loss of the genetic material.
D1.3 Detection methods. Extend the information submitted in item B7.1 by including whether there are phenotypic markers or
others that allow the GE plant identification in the field.

172

Table A2.2. (cont’d).
Characterization of the receiving environment
D2 Information of the receiving environment
D2.1 Ecological characteristics of the area where the GE plant would be released, including for example wind direction, existence
of a water table, proximity to watercourses and protection areas.
D2.2 Biological function of the GE plant in the receiving environment.
D2.3 How the GE plant responds to the biotic and abiotic environment of the area where the GE plant would be released.
D2.4 To indicate the GE plant taxonomic related species including related and closed-related cultivated and wild species
indicating if they are weeds or invasive species.
D2.5 Geographical distribution of taxonomic related species if indicated in D2.4
D2.6 Crossing mechanisms and frequency, if related species were indicated in item D2.4. Rate and stability of selfing and/or cross
pollination
D2.7 Probability of hybridization and introgression if compatible species were indicated in D2.4 and whether the hybrid will have
any selective advantage or to compete that would determine changes or losses in populations of the species.
D2.8 Possible interactions of the GE plant with other non vegetables organisms of the ecosystem that could lead in a change of the
number in natural predators, parasites, competitors, symbionts and hosts
D2.9 Impact on non-target organisms in the case of the GE plant with insect resistance traits
D2.10 Whether the GE plant is able to add or remove soil substances (nutrients or toxic substances) compared with its homolog,
and its effect on the soil microbial population.
D2.11 Impact on the receiving environment as a consequence of a change in the agronomic practices according to the
technological package associated to the trait introduced.
D2.12 Management measures to avoid possible unwanted effects (for example resistance development in insects originally
susceptible to Bt proteins)
D2.13 Management measures for monitoring possible adverse effects on the receiving environment in the long term.
D2.14 Coexistence feasibility. To indicate management measures to avoid adventitious presence of other production systems
present in the receiving environment.

173

Table A2.3. Summary of the number of applications in the period 1995-2011 by uses, crop, trait, gene, event, total applications and permits
issued.
1995-2000
Resolution
DGSA-CAAR

Framework
by period

Uses

Crops

Traits

4

a) (1)
b) (5)
c) (6)
e) (1)

3

Corn (9)
Soybean (2)
Eucalyptus (2)

4

ns (2)
IR (2)
HT (5)
IR/HT (3)
Low lignin (1)

(1)

2000-2007
Decree No. 249/000
CERV
1

3

2

4

3

4

2008-present
Decree No. 353/008
GNBIO/CGR/ERB/CAI

TOTAL
1995-2011

b) (7)
c) (6)
e) (4)

4

b) (8)
c) (10)
d) (18)
e) (10)

Corn (11)
Soybean (1)
Rice (3)
White clove (2)

2

Corn (20)
Soybean (26)

5

2

HT (24)
IR/HT (2) or
IR X HT (11) or
IR/HT X HT (3) or
IR/HT X IR (4) or
IR/HT X HT X IR (2)

5

IR (1)
HT (7)
IR/HT (4) or
IRXHT (3)
Delayed
senescence (2)

174

5

a)
b)
c)
d)
e)
Corn
Soybean
Eucalyptus
Rice
White clove
 IR
 HT
 IR/HT, IRXHT,
IR/HTXHT,
IR/HTXIR,
IR/HTXHTXIR
 Low ligning
content
 Delayed
senescence

Table A2.3. (cont’d).
1995-2000
Resolution
DGSA-CAAR

Framework
by period

Genes

Events

6

ns (2)
cry1Ab (4)
cry9c (1)
bar (3)
pat (1)
epsps (4)
low lig (1)

8

Corn (5)
Soybean (1)
Eucalyptus (2)

2000-2007
Decree No. 249/000
CERV

4

6

5

9

Applications

13

17

Permits
issued

13

10

2008-present
Decree No. 353/008
GNBIO/CGR/ERB/CAI

cry1Ab (6)
cry1Fa2(1)
pat (4)
bar (3)
epsps (7)
ipt (2)

9

cry1Ab (7)
cry1Fa2 (3)
cry2Ab2 (5)
cry1A105 (5)
cry3Bb1 (4)
cry1Ac (6)
Vip3Ab20 (2)
epsps (34)
pat (13)

Corn (5)
Soybean (1)
Rice (2)
White clove (1)

13

Corn (9)
Soybean (4)

Rescinded by use:
(b): Soybean (1)
(c): Corn (3), rice (1)
(e): Corn (1), rice (1)

175

46
6

31

Under analysis by use:
(b): Corn (2), Soybean (1)
(d): Soybean (7)
(e): Corn (2), Soybean (3)

TOTAL
1995-2011

13

27

cry1Ab
cry9c
cry1Fa2
cry2Ab2
cry1A105
cry3Bb1
cry1Ac
Vip3Ab20
epsps
pat
bar
low lig
ipt
Corn (16)
Soybean (6)
Eucalyptus (2)
Rice (2)
White clove (1)
68
55

Table A2.3. (cont’d).
2008-present
TOTAL
Decree No. 353/008
1995-2011
GNBIO/CGR/ERB/CAI
Corn:
GA21
Corn:
RR
GA21XBT11
Corn (7)
2 MON810
5
Deregulations 1
8
(soybean)
TC1507
Soybean (1)
BT11
NK603
NK603XMON810
1. Seven of the original applications where rescinded leaving a total of 10 applications analyzed, distributed by use as follows:
b) (6), c) (2), e) (2).
2. Seven of the original applications where rescinded leaving a total of 3 crops: corn (7), rice (1), white clove (2).
3. Seven of the original applications where rescinded leaving the following distribution by trait:
IR (1), HT (3), IR/HT (2) or IR X HT (2), Delayed senescence (2).
4. Seven of the original applications where rescinded leaving a total of 5 genes analyzed:
cry1Ab (5), pat (2), bar (1), epsps (4), ipt (2).
5. Seven of the original applications where rescinded leaving a total of 6 events analyzed: corn (4), rice (1), white clove (1).
6. The actual number corresponds to 32 resolutions issued by GNBio. The difference results from resolutions 32A and 32B that
harmonize old events in corn (GNBio No. 32A for MON810 and GNBio No. 32B for BT11).
ns – non-specified in the record available at the Biosafety Office – MGAP- Uruguay.
IR – Insect resistance
HT – Herbicide resistance
IR/HT – individual event with IR and HT
IRXHT – stacked plant with two events incorporated by conventional crossing
Categories of uses: a) Contained experiment
b) Field trial for research
c) Field trial for National Register of Cultivars
d)Seed multiplication
e) Deregulation (commercial planting, food and feed)
(1) The period 2007-2008 is not included since Decree No. 037/007 suspended the treatment of any new applications.
Framework
by period

1995-2000
Resolution
DGSA-CAAR

2000-2007
Decree No. 249/000
CERV

176

REFERENCES

177

REFERENCES

Bellon MR, Adato M, Becerril J, Mindek D (2003). The impact of improved maize
germplasm on poverty alleviation: the case of Tuxpen ˜o-derived material in Mexico:
Food Consumption and Nutrition Division discussion paper 162. International Food
Policy Research Institute. http://www.ifpri.org/divs/fcnd/dp/papers/fcndp162.pdf
Bellon MR, Berthaud J (2004) Transgenic Maize and the evolution of landrace diversity in
Mexico. The importance of farmers behaviour. Plant Physiol 134:883-888.
Bellon MR, Brush SB (1994) Keepers of maize in Chiapas. Mexico. Econ Bot 48: 196–209
Brookes G. 2008. Economic impacts of low level presence of not yet approved GMOs on the
EU food sector. Briefing document. GBC Ltd, UK. 48p.
Burkarta. 1969. Flora Ilustrada de Entre Ríos (Argentina). Tomo VI, II. INTA. Argentina
CODEX ALIMENTARIUS. 2001. Codex Alimentarius Commission – Procedural Manual –
Twelfth Edition. http://www.fao.org/DOCREP/005/Y2200E/y2200e00.htm#Contents
__________. 2003. Guideline for the conduct of food safety assessment of foods derived
from recombinant-DNA plants. Codex Alimentarius Commission, Joint FAO/WHO
Food Standards Programme, Rome. CAC/GL 45.
http://www.fao.org/docrep/011/a1554e/a1554e00.htm
__________. 2007. Working principles for risk analysis for food safety for application by
governments. CAC/GL 62-2007. 4p.
__________. 2009. Foods derived from modern biotechnology. Codex Alimentarius
Commission, Joint FAO/WHO Food Standards Programme, Rome.
CONVENTION ON BIOLOGICAL DIVERSITY (CBD). 1992. United Nations
Environment Programme. 30p. http://www.cbd.int/
Craig W, Tepfer M, Degrassi G and Ripandelli D. 2008. An overview of general
features of risk assessments of genetically modified crops. Euphytica. 164:853 880.
CUS. 2003. Refuge instructions for planting genetically engineered corn. CUS, 2003.
Demeke T, Perry DJ and Scowcroft WR. 2005. Adventitious presence of GMOs: Scientific
overview for Canadian grains. Can.J.Plant Sci. 86:1-23.
EUROPEAN FOOD SAFETY AUTHORITY (EFSA). 2007. Guidance Document of the
Scientific Panel on Genetically Modified Organisms for the risk assessment of
genetically modified plants containing stacked transformation events. EFSA
Journal 512: 1-5

178

__________. 2010a. Panel on Genetically Modified Organisms (OGM). 2010.
Guidance on the environmental risk assessment of genetically modified plants.
EFSA Journal 8(11):1879 111pp.
__________. 2010b. EFSA Panel on Genetically Modified Organisms (GMO). Scientific
Opinion on the assessment of allergenicity of GM plants and microorganisms and
derived food and feed. EFSA Journal, 8(7):1700, 168pp.
__________. 2011a. Panel on Genetically Modified Organisms (OGM).
2011a.Guidance on selection of comparators for the risk assessment of genetically
modified plants and derived food and feed. EFSA Journal 9(5):2149 21pp.
__________. 2011b. Panel on Genetically Modified Organisms (OGM). Guidance for
risk assessment of food and feed from genetically modified plants. EFSA
Journal 9(5):2150.
Ellstrand NC and Hoffman CA. 1990. Hybridization as an Avenue of Escape for Engineered
Genes. Strategies for risk reduction. BioScience 6(40):438-442.
Ellstrand NC. 2003. Current knowledge of gene flow in plants: implications for transgene
flow. Phil. Trans. R. Soc. Lond. B 358:1163–1170.
European Coexistence Bureau (ECoB), 2010
EUROPEAN COMMISSION (EC), Rapid Alert System for Food and Feed (RASFF). 2006.
Annual Report. pp. 37-38.
__________. 2007. Annual Report. pp.24-44.
EUROPEAN COMMISSION (EC). 2001. Regulation No. 1829/2003.
__________. 2002a. Commission Decision (2002/623/EC) of 24 July 2002 establishing
guidance notes supplementing Annex II to Directive 2001/18/EC of the European
Parliament and of the Council on the deliberate release into the environment of
genetically modified organisms and repealing Council
__________. 2002b. Regulation (EC) No 178/2002 of the European Parliament and of the
Council of 28 January 2002 laying down the general principles and requirements of
food law, establishing the European Food Safety Authority and laying down procedures
in matters of food safety. Official Journal of the European Communities L 31:1-24.
__________. 2003. Directive 2003/18/EC of the European Parliament and of the Council, on
the deliberate release into the environment of genetically modified organisms, 12
March 2001.

__________. 2009. Report from the Commission to the Council and the European Parliament
on the coexistence of genetically modified crops with conventional and organic
farming. Implementation of national measures. Comisión of the European
Communities. Brussels.
179

Falck-Zepeda J and Zambrano P. 2011. Bio-innovations and the economics of biosafety
regulatory decisión making and design in developing countries. In: Grumet G, Hancock
J, Maredia K and Weebaddee C. ed. Environmental Safety of Genetically Engineered
Crops. East Lansing, USA, Michigan State University pp 157-172.
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS (FAO).
1996. Biotechnology and food safety, Report of a joint FAO/WHO consultation. FAO
Food and Nutrition Paper 61, Food and Agriculture Organisation of the United Nations,
Rome
__________. 2000. Safety aspects of genetically modified foods of plant origin
Report of a Joint FAO/WHO Expert Consultation on Foods Derived from
Biotechnology. Document WHO/SDE/PHE/FOS/00.6, WHO, Geneva, 2000.
http://www.fao.org/wairdocs/ae584e/ae584e00.htm
__________. 2001. FAO Glossary of Biotechnology for Food and Agriculture.
__________. 2007. Instrumentos de la FAO sobre la bioseguridad (Biosecurity toolkit).
Roma, Italia. 148p.
__________. 2009a. Food safety assessment of genetically engineered food. Tools for
trainers. Food and Agriculture Organization of the United Nation, Rome, 201pp.
__________. 2009b. Regional Workshop on criteria for the management of biosafety.
Curitiba, Brazil, 23-24 March, 2009. In: FAO Regional Project TCP/RLA/3109 (D):
Development of technical reference tools for the management of biosafety in expanded
MERCOSUR countries.
García T. 2011. Biosecurity in Latin America. Lecture by Tea García in the videoconference
“Biotechnology crops in the world, IICA May 18th 2011.
García-Alonso M., Jacobs E., Raybould A., Nickson T., Sowig P., Willekens H., Van der
Kouwe P., Layton R., Amijee F., Fuentes A. and Tencalla F. 2006. A tired system for
assessing the risk of genetically modified plants to non-target organisms. Environ.
Biosafety Res. 5:57-65
GIM report, 2007. Review of the Uruguayan regulatory system and possible scenarios
analyzed by the interministries working group (GIM) created by Decree No. 037/007.
Hancock JF. 2003. A framework for assessing the risk of transgenic crops. Bioscience
53:512-519.
Hill RA and Sendashonga C. 2003. Review. General principles for risk assessment of living
modified organisms: Lessons from chemical risk assessment. Environ. Biosafety Res.
2:81-88.
Hill, R. 2005. Conceptualizing risk assessment methodology for genetically
modified organisms. Environmental Biosafety Research 4:67 -70.

180

Jhonson, K.; Raybould, A.; Hudson, M. and Poppy, G. 2006. How does scientific
risk assessment of GM crops fit within the wider risk analysis? Trends in Plant
Science 12(1):1-5.
LaReesa, Department of Biology, University of Nebraska, Omaha NE
Louette D, Charrier A, Berthaud J (1997) Insitu conservation of maize in Mexico: genetic
diversity and maize seed management in a traditional community. Econ Bot 51: 20–38.
McCammon S. 2010. Low-Level Presence (LLP): United States. In: Workshop on AP/LLP,
May 4-5, Buenos Aires, Argentina, Seed Association of the Americas (SAA). 25p.
Nap JP, Metz PLJ, Escaler M and Conner AJ. 2003. The release of genetically modified crops
into the environment Part I. Overview of current status and regulations. The Plant
Journal 33:1–18.
Organization for Economic Co-operation and Development (OECD). 1993. Safety
considerations for biotechnology: scale-up of crop plants. 43p.
__________.1995. Harmonization of biotechnology regulation: Analysis of information
elements used in the assessment of certain products of modern biotechnology. OECD
Environment Monograph No. 100, Paris, France.
Ortíz GS. 2011. Comentarios sobre las recientes aprobacones de maíz GM en México. Power
Point presentation. In: Cultivos biotecnológicos en México. In: Videoconference
“Estado mundial de la comercialización de cultivos biotecnológicos en 2010 según el
informe #42 del ISAAA.”, May 17-18, 2011, IICA. www.iica.org.uy - www.iica.int
Perales H, Brush SB, Qualset CO (2003) Landraces of maize in central Mexico: an altitudinal
transect. Econ Bot 57: 7–20.
Planning and Budget Office. OPP. 2009. Uruguayan strategy III Century. Productive aspects.
Planning and development strategy area, OPP. Montevideo, Uruguay. 136p.
Production Cabinet MGAP, MEF, MIEM, MRREE, MTSS, MTOP, MTD, OPP. 2010.
Tripartite Sectoral Council Bio and Nanotechnology. http://gp.gub.uy/en/node/188/4
__________. 2011. Biotechnology Sectoral Plan 2011-2020. Montevideo, Uruguay. 49p.
http://gp.gub.uy/es/node/333
Romeis J,Bartsch D, Bigler F, Candolfi MP, Gielkens MMC, Hartley SE, Hellmich
RL,Huesing JE, Jepson PC, Layton R,Quemada H,Raybould A, Rose RI, Schiemann J,
Sears MK, Shelton AM, Sweet J, Vaituzis Z, Wolt JD. 2008. Assessment of risk of
insect-resistant transgenic crops to nontarget arthropods. NatBiotechno l26:203–208
__________. Lawo NC and Raybould A. 2009. Making effective use of existing data for
case-by-case risk assessment of genetically engineered crops. Journal of Applied
Entomology. 133(8):571-583.

181

__________. Meissle M. 2010. Non-target risk assessment of Bt crops - Cry protein uptake
by aphids. J Appl Ent. 135(1-2):1-6.
__________. Hellmich R., Candolfi MP., Carstens K., De Schrijver A., Gatehouse MR,
Herman R., Huesing JE, McLean MA., Raybould A., Shelton AM., Waggoner A. 2011.
Recommendations for the design of laboratory studies on non-target arthropods for risk
assessment of genetically engineered plants. Transgenic Res 20:1-22.
Rose RI. 2007.White paper on tier-based testing for the effects of proteinaceous Insecticidal
plant-incorporated protectants on non-target invertebrates for regulatory risk
assessment (USDA-APHIS and US Environmental Protection Agency, Washington,
DC.
Rosergurtt B, Arrillaga B and Izaquirre P. 1970. Gramíneas uruguayas. Dpto. Publicaciones.
Universidad de la República. Uruguay
Secretariat of the Convention on Biological Diversity (2000). Cartagena Protocol on
Biosafety to the Convention on Biological Diversity: text and annexes. Montreal:
Secretariat of the Convention on Biological Diversity. 30p.
Snow AA and Morán Palma P. 1997. Commercialization of Transgenic Plants: Potential
Ecological Risks. Will evolutionary effects of engineered crops exacerbate weed and
pest problems? BioScience 47(2):86-96.
Souto G. 2010. Multiplicación de semilla en contraestación para exportación: características,
alcances e impactos. Counter seed production for exporting: characteristics, scope and
impacts. In: Annual Book of the Office of Planning and Agricultural Policy of the
Ministry of Livestock, Agriculture and Fisheries (MGAP-OPYPA) December, 2010.
Montevideo, Uruguay. pp.353-363.
__________and Ferenczi A. 2010. Genetically Modified Organisms: Progress in the
implementation of the new regulatory system. In: Annual Book of the Office of
Planning and Agricultural Policy of the Ministry of Livestock, Agriculture and
Fisheries (MGAP-OPYPA) December, 2010. Montevideo, Uruguay. pp.278-285.
Speroni G (2010) Report of environmental risk assessment of transgenic corn in Uruguay. In:
Report of the Ad Hoc Group on gene flow and coexistence (GAHFG) regarding
environmental risk assessment of GE corn events for deregulation, GAHFG,
07/09/2010.
Traynor PL, Frederick RJ, Koch M. 2002. A workbook for technical training. Biosafety and
risk assessment in agricultural biotechnology. The agricultural biotechnology support
project, Institute of International Agriculture, Michigan State University. Lansing, MI.
142p.
Uchtmann DL. 2002. StarLinkTM – A case study of agricultural biotechnology regulation.
Drake Journal of Agricultural Law. 7: 159-211.
UNEP. 1992. Convention on Biological Diversity. United Nations.

182

URUGUAY 2000a. Decree 249/000 of 08/30/00 for the creation of the Commission on Risk
Assessment of Genetically Engineered Plants (CERV), MGAP, MEF, MSP,
MVOTMA.
URUGUAY 2010.GAHFG Report Annex 1
URUGUAY. 2011. Law No. 18,792 of August 3rd, 2011 that approves the Cartagena
Protocol on Biosafety to the Convention on Biological Diversity.
http://www.parlamento.gub.uy/htmlstat/pl/protocolos/prot-ap-37959.htm.
URUGUAY 2011 CGR minute No 73 of 04/12/11
URUGUAY 2011 CGR reports No. 27-31 of 05/13/11. Recommendations to GNBio
regarding corn events applied for deregulation.
URUGUAY CERV 2005. Proposal of coexistence policy.
URUGUAY, 2000b. General Environmental Protection Act No. 17283 of 11/28/00.
URUGUAY, 2005. Diario el País. March 1st, 2005.
URUGUAY, 2007 Report of the institutional working group (GTI) elevated to the
interministries group (GIM) within the framework of the decree 037/007.
URUGUAY, 2007Report of the working group on labeling (GTE) elevated to the
interministries group (GIM) within the framework of the decree 037/007.
URUGUAY, 2011. ERB/CAI reports on environmental risk assessment of corn events that
applied for deregulation. ERB/CAI, 03/11/11.
URUGUAY, MEF-MGAP. 2003a. Deregulation of corn containing the event MON810.
MEF-MGAP resolution without number of 06/20/03.
URUGUAY, MEF-MGAP. 2004b. Deregulation of corn containing the event BT11. MEFMGAP resolution 290/004 of 05/05/04.
URUGUAY, MGAP. 1995a. Creation of a Risk Analysis Committee for transgenic corn.
DGSA Resolution of 07/08/95.
URUGUAY, MGAP. 1995b. Authorization for research field trial with transgenic corn.
DGSA Resolution of 11/06/95.
URUGUAY, MGAP. 1995c. Creation of a Risk Analysis Committee for transgenic corn.
DGSA resolution of 12/08/95.
URUGUAY, MGAP. 1996a. Creation of a Risk Analysis Committee for transgenic plants.
DGSA resolution of 01/13/96.
URUGUAY, MGAP. 1996b. Authorization for field trials with transgenic soybean with the
event 40-3-2. DGSA resolution of 01/23/96.
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URUGUAY, MGAP. 1996c. Authorization for research field trials with eucalyptus tolerant to
the herbicide glyphosate. DGSA resolution of 09/27/96.
URUGUAY, MGAP. 1996d. Deregulation of Soybean 40-3-2. DGSA Resolution 10/02/96.
URUGUAY, MGAP. 1996e. Authorization for field trial with transgenic corn. DGSA
Resolution of 10/28/96.
URUGUAY, MGAP. 1996f. Authorization for research field trials with transgenic eucalyptus
(low lignin content). DGSA resolution of 11/14/96.
URUGUAY, MGAP. 1998. Authorization for field trials for the national register of cultivars
with corn containing the event 176. DGSA resolution of 10/07/98.
URUGUAY, MGAP. 1998a. Authorization for field trials with corn containing the event 176.
DGSA resolution of 10/19/98.
URUGUAY, MGAP. 1998b. Authorization for research under contained conditions with corn
containing the event MON810. DGSA resolution of 10/19/98.
URUGUAY, MGAP. 1998c. Authorization for field trials for the national register of cultivars
with corn containing the event MON810. DGSA resolution of 10/19/98.
URUGUAY, MGAP. 1998d. Authorization for field trials for the national register of cultivars
with corn containing the event T25. DGSA resolution of 10/19/98.
URUGUAY, MGAP. 1998e. Authorization for field trials for the national register of cultivars
with corn containing the event GA21. DGSA resolution of 10/19/98.
URUGUAY, MGAP. 1998f. Authorization for research field trials with corn containing the
event CBH351. DGSA resolution of 10/19/98.
URUGUAY, MGAP. 2005a. Authorization for research field trials with white clove
containing the event ATMYB32-IPT. DGSA resolution of 03/11/05.
URUGUAY, MGAP. 2005b. Authorization for research field trials with corn containing the
event NK603. DGSA resolution of 06/30/05.
URUGUAY, MGAP. 2005c. Authorization for research field trials with corn containing the
event NK603XMON810. DGSA resolution of 06/30/05.
URUGUAY, MGAP. 2007. Authorization to conserve white clove containing the event
ATMYB32-IPT for future research. DGSA resolution of 08/15/07.
URUGUAY, MGAP. 2009. Authorization for field trials for the national register of cultivars
with corn containing the event GA21. GNBio resolution No. of 08/31/09.
URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011a. Deregulation of corn
containing the event TC1507. GNBio resolution No. 27 of 06/21/11.
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URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011b. Deregulation of corn
containing the event GA21XBT11. GNBio resolution No. 28 of 06/21/11.
URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011c. Deregulation of corn
containing the event GA21. GNBio resolution No. 29 of 06/21/11.
URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011d. Deregulation of corn
containing the event NK603. GNBio resolution No. 30 of 06/21/11.
URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011e. Deregulation of corn
containing the event NK603XMON810. GNBio resolution No. 31 of 06/21/11.
URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011f. Harmonization of
deregulation of corn containing the event MON810 with new regulation for transgenic
corn. GNBio resolution No. 32A of 06/21/11.
URUGUAY, MGAP-MEF-MVOTMA-MSP-MIEM-MRREE. 2011g. Harmonization of
deregulation of corn containing the event BT11 with new regulation for transgenic
corn. GNBio resolution No. 32B of 06/21/11.
URUGUAY, MGAP-MVOTMA-MSP-MEF. 2007b. Decree No. 037/007 of 01/29/07 that
suspends the analysis of any new application for authorization of transgenic plants for
any of the uses established in Decree No. 249/000.
URUGUAY, MGAP-MVOTMA-MSP-MEF. 2008. Decree No. 353/008 of 07/21/08 on
biosafety of genetically engineered plants and its parts. Amending Decrees: No. 535 of
11/03/08 and No.280 of 06/08/09.
URUGUAY, MGAP-OPYPA. 2010. Socio-economic report on soybean counter-season seed
production by Souto G., Office of Agricultural Planning and Policy – OPYPA.
URUGUAY, MVOTMA. 2003b. Conditions for the introduction, use, production and
commercialization of corn containing the event MON810. Consolidated text of
MVOTMA resolutions: 236A/003 of 07/28/03 and 276/003 of 09/01/03.
URUGUAY, MVOTMA. 2004c. Conditions for the introduction, use, production and
commercialization of corn containing the event BT11. MVOTMA resolution 292/004
of 06/09/04.
URUGUAY, MVOTMA. 2004d. Authorization for field trials with corn containing the event
NK603XMON810. DGSA resolution of 12/26/04.
URUGUAY, MVOTMA. 2007. National Biosafety Framework.BF
URUGUAY, MVOTMA-MGAP. 2006. Suspension of the use, production and
commercialization of seed of genetically engineered sweet corn of any event.
MVOTMA-MGAP resolution without number of 08/17/06.
URUGUAY. 2008b. Textos modificativos.
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URUGUAY. 2011. CGR minutes.
URUGUAY. MVOTMA. 2007a. Proposal for the development of a National Biosafety
Framework. DINAMA-PNUMA-FMAM. URU-04-009. 148p.
URUGUAY. National Biosafety Cabinet (GNBio). 2009. Uruguayan application form for
requesting authorization for the use of genetically engineered plants. GNBio, 2009.
40p. http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,1,619,O,S,0,,
URUGUAY. National Institute of Seeds (INASE). 1997. Law N° 16811 of February 1997 for
the creation of the National Institute of Seeds (INASE) as a non-state public entity.
URUGUAY. National Institute of Seeds (INASE). 2007. Resolution that authorizes the entry
in the national cultivar registration new cultivars after the first year of the two-year
requirement of agronomic field trials. Resolution No. 064/07 of 08/20/07.
http://www.inase.org.uy/normas/Resoluciones.aspx
URUGUAY. National Institute of Seeds (INASE). 2009. Law N° 18467 of February 2009
with modifications of Law N° 16811 of February 1997 of the creation of the
National Institute of Seeds (INASE).
URUGUAY. National Institute of Seeds. (INASE). National Register of Cultivars field trials
results, homepage. 2013. http://www.inase.org.uy/especiesCultivares/Default.aspx
URUGYA, MGAP. 2004a. Authorization for field trials with corn containing the event
NK603. DGSA resolution of 01/13/04.
US National Research Council (NRC). 1996. Understanding Risk – Informing Decisions in a
Democratic Society. Committee on Risk Assessment Methodology, National Research
Council. National Academy Press, Washington, D.C.
US, Environmental Protection Agency (EPA). 2001.FIFRA Scientific Advisory Panel. A set
of Scientific Issues Being Considered by the Environmental Protection Agency
Regarding: Assessment of Additional Scientific Information Concerning StarLinkTM
corn. SAP Report No. 2001-09. Arlington, VA:U.S. Environmental Protection Agency,
2001. http://www.epa.gov/oppbppd1/biopesticides/pips/tier-based-testing.pdf
Vidal, R. 2011. Report about landraces in Uruguay, an update.
Zerbino S. (from INIA) and Castiglioni E. (from UDELAR). Annual report during the period
2004/05 – 2009/10 of the monitoring plan and Management Pest Plan required in the
authorization for commercial release of the events in corn MON810 and BT11.
Zuloaga FO, Nicora EG, Rúgolo ZE, Morrone O, Pensiero J and Cialdella AM. 1994.
Catálogo de la familia Poaceae en la República Argentina.Monographs in Systematic
Botany. Missouri Botanical Garden. EUA

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CHAPTER III: COMPARISON OF THE URUGUAYAN REGULATORY SYSTEM
FOR GENETICALLY ENGINEERED CROPS WITH OTHER NATIONAL AND
REGIONAL SYSTEMS AND POTENTIAL FOR HARMONIZATION

INTRODUCTION
The resulting biosafety regulatory system that each country has in place reflects the
complex interaction between the political and economic situation, culture, environment and
scientific and regulatory capacity of each individual country. A comparative analysis of the
Uruguayan biosafety regulatory system with other frameworks is presented in this chapter.
The Uruguayan approach is compared with those of Argentina, Brazil and Paraguay, which
together form the Southern Common Market (MERCOSUR for its acronym in Spanish). The
objective is to identify from divergences new strategies for improvement of the Uruguayan
system, and also, to identify from commonalities potential approaches for harmonization
toward a regional system taking advantage of the already existing regional trade agreement
among the countries under analysis.
The information provided in this chapter is based on published documents and
scientific literature. In addition, I present information and opinions based on my experience
as the Technical Secretariat for the Interministries Working Group that elaborated the
currently effective Decree 353/008, and subsequently as the coordinator for the analysis of
the risk assessment working at the Risk Assessment on Biosafety agency (ERB). By working
to develop the regulatory system and subsequently at the regulatory agency I had the
opportunity to participate in various discussions and consultations among regulators from
different countries. The comparisons that follow include a description of possible plusses and
minuses of the risk analysis policies, with particular attention to guidelines and procedures

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that could be adopted regionally. The overview and comparison of approaches is focused on
field trials and commercialization of genetically engineered crops.

GENERAL DESCRIPTION OF BIOSAFETY FRAMEWORKS
Biosafety is a dynamic field and therefore the regulatory frameworks are in the
process of continuous revision and updating. This section provides a general description of
the history and current situation of the biosafety frameworks that have been implemented in
the Regional Trade Agreement MERCOSUR countries of Brazil, Argentina and Paraguay in
comparison with the regulatory system of Uruguay (see chapter 2 of this thesis).

Description of the Argentinean biosafety framework
Argentina was one of the first countries worldwide to establish a biosafety framework
with policies dating back to 1991 (Argentina, 1991, Nap et al. 2003). Argentina employs a
mixed regulatory system based on existing regulations in agriculture for plant protection
chemicals and new crop-specific regulations created to determine the conditions for GE-crop
development and release into the environment (Argentina, 1992, 2003a, 2003b, 2003c) and
for food safety assessment (Argentina, 2002). Regulations applied for the National Advisory
Commission on Agricultural Biotechnology (CONABIA for its acronym in Spanish) and the
National Health Service and Food Quality (SENASA) for risk assessment of GE organisms
are listed in Table 3.1 Additionally Argentina has in “parliament treatment” several proposed
bills related to different aspects of biotechnology including one specifically on genetically
modified organisms for agricultural, agroindustry and food industry production (Personal
Communication, Godoy P., General Director of the Biotechnology Directorate of SAGYP,
2011).

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Table 3.1. List of Argentinean specific regulations for GE organisms. (The date indicated in
Resolutions corresponds to the date that the decision comes into force, and corresponds to the
date of publication in the Official Gazette).

Norm
SAGyPA Resolution
No. 124/91 of
10/24/91
SAGyPA Resolution
No. 328/97 of
05/28/97
SAGyPA Resolution
No. 244/04 of
02/27/04
SAGyPA Resolution
No. 398/08 of
10/29/08 (modifies
No. 328/97 and
244/04)
SAGyPA Resolution
No. 656/92 of
07/30/92
SAGyPA Resolution
No. 39/03 of 07/17/03
(modifies No 656/92,
511/98 of 08/13/98
and derogates 289/97
of 05/14/97and
131/98 of 10/29/98)
SAGyPA Resolution
No. 644/03 of
12/18/03
(modifies Seed Law
No. 20247 of
04/16/73)
SAGyPA Resolution
No. 212/06 of
05/10/06
(modifies No. 644/03)
SAGyPA Resolution
No. 57/03 of 07/24/03
(modifies No 39/03
and
Biological/ecological
u organic production
Law No.25127 of
09/13/99)

Purpose

Advisory Body
to which it
applies

Creation of the National Advisory
Commission on Agricultural
Biotechnology (CONABIA)
Modifies composition of CONABIA
Modifies composition of CONABIA and
creates the Biotechnology Office

Modifies composition of CONABIA

Application form to analyze GE
microorganisms and GE plants

Modifies application form to analyze
environmental security of GE plants

Regulation of GM corn seed production
with events still regulated in Argentina

Modifies regulation of GM corn seed
production with events still regulated in
Argentina

Application form for experiments with GE
animals

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CONABIA

Table 3.1. (cont’d).
SAGyPA Resolution
No. 396/08 of
Modifies administrative process for
11/05/08 (modifies
application submission.
No. 212/06 and
39/03).
SAGyPA Resolution Regulation of GM soybean seed
No. 400/10 of
production with events still regulated in
08/24/10
Argentina
SENASA Resolution Creation of the Technical Advisory
No. 1265/99 of
Committee on the Use of Genetically
11/09/99
Modified Organisms (CTAUOGM)
SENASA Resolution
SENASA /
No. 412/02 of
CTAUOGM
05/17/02 (modifies
Application form to analyze food safety of
No. 289/97 of
GE products used as food/feed
05/14/97 and 511/98
of 08/13/98)
Source: Ministry of Economy and Production, Centre for Documentation and
Identification http://www.infoleg.gov.ar/

The National Advisory Commission on Agricultural Biotechnology (CONABIA)
conducts environmental risk assessment, and the Directorate of Food Safety and Quality
within SENASA conducts food/feed safety assessment. There is also the Directorate of
Agrifood Markets (DAM), which in the case of applications for commercial use, evaluates
the impact that the GE organisms could have on international trade of agriculture
commodities.
At the beginning, the Argentinean biosafety framework depended on the Secretariat of
Agriculture, Livestock, Fisheries and Food Supply (SAGyPA). SAGyPA was in the scope of
the Ministry of Economy and the authority to approve or not the use of GE organisms was the
Secretariat of SAGyPA. In 2009 the Ministry of Agriculture, Livestock and Fisheries
(MAGYP for its acronym in Spanish) was created (Argentina, 2009a, b) and SAGyPA
became one of its secretariats, named the Secretariat of Agriculture, Livestock and Fisheries
(SAGYP). The biosafety regulatory system continues to depend on SAGYP, but SAGYP is
now in the scope of the recently created Ministry of Agriculture. The authority to approve or
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not, the use of GE organisms is the Secretariat of SAGYP. Figure 3.1 provides a schematic
representation of the structure of the Argentinean regulatory system.
Since 1991 the National Advisory Commission on Agricultural Biotechnology
(CONABIA), was the commission with the responsibility to carry out the environmental risk
assessment and to design the biosafety conditions and risk management measures for the
environmental release of GE organisms (Argentina, 1991, 2011). CONABIA had
administrative support from the Technical Coordination of CONABIA, which later became
the Biosafety Office (Argentina, 2004). Due to the increase in the number of applications
requesting authorization for different uses of GE organisms, the Biosafety Office became the
Biotechnology Directorate (Argentina, 2008), which has responsibility together with
CONABIA for the follow-up and risk assessment of GE organisms.
The Biotechnology Directorate also participates in the development of the
biotechnology policy. The Directorate has five members, the director, a scientific consultant,
one responsible for the biosafety area, one responsible for the regulatory area and a technical
coordinator. Members of the Biotechnology Directorate are also members of CONABIA. The
General Director of the Biotechnology Directorate acts as the General Coordinator of
CONABIA.
CONABIA is a multidisciplinary and inter-institutional advisory commission that
provides technical support to the Secretariat of Agriculture. CONABIA is composed of
representatives from the public and private sector of agriculture biotechnology. The
composition of CONABIA, which was established originally in 1991 (Argentina, 1991), was
modified several times (Argentina, 1993, 1997, 2004). It is currently composed of 25
members from 17 institutions according to SAGyPA’s Resolution No. 398/008 (Argentina,
2008). A list of the institutions represented at CONABIA can be found in Table 3.3 at the end
of this section. For each institution there is one regular representative and one alternate. In

191

those institutions with more than one area of knowledge, there is one representative from
each area. The final recommendation to be forwarded to the Secretariat of Agriculture is
decided by majority vote. In case of tie, the General Coordinator of CONABIA has a double
vote.

Figure 3.1. Scheme of the Argentinean Biosafety Framework design. The specific advisory
bodies that compose the regulatory system and exclusively develop related tasks are indicated
in dark shading. Divisions that collaborate with the regulatory system for particular tasks are
indicated in light shading.

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In the National Health Service and Food Quality Office (SENASA) works the
Technical Advisory Committee on the Use of Genetically Modified Organisms (CTAUOGM
for its acronym in Spanish). CTAUOGM was created in 1999 by Resolution of SENASA as
indicated in Table 3.1 (Argentina, 1999). CTAUOGM is composed of representatives from
the public and private sector from the area of health and agriculture. Table 3.3 lists the
institutions represented at CTAUOGM. The National Directorate of Agrifood Safety and
Quality of SENASA presides over CTAUOGM but the coordination is performed by the
Agrifood Quality Directorate of SENASA.
The National Directorate of Agrifood Markets (DNM for its acronym in Spanish),
which became the Directorate of Agrifood Markets (DMA) after the creation of the Ministry
of Agriculture, assesses the economic appropriateness of commercialization of the GE
product under consideration. DMA does not perform a socioeconomic analysis. Workers at
DMA elaborate a business report with the analysis of markets and trade regarding the
convenience of authorizing the event under consideration.
Independent non-binding recommendation reports from the Directorate of Agrifood
Markets (DMA), the Biotechnology Directorate/CONABIA, and the National Health Service
and Food Quality (SENASA) are forwarded to the Secretariat of SAGYP for his
consideration and final decision.
Laboratory research activities with GE organisms are regulated by the Ministry of
Science, Technology and Innovation (MINCYT for its acronym in Spanish.) In 2001 was
created the Committee on Ethics in Science and Technology (CECTE for its acronym in
Spanish) by MINCYT Resolution No. 004/2001 (Table 3.1).
Comparison between the Argentinean and Uruguayan regulatory systems
The operational design of the Argentinean regulatory system highlights the
importance of the views of the trade office (DMA) in the decision-making and the lack of
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public participation and socioeconomic considerations. Although the system is based on risk
analysis methodology, its components: risk assessment, risk management and risk
communication, are not well distinguished. The risk assessment phase is performed
independently by the Biotechnology Directorate, based on CONABIA’s analysis regarding
environmental security, and SENASA’s assessment of food/feed safety. The Biotechnology
Directorate together with CONABIA, forwards a report to the Secretariat of SAGYP and
likewise SENASA. Although CONABIA interchanges information during the analysis
process with SENASA, the reports forwarded to the Secretariat of SAGYP are independent of
each other.
Regarding the risk management phase, the Biotechnology Directorate performs the
risk management, as it is responsible for the follow-up of released GE organisms and the
control of compliance of imposed biosafety measures. In addition, the Directorate of
Agrifood Markets (DMA) elaborates an independent report to the Secretariat of SAGYP with
regard to issues usually considered in the risk management phase (markets and trade). The
fact that the final decision is taken by the Secretariat of SAGYP based on non-binding
recommendations from the Biotechnology Directorate/CONABIA, SENASA and DMA,
suggests a separation between strictly biosafety issues and political, legal and economic
issues.
A positive practice of the Argentinean regulatory system is the proceeding established
in Regulation 39/2003 for the release into the environment of GE crops that considers a first
phase of evaluation for field trials and a second phase for commercial use. The field trials
performed under the so called “first phase” of the regulation Nº 39/2003 are mainly trials to
test the efficacy of the events for the developer to decide which cultivar to move forward to
commercialization, and so will require application for the “second phase”. This procedure
could be implemented in the Uruguayan framework as a way not only to include local

194

efficacy tests, but also for the assessment of any particular biosafety risk hypothesis that
needs to be tested locally. The first and second phase approach is also discussed in the last
section of this chapter as a procedure to be implemented regionally.
Comparing the structure and operation of the Uruguayan biosafety framework
(chapter 2 of this thesis) with the Argentinean system, it seems that the Uruguayan Risk
Assessment on Biosafety (ERB) committee performs similar tasks as the Argentinian
Biotechnology Directorate with regard to coordination of the risk assessment phase and
follow-up of released GE organisms. At the same time, the Institutional Coordination
Committee (CAI) and Ad Hoc Groups from Uruguay, perform similar tasks as CONABIA
does in Argentina. However, the Argentinean Biotechnology Directorate and CONABIA are
responsible for environmental issues while the Uruguayan ERB committee, the Institutional
Coordination Committee (CAI) and Ad Hoc Groups are also responsible for food and feed
safety. In Argentina food/feed safety is performed independently by CTAUOGM at
SENASA. The applicant submits the appropriate form at each office separately.
On the other hand, the Argentinian Biotechnology Directorate has a larger component
of risk management than ERB. ERB participates in risk management by recommending
biosafety measures, but the final recommendation to the Ministers is forwarded from the
Uruguayan Risk Management Commission (CGR), which performs exclusively risk
management tasks. In this sense, the Argentinian Biotechnology Directorate has similar
responsibilities as CGR, while CGR commission performs part of the Biotechnology
Directorate and the Directorate of Agrifood Markets (DMA)’s tasks. The Uruguayan CGR
commission analyzes economic issues regarding markets and trades as the Argentinean DMA
does, and performs the follow-up of released GE organisms regarding environmental security
as does the Argentinean Biotechnology Directorate. The CGR commission also includes the

195

analysis of socio-economic considerations and carries out the risk communication phase, both
of these aspects are not included in the Argentinean biosafety framework.
In summary, comparing the operation of both systems, the Uruguayan framework has
the environmental risk assessment process integrated with the food/feed safety analysis and
the risk management phase integrated at CGR. In the Argentinean system the signature of the
Secretariat of SAGYP is required for approval while in Uruguay the signature of six
Ministers is required.

Description of the Brazilian biosafety framework
Brazil has developed new norms specific for the regulation of genetically engineered
organisms. The regulation is based on the Biosafety Law No. 11.105 of 03/24/05, which is
implemented through the ordinances of Decree No. 5.591 of 11/22/05. Additionally there are
several provisions issued by the National Biosafety Council (CNBS) and the National
Biosafety Technical Commission (CTNBio) that regulate commercial release as well as
research and development of genetically modified organisms. Specific regulations on GE
organisms are listed in Table 3.2 The participating advisory bodies and commissions are
shown in Figure 3.2.
The National Biosafety Council (CNBS for its acronym in Spanish) is linked to the
Presidency of the Republic. CNBS is composed of 11 Ministers of State: the Minister of State
Chief of the Civil House Office of the Presidency of the Republic (chairperson of CNBS), the
Ministers of State of Science and Technology, Agrarian Development, Agriculture and
Supply, Justice, Health, Environment, Development, Industry and Foreign Trade, Foreign
Affairs, Defense and Special Secretary for Aquaculture and Fisheries of the Presidency of the
Republic (Brazil, 2005).

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Figure 3.2. Scheme of the Brazilian Biosafety Framework design. The specific advisory
bodies that compose the regulatory system and exclusively develop related tasks are indicated
in shading.

CNBS defines the responsibilities of the entities involved in the regulatory system as
the highest authority for formulating and implementing the national policy on biosafety. With
regard to the risk analysis process itself, CNBS performs the analysis of socio-economic
aspects and others of national interest if requested by the National Biosafety Technical
Commission (CTNBio for its acronym in Spanish). CNBS also decides on appeals for
commercial use of GE organisms and derivatives when the file has received a favourable
opinion from CTNBio (Brazil, 2005 Article 52).

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Table 3.2. List of Brazilian specific regulations for GE organisms.

Norm

Purpose

Advisory body
to which it
applies

Biosafety Law No.
11.105 of 03/24/05

Creation of the national biosafety
framework for genetically engineered
organisms.

CNB, CTNBio

Decree No. 5.591 of
11/22/05

For the implementation of the biosafety
law, creation of advisory bodies of the
regulatory system.

CNB, CTNBio

Decree No. 5950 of
10/31/06

Establishes limits for planting GEO in
areas bordering protected areas.
Designates Competent National
Decree No. 6925 of
Authorities and National Focal Points for
08/06/09
the application of Article 19 of the
Cartagena Protocol.
Provisional Measures Prohibition of planting GE plants in
from the President No. protected areas established in Law No.
327 of 10/31/06
9985 of 07/18/00.
CNBS Guideline No. 1 Gives capacity to CTNBio to authorize
of 07/31/08
commercial releases of GE organisms.
CNBS Guideline No. 2 Approves monitoring plan for GE
of 07/31/08
organisms and its derivatives.
Minister of Science
and Technology
Approves CTNBio Internal Regulation.
Ordinance No. 146 of
03/06/06
Minister of Science
and Technology
Modifies CTNBio Internal Regulation.
Ordinance No.373 of
06/07/11
CNBS Resolution No.
Approves CNBS Internal Regulation.
1 of 01/29/08
It disposes of installation and functioning
of the Biosafety Internal Commissions
CTNBio Normative
(CIBios) and of criteria and procedure for
Resolution No. 1 of
request, issue, review, extension,
06/20/06
suspension and cancelling of the
Biosafety Quality Certificate (CQB).
It disposes of risks classification of
CTNBio Normative
Genetically Modified Organisms (GMO)
Resolution No. 2 of
and biosafety levels to be applied to
11/27/06
activities and projects with GMO and its
derivatives in contention.
CTNBio Normative
It disposes of monitoring norms of
Resolution No. 3 of
genetically modified corn in commercial
08/16/07
use.

198

CNB, CTNBio

CNB, CTNBio

CNB, CTNBio
CTNBio
CTNBio

CTNBio

CTNBio

CNBS

CIBIos

CTNBio

CTNBio

Table 3.2. (cont’d).

CTNBio Normative
Resolution No. 4 of
08/16/07
CTNBio Normative
Resolution No. 5 of
03/12/08
CTNBio Normative
Resolution No. 6 of
11/06/08
CTNBio Normative
Resolution No. 7 of
04/27/09
CTNBio Normative
Resolution No. 8 of
07/03/09
CTNBio Normative
Instruction No. 2 of
09/10/96
CTNBio Normative
Instruction No. 4 of
12/19/96
CTNBio Normative
Instruction No. 8 of
07/09/97
CTNBio Normative
Instruction No. 9 of
10/10/97
CTNBio Normative
Instruction No. 13 of
06/01/98
CTNBio Normative
Instruction No. 17 of
11/17/98
CTNBio Normative
Instruction No. 18 of
12/15/98
CTNBio Normative
Instruction No. 19 of
04/19/00

It disposes of minimal distance between
the commercial cultivation of genetically
modified and non-genetically modified
corn, aiming at the coexistence between
the production systems.
Gives provisions on rules for commercial
release of Genetically Modified
Organisms and their derivatives.
Provides on rules for the planned release
to the environment of Genetically
Modified Organisms (GMO) of plant
origin and their derivatives.
Provides on rules for planned release into
the environment of Risk Class I
Genetically Modified Microorganisms
(GMM) and Genetically Modified
Animals (GMAn) and their derivatives.
Provides on simplified rules for Planned
Release into the environment of Risk
Class I Genetically Modified Organisms
(GMO) and their derivatives.

CTNBio

CTNBio

CTNBio

CTNBio

CTNBio

Provides rules for the import of GE plants
with research purposes.

CTNBio

Provides rules for transportation of GE
organisms.

CTNBio

Provides rules for genetic manipulation
and cloning of human beings.

CTNBio

Provides rules for genetic intervention on
human beings.

CTNBio

Provides rules for the import of GE
animals with research purposes.

CTNBio

Provides rules for the import, trade,
transport, storage, human/animal
consumption, environmental release and
disposal of products derived from GE
organisms.
Establishes conditions for the
environmental release of GE soybean
with herbicide tolerance (glyphosate)
including a monitoring plan.
Establishes the procedure for public
hearing by CTNBio
199

CTNBio

CTNBio

CTNBio

Table 3.2. (cont’d).
Communication
CTNBio No. 1 of
08/09/06
Communication
CTNBio No. 2 of
07/12/07

Communication
CTNBio No. 3 of
11/28/07

Communication
CTNBio No. 4 of
06/24/08

Communication
CTNBio No. 5 of
06/24/08

Communication
CTNBio No. 6 of
03/18/10
Communication
CTNBio No. 7 of
10/21/10

Establishes conditions of isolation for
authorization concession of planned
CTNBio
release in the environment of genetically
modified corn.
Establishes conditions of isolation for
authorization of planned release in the
CTNBio
environment of genetically modified
eucalyptus.
Authorizes stacked events with herbicide
tolerance and insect resistance derived
from Bacillus thuringiensis obtained by
conventional sexual crossing, to follow
the simplified norm in force,
CTNBio
in case there has already been analysis
and approval of research or planned
release with each of the events
independently.
Establishes conditions of isolation to
enable authorization of planned release to
CTNBio
the environment of genetically modified
cotton plant.
Authorizes Internal Biosafety
Commissions (CIBio) to authorize
activities of import, export and
CIBio
transportation of class 1risk GMO
derivatives for the sole use in research
under a regime of restraint.
Establishes conditions of isolation and
disposal to grant planned authorisation for
CTNBio
release into the environment of GE
soybean.
Establishes conditions of isolation and
disposal to grant planned authorisation for
CTNBio
release into the environment of GE sugar
cane.
Source: National Biosafety Technical Commission (CTNBio),
http://www.ctnbio.gov.br/index.php/content/view/55.html

The National Biosafety Technical Commission (CTNBio) is part of the Ministry of
Science and Technology. CTNBio is a consulting and deliberative, multidisciplinary
collegiate body that provides technical and advisory support to the Federal Government in the
formulation, updating and implementation of the National Biosafety Framework for GE
organisms and their derivatives (Brazil, 2005). CTNBio is composed of twenty-seven (27)
200

members, Brazilian citizens specialists of recognized technical and scientific knowledge from
different sectors (Table A3.1 in Appendix). From the 27 specialists, twelve are from
academia, nine from the Federal Government, and six represent the civil society. Of the
twelve specialists from academia, three are specialists on human health, three in animal
health, three in plants and three in environmental issues. Of the nine specialists from the
Federal Government there is one representative from each of the Ministries of: Science and
Technology, Agriculture and Supply, Health, Environment, Agrarian Development,
Development, Industry and Foreign Trade, Defense, Foreign Relations and of the Office of
the Special Secretary for Aquaculture and Fisheries of the Presidency of the Republic. Of the
six specialists that represent the civil society, there is one specialist from each of the
following areas: consumer rights, health, environment, biotechnology, family agriculture and
occupational health. The appointment of the above mentioned specialists is made by the
respective Minister of State (Brazil, 2005).
CTNBio acts by developing Technical Reports on a case-by-case basis on GE
organisms and its derivatives including security measures and restrictions if required by its
use. If the technical opinion has majority vote, the event is authorized. In case of appeals to
CTNBio’s commercial approvals, the National Biosafety Council (CNBS) makes the final
decision (Brazil, 2005 Article 52).
The Brazilian regulatory system also includes Registration and Monitoring Bodies
and Entities (OERF for its acronym in Spanish), formed from the respective registration and
monitoring bodies of the Ministries of Health, Agriculture and Supply, Environment and the
Office of the Special Secretary of Aquiculture and Fisheries of the Presidency of the
Republic. OERF’s members, within their respective jurisdictions, are responsible for the
compliance of CNBS deliberations and CTNBio’s technical decisions set up by Decree
5591/005 (Brazil, 2005).

201

For laboratory research activities with GE organisms, CTNBio issues a Biosafety
Quality Certificate (CQB). It is also the requirement for any institution committed to
education, scientific research, technological development and industrial production that uses
GE organisms, to set up an Internal Biosafety Commission (CIBio). CIBIO assigns a
principal technician in charge of each specific project to ensure that the research is conducted
in compliance with biosafety standards and measures established by CTNBio (Brazil, 2005,
2006).
The Biosafety Information System (SIB for its acronym in Spanish) is responsible for
managing the information resulting from the risk analyses, including authorization,
registration, monitoring and follow-up of activities involving GE organisms and their
derivatives (Brazil, 2005). The SIB is under the Office of the CTNBio Executive Secretary.

Comparison between the Brazilian and Uruguayan regulatory systems
The Brazilian regulatory system highlights the legal support developed for the
biosafety framework. Brazil has a National Biosafety Law and a vast number of regulations
for the Law’s implementation as observed in Table 3.2 In turn, the Brazilian regulatory
system has had the ability to modify rules in order to provide greater efficiency to the system
as the number of applications has increased.
Members of the National Biosafety Technical Commission (CTNBio) have changed
so that its members are now required to be recognized Brazilian citizens with doctoral degree
and an active professional career in biosafety, biotechnology, biology, human and animal
health or the environment. The Brazilian high scientific and professional capacity as well as
the strong political support for biotechnology, allowed the development of two transgenic
crops generated in Brazil, soybean with herbicide tolerance (Brazil, 2009) and bean with
virus resistance (Brazil, 2011).
202

A noteworthy feature of the Brazilian regulatory system is the broad participation of
stakeholders in the discussions along the decision-taking process. Changes in legislation to
make the system more efficient did not diminish public participation in the decision-taking
process. The Brazilian regulatory system performs public hearing carried out by CTNBio,
which is one of the public consultation mechanisms with the highest public participation.
Comparing the structure and operation of the Uruguayan regulatory system (chapter 2
of this thesis) with the Brazilian framework it seems that the Uruguayan advisory bodies:
Risk Assessment on Biosafety (ERB), Institutional Coordination Committee (CAI) and Ad
Hoc Groups corresponds with the Brazilian National Biosafety Technical Committee
(CTNBio) for the risk assessment phase. CTNBio like ERB/CAI/Ad Hoc Groups, performs
environmental security and food/feed safety analysis. However, the Uruguayan risk
assessment phase forwards the technical opinion to the risk management phase, while the
Brazilian CTNBio has the independence to approve applications either for research purposes
under contained conditions or deregulation for commercial release.
In Uruguay the Risk Management Commission (CGR) leads the risk analysis process
and is responsible for the risk assumed. Brazilian CTNBio seems to lead the risk analysis and
authorizations are based mainly on technical decisions. CTNBio may request socio-economic
analysis to the National Biosafety Council (CNBS), which corresponds to the Uruguayan
National Biosafety Cabinet (GNBio). The Uruguayan GNBio is composed of six Ministers
and the Brazilian CNBS is composed of eleven Ministers. Both are responsible for the
formulation and implementation of the national policy on biosafety. The Brazilian CNBS
may also perform socio-economic analysis if requested by CTNBio and gives the final
decision if a favourable CTNBio’s decision was appealed.
In Uruguay GNBio does not perform socio-economic analysis but issues resolutions
for authorizations. In Uruguay socio-economic analysis is always considered by CGR for

203

authorizations of deregulation. There is not an equivalent figure of the Uruguayan CGR in the
Brazilian regulatory system. The Brazilian CTNBio coordinates with the Brazilian
Registration and Monitoring Bodies and Entities (OERF) and the Biosafety Information
System (SIB), risk management tasks performed in Uruguay by CGR with regard to followup and control of authorized events and risk communication mechanisms, respectively.
The Brazilian criterion to consider as favourable a CTNBio’s technical opinion with
majority vote, would give efficiency to the Uruguayan regulatory system and could be
applied for field trials authorizations. The Uruguayan CGR could keep management tasks as
performed now regarding control of compliance of biosafety conditions.
In summary, in comparing their operations, both systems integrate environmental risk
assessment with food/feed safety analysis in a similar structure for the risk assessment phase
In the Brazilian system an approval of the CTNBio technical opinion by majority vote is
considered as a favourable decision, while in Uruguay the signature of six Ministers is
required and risk analysis is led by the risk management phase.

Description of the Paraguayan biosafety framework
Paraguay, like Argentina, has a mixed regulatory system based on existing regulations
for agriculture and has created GE specific norms. The existing regulations include the Law
No. 294/93 of Environmental Impact Assessment, the Law No. 2459/04 of the creation of the
National Service of Quality and Plant Health and Seeds (SENAVE), the Seeds Law No.
385/94 and the Law No. 2426/04 of the National Service of Animal Health (SENASA). With
regard to specific GE regulations, the Paraguayan biosafety framework is based on the
Decree No. 12,706/08 that modifies the Decree No. 18,481/97 that created the Biosafety
Commission (COMBIO) (Table 3.3). Under the former Decree No. 18,481/97, COMBIO had
the power to issue resolutions with regard to the authorization for the introduction, field trials
204

and commercial use of GE plants. The authorities that supported COMBIO resolutions,
within their respective jurisdictions, were the Ministries of Agriculture and Livestock (MAG)
and Health and Social Welfare.
The Paraguayan regulatory framework regulates GE plants (including trees) and
livestock products. In 2003 with the ratification of the Cartagena Protocol, a biosafety bill
was presented to Parliament that includes the whole range of GE organisms. Additionally two
proposals for a Biosafety Law, from the agricultural and green sectors respectively, were
submitted to Parliament (Personal Communication, 2010, Rojas, L. Coordinator of
COMBIO). The parliament has not yet enacted the biosafety bills. Meanwhile, the Decree
No. 18,481/97 was modified and expanded by the Decree No. 12,706/08. COMBIO is now
named the Agricultural and Forestry Biosafety Commission and the Decree No. 12,706/08
stipulates that the Ministry of Agriculture is the authority that issues authorization for the
different categories of uses based on COMBIO’s advisory body opinion (Paraguay, 1997,
2008).
But also, from 1997 to the ratification of the Cartagena Protocol in 2003, there were
specific GE resolutions issued from the Ministries of Agriculture and Health and rules set by
COMBIO that are summarized in Table 3.3 Administrative changes were implemented such
as the creation of the Secretary of Environment (SEAM), and changes in the Ministry of
Agriculture with the transition to independent agencies of Plant Health Services (SENAVE)
and Animal Health and Quality (SENACSA) and the Paraguayan Agricultural Technology
Institute (IPTA). A new decree, Decree No. 6733 of 06/13/11 has been recently approved,
that establishes the National Policy and Program of Agricultural Biotechnology and Forestry
of Paraguay (Paraguay, 2011)
COMBIO is a consulting and deliberative, multidisciplinary body that provides
technical and advisory support to the Ministers of Agriculture and Health. COMBIO issues

205

technical opinions with regard to the authorization for field trials and commercial use of GE
plants. COMBIO is composed of thirteen members, ten representing government institutions
and three from academia (Table 3.3). The government participants include eight
representatives of the Ministry of Agriculture, including three from the Secretary of
Environment, and one representative each from the Ministry of Health and the Ministry of
Industry. The academic representatives are from the National University of Asunción (UNA)
with one representative from the School of Agricultural Sciences, School of Veterinary
Science and one from the School of Natural Sciences. The final recommendation to the
Ministry of Agriculture in cases of commercial release is decided by majority vote, although
decisions to date have been reached by consensus.

Table 3.3. List of Paraguayan specific regulations for GE organisms.
Norm

Purpose

Decree No.
18481/97 of
09/18/97

Creation of the Biosafety Commission
(COMBIO)

Decree No.
12706/08 of
08/13/08

Advisory Body to
which it applies

Modifies Biosafety Commission (COMBIO)
(created by Decree No. 18481/97) for
Agricultural and Forestry Biosafety
Commission.

MAG Resolution
No. 376/09 of
06/30/09
MAG Resolution
No.2128/10 of
10/29/10
MAG Resolution
No. 158

Establishes the procedure to be followed by
field trial applications.

COMBIO

Modifies the procedures for field trial
applications not requiring the license of
environmental impact assessment.
Declares of Ministerial interest field trials for
research in biotechnology and biosafety.

Creates the Biotechnology Coordination at
SENAVE
SENAVE Resolution In item 282 is charged a fee for the risk
No. 555/10
analysis process.
Decree 6070/05

206

SENAVE

The Decree No. 12,706/08 separates the risk analysis of plants and trees from
livestock products. Thus, COMBIO has two secretariats, the Biotechnology Coordination,
created by the Decree No. 6070/05, of SENAVE that performs the risk analysis of plants,
while SENACSA performs risk analysis of livestock products. In turn, there is a subcommission subordinated to COMBIO specialized in risk analysis. COMBIO also can
request technical cooperation in national and international institutions with knowledge in
biosafety. For commercial release, in addition to the environmental risk analysis performed
by COMBIO, a license of environmental impact assessment must also be issued by the
Secretary of Environment in accordance with the framework of the Law No. 294/93.
The requirement of an environmental license was already in place for conventional
crops. The information reviewed is quite different for COMBIO and the Environmental
Impact Assessment performed by the Secretary of Environment but it is coordinated between
both authorities. COMBIO requests information specifically on environmental risk
assessment based on risk hypothesis while the Environmental Impact Assessment requests
the description of the project including information regarding the kind of activity whether
forestry, agriculture, etc.; the investment and the technology that the project implies; raw
materials and supplies; and waste volumes and treatments. It also requests a description of the
size of the area and whether the area includes features such as natural sources of water,
wetlands, or protected areas. It also requires a description of the vegetation and distance of
the area to populated areas. An analysis of environmental impact, mitigation measures and a
monitoring plan are also required according to SEAM Resolutions 368/08, 303/04 and
375/07. More details can be found in the Environmental Impact Assessment form called
Basic Environmental Questionnaire (CAB for its acronym in Spanish).
Figure 3.3 outlines the biosafety regulatory system of Paraguay. The specific advisory
bodies that compose the regulatory system and exclusively develop related tasks are indicated

207

in dark shading. Divisions that collaborate with the regulatory system in particular tasks are
indicated in light shading.

Figure 3.3. Scheme of the Paraguayan Biosafety Framework design. The specific advisory
bodies that compose the regulatory system and exclusively develop related tasks are indicated
in shading.

The Biotechnology Coordination (CB) at SENAVE receives the application form. CB
in the case of plants and trees and SENACSA in the case of livestock products, forward to
COMBIO a technical opinion as appropriate. Additionally, in the case of commercial releases
SEAM forwards to COMBIO the environmental license. A final recommendation is
forwarded by COMBIO to the Ministry of Agriculture.

208

Comparison between the Paraguayan and Uruguayan regulatory systems
The recently approved Decree No. 6733/11 establishing the National Policy and
Program in Agricultural Biotechnology and Forestry demonstrates the beginning of political
support in the area of agricultural biotechnology. The biosafety legislation in Paraguay covers
GE plants and GE livestock products while does not yet include microorganisms and animals
as in Uruguay. The Paraguayan biosafety framework is changing procedures to make the
system more efficient. For example, the fact that field trials do not require environmental
license accelerates the process.
Regarding the operation of the system, the Paraguayan COMBIO performs similar
tasks as the Uruguayan ERB committee and CGR commission. The Paraguayan COMBIO
commission performs coordination tasks for the risk assessment phase and participates in the
follow-up of authorized events as ERB does. But also it recommends biosafety policy and
forwards to the Ministry of Agriculture a recommendation whether to approve or not an
event. In Uruguay, the recommendation is performed by the Risk Management Commission
(CGR). In this sense, the Paraguayan system resembles the Argentinean biosafety framework
in which there is not a clear separation between risk assessment and risk management. The
Paraguayan regulatory system is also similar to the Argentinean one in that the signature of
the Ministry of Agriculture in Paraguay and the signature of the Secretariat of Agriculture in
Argentina is required for approval, while in Uruguay the signature of six Ministers is
required.

209

COMMON AND DISTINCT ELEMENTS FOUND ACROSS THE MERCOSUR
COUNTRIES
The comparative analysis provided in the following section is based on the description
of the respective regulatory systems derived from relevant government documents presented
in the previous section, and on opportunities for personal interaction with regulators from
each of the countries reviewed while I was working at the Uruguayan Biosafety Office. The
aspects compared include: legislative basis, regulatory triggers, methodology used for the
decision making process, structure and operation of the risk analysis process, composition of
the regulatory bodies, approaches to risk assessment, risk management and risk
communication, the requirement of post-market monitoring, and the average number of
applications submitted and events deregulated.
Table 3.4 indicates whether each of these aspects is similar or different among the
regulatory frameworks examined. The objective of identifying common and distinct
elements across the regulatory frameworks was to highlight practices that could be applied by
the Uruguayan’s regulatory system to improve its efficiency as well as to discuss aspects of
the risk analysis organization that could be approached regionally.
With regard to common elements found across the four countries examined, the basic
criteria for decision making regarding the use of GE organisms are shared among the
countries of MERCOSUR. This baseline of concepts includes the recognition that
biotechnology techniques per se are not inherently risky and so it is not the process itself
(biotechnology techniques) what has to be regulated but the product of biotechnology (ICSU,
2005). However, in the four countries analyzed, what triggers the regulation is the process of
genetic engineering. Products with the same traits but derived from conventional plant
breeding, selection, or accelerated mutagenesis are not required to go through the regulatory
systems.

210

Table 3.4. Common and different elements analyzed among the biosafety regulatory system of MERCOSUR countries.
Criteria of
comparison
Regulatory
triggers
Methodology
decision making
process

Argentina

Brazil

Paraguay

Uruguay

Process based
Risk analysis
Case by case
Step by step
Comparative approach using the concepts of familiarity and substantial equivalence
Risk factors for environmental and food safety evaluation
High influence on the final decision of the risk assessment result

Risk assessment
approach

Existing and GE specific new regulation
Legislative
basis

Structure and
operating of the
risk analysis
process

Biosafety bill in parliament
GE organisms used in agriculture
Cartagena Protocol (CP) signed

Biosafety law
GE organisms
CP ratified

Biosafety bill in parliament
GE plants and livestock products
CP ratified

Biosafety bill in preparation
GE plants.
CP ratified

See Table A3.1

See Table A3.1

See Table A3.1

See Table A3.1

211

Table 3.4. (cont’d).
Criteria of
comparison

Risk
management

Argentina

Partially independent from risk
assessment. Risk assessors also
perform risk manager’s tasks
Weight-of-evidence approach
Post-market monitoring not
required

Risk
communication

No procedures established.

Brazil

Paraguay

Partially
independent
from risk
assessment. Risk
assessors also
perform risk
manager’s tasks
Precautionary
principle and
Weight-ofevidence
approach
Post-market
monitoring
required
Procedures
established.
Request for
public comment
and public
hearing.

212

Uruguay

Partially independent from risk
assessment. Risk assessors also
perform risk manager’s tasks
Precautionary principle and
Weight-of-evidence approach.
Post-market monitoring not
required.

Independent from risk
assessment. Specific
commission for risk
management
Weight-of-evidence
approach. Precautionary
principle under discussion.
Post-market monitoring
currently not required.

Not currently defined

Procedures established.
Public notification and
request for public comment.

Another basic criterion is the use of the risk analysis methodology applying the
concepts of ‘case by case’ and ‘step by step’ (FAO, 2007) as well as the use of the
comparative approach with the traditional counterpart using the concepts of ‘familiarity’ and
‘substantial equivalence’ in the risk assessment (OECD, 1993). The risk factors considered
for the environmental and food safety evaluation are the same for each of the countries
reviewed. Consequently the information required in the application forms for the molecular
characterization, food safety as well as the biology of the plant and the environment where
the GE organism would be released, is basically the same among the countries examined
(FAO, 2007).
Generally within the countries examined, multidisciplinary and inter-institutional
commissions or committees give scientific and technical support and advice to the public
administration in the process of taking the final decision. In all cases, the authority with the
final decision has to take into consideration the technical opinion of the biosafety commission
regarding environmental and health risk assessment. These technical and scientific
commissions have a high degree of diversity in terms of the specialists that participate. In
Brazil the requirement to incorporate PhD-level accredited technicians or researchers
involved in GE disciplines, made a difference in terms of the commission efficiency, leading
to decrease in the average time for a commercial authorization from four to five years to one
to two years (Biosafety Law, Article 11, Brazil-CTNBio, 2005).
Regarding the legislative basis of the biosafety frameworks, in the four countries
analyzed, GE products must comply, and therefore the frameworks are supported in existing
regulations related to plant and animal protection, environmental legislation and seed
registration. In all cases, GE plants are under the norms applied in agriculture for
conventional crop counterparts. But also, in all four countries, technology specific regulations

213

were developed for the creation of advisory bodies and to establish conditions for release of
GE products.
Distinct elements were found across the regulatory frameworks with regard to the
legislative basis. Other differences were found in the structure and operation of the risk
analysis process, with respect to risk management approaches, risk communication
procedures and post-market monitoring requirements. A summary of the legislative basis and
the structure of the frameworks, regarding the main legislation, GE organisms regulated, the
authorities responsible for decision-making, and the number of members that compose the
different advisory bodies is presented in Table 3.5. Legislative differences are found in the
legal status, whether the frameworks are based on a resolution, decree or law level. Brazil is
the only country with a Biosafety Law in place (Brazil, 2005). Paraguay and Argentina have
presented to the Parliament a Biosafety Bill (Personal Communication, Rojas, L. Coordinator
of COMBIO, Paraguay, 2010; Personal Communication, Godoy P., General Director of the
Biotechnology Directorate of SAGYP, Argentina, 2010) and Uruguay is working on this
since the new regulatory system is being implemented (Uruguay, 2008).
As for GE organisms that are regulated by the different regulatory frameworks, there
is a gradual increase in coverage among the countries; currently Uruguay covers the fewest
GE organisms and Brazil the most. The current regulatory system in Uruguay covers GE
plants while Paraguay covers GE plants and livestock products. In Argentina the regulatory
system covers all GE organisms, i.e. plants, animals, microorganisms, and vaccines, but only
for use in agriculture, and in Brazil the regulatory system incorporates all GE organisms for
use in agriculture and medicine. Both Uruguay and Paraguay are working to increase the
scope of regulation. Uruguay has included all GE organisms in the biosafety bill currently
under development and all GE organisms are included in the bill that Paraguay has forward to
the Parliament.

214

Table 3.5. Comparative description of the regulatory systems of the MERCOSUR countries: Argentina (ARG), Brazil (BRA), Paraguay (PAR)
and Uruguay (URU).
Country

ARG

Framework
SAGyPA
Resolutions No
656/92,
39/03, 57/03,
644/03.
SENASA
Resolution
No.412/02

Particularities of
Risk analysis
Independent
administrative
route for
environmental
and food safety.

GE organisms
regulated

Plants
Animals
Microorganisms
Vaccines

Resolution issued by:
Authority
Firms
Secretariat of
Agriculture,
Livestock and
Fisheries
(SAGYP)
CNB

BRA

Law No.
11105/05
Decree No.
5591/05

Resolutions not
issued by a
Minister or
political entity.

Plants
Animals
Microorganisms
Vaccines

215

CTNBio

1

Risk analysis done by:
Advisory body Members
Government
CONABIA
Academia
(25 members)
Private
DNM
Government
(---)
CTAUOGM
(12 members)

Majority vote
Absolute
majority vote
and favorable
vote of at
least two
thirds of
members for
deliberations
on
commercial
approvals.

Government

CTNBIO
(27 members)

Government
Academia
Civil
Society

Table 3.5. (cont’d).
Country

PAR

URU

Framework
Decree No.
12706/08

Decree No.
353/008

Particularities of
Risk analysis
Environmental
impact evaluation

Independent
commissions for
risk assessment
and risk
management.

GE organisms
regulated
Plants
Livestock
products

Resolution issued by:
Authority
Firms
Ministry of
Agriculture
1
and Livestock
(MAG)

GNBio
composed of
the Ministers
of: MGAP,
MEF,
MVOTMA,
MSP, MIEM
and MRREE.

Plants

216

6

Risk analysis done by:
Advisory body Members
Government
COMBIO
Academia
(9 members)
Civil
Society
CGR
Government
(6 members)
ERB
Government
(1member)
Government
Academia
CAI
Non-state
(9 members)
public
entities
Government
Academia
Ad Hoc Groups
Non-state
(35 members)
public
entities

With regard to the Cartagena Protocol, Brazil and Paraguay ratified it in 2003 and
2004 respectively, while Uruguay recently ratified it (2011) and is in the three-month period
of the process for its entry into force (BCH website, 2013; Uruguay, 2011). Argentina has
instead only signed the Cartagena Protocol and so far there has not been political support for
its ratification (Argentina, 2000). The Protocol has obligations to fulfil when ratifying that
may help to harmonize the risk analysis procedures (Secretariat of the Convention on
Biological Diversity, 2000).
With respect to the institutional organization of the regulatory systems, in each of
these countries there are commissions or committees that address the assessment of risk to
human, animal and plant health, and the environment, but their structure and operation vary
from country to country. The Uruguayan framework seems to be the most complex in terms
of different authorities involved in the decision making, and the number of signatures
required for an authorization (Table 3.5). The complexity is observed in terms of
coordination and time consumed in the requirement of the six GNBio’s Ministers signatures
for the authorization of any of the categories of uses. In Argentina, if there are no objections
from CONABIA, CTAUOGM (SENASA) and DMA, the Secretariat of Agriculture
(SAGYP) makes the final decision whether to authorize the GMO or not (Figure 3.1). Only
one signature is also required in Paraguay, from the Ministry of Agriculture and Livestock
(MAG) who receives the opinion from COMBIO, SENAVE, SENACSA and SEAM as
appropriate (Figure 3.3). In the case of Brazil, the National Biosafety Technical Commission
(CTNBio) has the authority to decide regarding applications for research and commercial
release if there is a majority of votes.
Possibilities for Uruguay to positively impact the process efficiency would be to
reduce the number of authorities from GNBio required to sign the authorizations or to enable
the Risk Management Commission (CGR) to authorize contained field trials for research and

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cultivar registration purposes. GNBio has recently authorized CGR to renew future permits
for counter season seed production and research field trials (Uruguay, GNBio Resolution No.
46, 2012).
There is variation in the application review process among the different countries. In
Argentina the environmental and food/feed safety evaluations follow different administrative
routes. The applicant submits an application form at the office of the Biotechnology
Directorate with environmental information, at the office of SENASA with food and feed
safety information and at the office of Directorate of Agrifood Markets with economic
information (Figure 3.1). Another particularity of the Argentinean framework is that
delegates from industry (private sector), participate in the technical advisory commission (a
delegate cannot participate when an application is from the company he represents). Brazil
includes specialists representing the civil society as a distinct element compared to Argentina,
Paraguay and Uruguay. Brazil is the only country where the resolutions are issued by a
technical advisory body (CTNBio) and not by Ministers or political figures.
There is also lack of uniformity with respect to requirements for environmental impact
evaluation. Environmental legislation in Paraguay requires environmental impact evaluation
in addition to the environmental risk assessment performed by the advisory body COMBIO.
The environmental impact evaluation is performed in parallel by the Secretary of
Environment (SEAM). In Brazil, CTNBio also could request an environmental license, if it
considers the commercial use of a GE plant as a potential factor that degrades the
environment, but it is not mandatory as in Paraguay.
With regard to risk management, one difference indicated in Table 3.4 is the
independence of the risk management phase. In Uruguay there is a clear separation in
ERB/CAI vs GNBio/CGR performing the risk assessment phase and the risk management
phase, respectively. Except in Uruguayan where there is a specific commission for risk

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management with political delegates for advising ministers, in the other countries the risk
management is only partially independent from risk assessment. The Secretary of Agriculture
in Argentina, the Minister of Agriculture in Paraguay and the National Biosafety Council
(CNBS) of Brazil can be considered exclusively “risk managers”. However “risk assessors”
also perform risk manager’s tasks; thus they not only recommend approval of applications
based on environmental and health safety, but also determine risk management measures,
monitor compliance of biosafety conditions, and are responsible for the permits track.
Another difference indicated in Table 3.4 regarding risk management is the
consideration of the precautionary principle or a weight-of-evidence approach in the decision
making process. Argentina does not apply the precautionary principle in its regulatory system
and uses the International Standards for Phytosanitary Measures (ISPM) No. 11 as criteria for
risk analysis (FAO, 2009a). On the other hand, Brazil has incorporated the precautionary
principle in its Biosafety Law to guide the decision making process regarding environmental
risk (Brazil, 2005). Paraguay has incorporated the precautionary principle in the Biosafety
Bill presented to the Parliament. In Uruguay it is being discussed whether it would be
necessary to include the precautionary principle in the biosafety law. The precautionary
principle is already incorporated in the Uruguayan General Law of Environmental Protection
No. 17283 (Uruguay, 2000) and in the Law that ratifies the Convention on Biological
Diversity (CBD) No. 16408, (Uruguay, 1993). Besides, Uruguay recently ratified the
Cartagena Protocol. Although the Cartagena Protocol establishes a precautionary approach
that is more flexible than a principle, Uruguay enacted a specific law for the Cartagena
Protocol (Uruguay, 2011). These regulations will need to be coordinated with the biosafety
law.
As mentioned in the Literature Review of this thesis, the precautionary principle can
delay a decision based on hypothetical threats of harm even without evidence of occurrence

219

or negligible probability of occurrence (MacKenzie, 2000). The precautionary principle
orients the process of decision making, which is always subject to uncertainty (MacKenzie,
2000). It is worth mentioning that the Cartagena Protocol refers to the “precautionary
principle” as a “precautionary focus” that is more flexible than a principle. Besides the
Protocol includes the requirement of a risk assessment for the decision making, which limits
the application of precaution without any underlying basis. Generally within the
MERCOSUR countries a weight of evidence approach, rather than the precautionary
principle, is applied for the decision making (FAO, 2007). Thus, in the regulatory systems
that have included the precautionary principle, it is not influencing the dynamic of the risk
analysis. Table 3.6 shows the high number of events deregulated by Brazil in a short period
of time even with incorporation of the precautionary principle into its Biosafety Law.

Table 3.6. Average of applications approved per year in the period 1995-2013 by category of
use and country.

Country

Average of applications approved per year in the period
1995-2013 by category of use and country
Field trial

Total in the
period

Commercial (*)

Total in the
period

105 + 49.1

1790

1.6 + 1.8

28

Brazil

--- (**)

---

2.0 + 3.0

36

Paraguay

0 + 0.2

1

0.3 + 0.9

6

Uruguay

1.1 + 1.4

20

0.8 + 1.7

14

Argentina

(*) The “commercial” category includes also events approved as of March 2013
(**) Brazil data for field trials are not available.

The monitoring and control of the compliance of the biosafety conditions and
ordinances established for commercial use of GE organisms are administrated differently in
each country. In Argentina it is by the National Institute of Seeds (INASE) and SENASA
according to their respective responsibilities. In Brazil it is by existing agencies within the
220

public administration with those competences that form the Registration and Monitoring
Bodies and Entities (OERF), and in Paraguay by the Biotechnology Coordination, a specific
body created for this purpose within SENAVE. In Uruguay it is by existing bodies within the
ministries of the GNBio according to the risk management commission (CGR) ordinances
which to date include the General Directorate of Agricultural Services (DGSA) and the
National Institute of Seeds (INASE). Post-market monitoring has been required in Brazil
(Brazil, 1998, 2005, 2007, 2008) but recently was approved the possibility to ask for its
exemption (Brazil, 2011). It is being discussed its implementation in Uruguay and it is not
required in Argentina and Paraguay.
Regarding risk communication, Brazil and Uruguay have formal procedures
established. Argentina has not at this time set procedures for risk communication.
Regarding the average number of applications submitted and events deregulated in the
MERCOSUR countries, Tables 3.6 and 3.7 list the average number of applications submitted
in the last 17 years and the events deregulated in each country, respectively, as a way to
analyse the dynamic of each regulatory system. Figure 3.4 and 3.5 shows the accumulated
number and total number per year of commercial approvals over the period 1995-2011. With
regard to the number of applications approved per year for field trials, there is an asymmetry
comparing Argentina with Paraguay and Uruguay. Although data from Brazil was not
obtained, it is estimated that in Brazil the average number of approved applications for field
trials per year is similar to or higher than in Argentina.
Brazil is the country with the highest average number of applications approved for
commercial release per year (1.9), followed by Argentina (1.2) and then Uruguay (0.5) and
Paraguay (0.1). The average number of applications approved for commercial release in
Brazil has rapidly increased in the last three years as shown in Figures 3.4 and 3.5. Since
1997 Argentina has had a steady increase over time with an average between 0.8 and 1.2

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events approved per year. Argentina led with regard to the number of deregulated events until
2007, but was then surpassed by Brazil for number of approved events for commercial
release. Paraguay and Uruguay have maintained an average lower than 0.4 deregulated events
per year, with an increasing trend in Uruguay in the last two years.

Figure 3.4. Accumulated number of commercial approvals over the period from 1995-2011 in
MERCOSUR countries.

Both in Brazil and Uruguay the increase in the number of approvals coincides with
adjustments in the regulatory system. In Brazil it corresponds with the promulgation of the
Biosafety Law that re-structures CTNBio requiring to be comprised by experts with notable
scientific and technical learning that hold a doctorate degree and are currently active
professionals (Brasil, 2005). In the case of Uruguay the specific change that occurred around
the relevant year is the promulgation of the Decree 353/008 after the moratorium period
(Uruguay, 2008). As mentioned in first section of this chapter, Argentina has recently

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adjusted specific aspects of its regulatory system in order to improve its efficiency. Protocols
for counter season soybean seed production and field trials were adjusted. Also the way to
present the information by the applicant and criteria for the analysis of stacked events were
adjusted (Argentina, 2011).

Figure 3.5. Total number of commercial approvals per year in MERCOSUR countries from
1995 to 2011.

In Figure 3.5 is observed the unevenness among years and countries with a
concentration in the last five years. Brazil has the highest number of deregulated events with
a total of 32 followed by Argentina with 20 events. In a second level is Uruguay with eight
events approved for commercial release and then Paraguay with one event approved in
soybean. Brazilian political and economic support for biotechnology allowed this increased in
deregulated events and the development of the first national GE crop developed at the
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Brazilian Enterprise for Agricultural Research (EMBRAPA for its acronym in Portuguese), a
bean resistant to the golden mosaic virus approved in 2011 (Brazil, 2011).

Table 3.7. Events approved for commercial use (deregulated) by crop in the MERCOSUR
countries.

Crop

Event

Soybean
40-3-2
Soybean
MON89788XMON87701
Soybean
A2704-12
Soybean
A5547-127
Soybean
BPS-CV127-9
Total deregulated events in soybean
Corn
176
Corn
T25
Corn
MON810
Corn
BT11
Corn
NK603
Corn
GA21
Corn
TC1507
Corn
MIR162
Corn
MON89034
Corn
MON88017
Corn
BT11XGA21
Corn
MON810XNK603
Corn
TC1507XNK603
Corn
TC1507XMON810
Corn
MON89034XNK603
Corn
MON89034XMON88017
Corn
BT11XMIR162XGA21
MON89034XTC1507XNK6
Corn
03
Corn
TC1507XMON810XNK603
Total deregulated events in corn

Country
Paragua
Argentina Brazil
y









3
5
1






























Uruguay


1











14

224


17

0

7

Table 3.7. (cont’d).

Crop

Event

Cotton
MON531
Cotton
MON1445
Cotton
MON531XMON1445
Cotton
LLCOTTON25
Cotton
281
Cotton
MON15985
Cotton
GHB614
Cotton
T304-40XGHB119
Cotton
MON88913
Total deregulated events in cotton
Bean
EMBRAPA5.1
Total deregulated events in bean
TOTAL DEREGULATED EVENTS

Country
Paragua
Argentina Brazil
y













3
9
1

0
1
0
20
33
2

Uruguay

crop not
planted

--0
8

In summary, the general criteria used for the application of the risk analysis
methodology for genetically engineered crop technology as described for Uruguay in Chapter
2, are similar throughout MERCOSUR countries (FAO, 2007). Common elements are
observed mainly in risk assessment criteria and information requested in the application form
for environmental and food safety evaluation. The differences observed in risk assessment are
regarding who does it, how it is organized, what principles are followed. Major differences
among the regulatory systems are in structure and operation of aspects of risk management
and risk communication. While these differences could mean barriers for the possibility of a
regional system among MERCOSUR countries, the common elements found open an
opportunity for harmonization of procedures. The greater complexity of the Uruguayan
regulatory system with regard to its operation, results from the number of authorities required
for authorizations. Possible solutions emerged when comparing the national systems of
MERCOSUR countries.

225

REASONS FOR THE NEED OF HARMONIZATION AND ATTEMPTS THAT
HAVE BEEN MADE
Although similar in some ways, the different institutional organizations and
administrative procedures among the four countries analyzed, make it difficult to coordinate
the approval of GE organisms for commercial use in the region (GAHBA, 2008, 2009). There
are also different production, ecological, and socioeconomic conditions that cause growers to
have different interests or needs for GE crops and traits. The market’s size and dynamic also
can motivate different interests by the developers of the technology, and public opinion about
genetically modified organisms varies in the region. All this in part explains the asymmetric
number of events approved for commercial use among these countries (Table 3.7).
However, the regulatory system is a complex, long and expensive process.
Harmonization arises as a possible way to achieve a more efficient and effective framework
in the use of economic, infrastructure and human resources, eliminating at the same time
commercial problems of asynchronous authorizations (GHABA, 2009; OECD, 1995, 2012).
When an event is authorized in one country, several issues arise as a consequence since there
is an increased risk of low-level presence of non-authorized material (but approved in the
exporter country), which could restrict or even interrupt trade between countries. It may
reduce the offer of basic raw material for food or feed increasing the production costs.
Importation or cross border transfer of unapproved products, either unintended or intentional,
resulting in the illegal introduction of events as food, feed or seeds, may occur, especially
close to border areas. For these reasons, it is among the objectives of the MERCOSUR’s
countries to harmonize to the best of the possibilities, the biosafety regulatory systems
(MERCOSUR, 2003).
Harmonization, in the sense of “to accept mutually the authorizations among different
countries” while seeming an ideal situation, requires a high level of political, commercial and

226

risk analysis criteria coordination among nations. The European Union is an example of
harmonization at this level, an approach which has different layers of complexity. The
regional framework that is in place in the European Union (EU), dates back to 1990
(Directive 90/220/EEC). The EU system was built with the elaboration of new regulations
specific for genetically engineered organisms. The legislation is currently based on the GM
Food and Feed Regulation 1829/2003/EC that replaces the former regulation on novel food
No.258/97, on the Directive 2001/18/EC finished in 2002 that replaces Directive 90/220/EEC
of 1990 and on a series of Guidelines elaborated by the European Food Safety Authority
(EFSA) for risk assessment.
The European Commission (EC) that centralizes the operating system coordinating
with each EU Member State regulatory system was created by Directive 90/220/EEC. Each
EU Member State has its own regulatory system and therefore the Directive can have
different mechanisms and criteria for its implementation. The legislation establishes that any
EU Member State that receives an application for authorization of the use of a GE organism,
must forward the results of the initial risk assessment to the European Commission (EC).
From the EC the application is put under consideration to all EU Member States. If there are
objections or open questions regarding the initial assessment performed by the national
agency where the application was submitted, while the application is being reviewed by each
EU Member State regulatory system, EC consults with the scientific panel of the European
Food Safety Authority (EFSA) regarding food and feed safety and environmental risk as
appropriate according to the proposed use. Applications for environmental release can be
submitted, as explained above to a Member State national agency, or may be submitted
directly to EFSA.
EFSA was created in 2002 as the central European authority for the scientific
evaluation of food and feed safety (European Union Regulation 178/2002). EFSA is located

227

in Parma, Italy and operates separately from the European Commission. EFSA operates eight
scientific panels composed of independent scientist from different EU Member States. One of
these panels is the GMO panel with specialists on GE organisms and genetically modified
food and feed. The EFSA’s criteria for environmental risk assessment and food safety are the
same as those applied by MERCOSUR’s countries. Generally within the MERCOSUR´s
countries EFSA’s criteria are taken as a guide for risk assessment due to its scientific
robustness and because Europe is the destination of exports of many GM products.
EFSA’s scientific opinion is forwarded to the EC, which embraces other components
in its opinion such as political, socio-economic and cultural factors, taking the final decision.
If there are objections from any Member State, the application enters into a field of
exclusively political action involving the Regulatory Committee (RC) and the Council of
Ministers (CM). The EC forwards the application to the Regulatory Committee; it then moves
back and forth between the Regulatory Committee and the Council of Ministers until the
application is accepted, requiring 2/3 of votes, or it is rejected.
The complexity of the European regional system refers on the one side to the
coordination among Member States and on the other to the differences in the implementation
of the directive in each Member State (Ostrovsky et al., 2007). , Difficulties faced in the
linkage between the scientific opinion of the European Food Safety Authority (EFSA) and
the political opinion of the European Union executive body, i.e., the European Commission,
have obstructed the system, resulting in only two authorized events for cultivation at present,
insect resistance MON810 corn and EH92-527-1 potato with altered starch composition for
starch production (non-food) (COMPASS web site, 2011). Under the EU regulation, the
authorization licensed by the EC is valid in all Member States and can only be superimposed
in a specific country if it demonstrates a scientific reason to restrict its use. Thus, oppositions
to authorizations are disputed at the EC resulting in the deadlock of the system. As a way to

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unlock the flow of the system, a proposal from the European Commission is currently being
discussed in which countries that oppose an event would be able to ban it from cultivation on
non-scientific reasons.
In the countries of the Regional Trade Agreement MERCOSUR, the European level
of harmonization, although theoretically possible, is functionally impossible to achieve.
Several efforts have been implemented to analyze harmonization possibilities in the region
including: i) the creation of an Ad Hoc Working Group on Agricultural Biotechnology
(GAHBA) within the Agriculture Group No. 8 of Common Market Group of MERCOSUR;
ii) the creation of the Group No.5 on Public Policy in Biotechnology and Biosafety of the
Southern Agricultural Council (CAS), and iii) the project titled “Development of reference
tools for the risk management of biosafety in the expanded MERCOSUR” ( FAO
TCP/RLA/3109).
The GAHBA within the MERCOSUR had as terms of references: the evaluation and
elaboration of alternatives to harmonize and coordinate the biosafety regulatory systems as
well as norms related among the MERCOSUR’s countries (GAHBA, 2009). From the
diagnostic analysis performed and interchange of information, the general conclusion reached
by the Group was that there were practical limitations that make harmonization hard to
achieve at least in the short term (GAHBA, 2009). It was observed that it would be difficult
to harmonize the frameworks of each country in terms of their structure and operation, given
the different traditions in the regulation and national standards. Further complications arise
from the different agricultural, ecological, socio-economic and political situations of each
country. Companies that commercialize GE crops have different interest in each country’s
market, and farmers have different necessities and interests in GE products. In addition,
public perception as well as general response to change is different among the countries
examined (GAHBA, 2009).

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The GAHBA Group recommended that proposals for harmonization and coordination
should focus on actions aimed at the adoption of internationally recognized principles and
guidelines, in particular those for risk assessment, such as the Cartagena Protocol, Codex
Alimentarius and the International Convention for the Protection of Plant (item 1.3 of the
International Standard for Phytosanitary Measures No. 11). The GAHBA Group proposed
that each country apply its own criteria for the resolution of matters such as the structure of
the decision-making process and implementation of specific issues (GAHBA, 2007).
The Group No.5 (GT5) on Public Policy in Biotechnology and Biosafety of the
Southern Agricultural Council (CAS) was created in 2004 within the Coordination Network
for Agricultural Policies (REDPA for its acronym in Spanish). CAS is composed of the
Ministers of Agriculture of the MERCOSUR’s countries plus Bolivia and Chile, what is
called the “expanded MERCOSUR”. The technical administrative secretariat is performed by
the Inter-American Institute for Cooperation on Agriculture (IICA for its acronym in
Spanish). The terms of references for GT5 were not as specific with regard to harmonization
as were GAHBA’s. The objective of GT5 is to advise CAS’s Ministers on biotechnology
public policy. The GT5 has elaborated and maintained updated a publication with the
description of the Biosafety Regulatory Systems and status of commercial approvals in the
countries of CAS, the ‘expanded MERCOSUR’, (CAS, 2010) as an information source for
the analysis of harmonization possibilities. The basis for this publication was the information
gathered by GAHBA (GAHBA, 2007, 2008) and a questionnaire sent to the regulatory
offices asking regarding institutions involved in the regulatory system, requirements for
commercial authorizations, approach for risk assessment of stacked events and if the country
applies coexistence measures.
The aim of the FAO project was to discuss and reach regional agreed on minimum
reference criteria for the management of biosafety. Several workshops and courses where

230

carried out during this project. Two regional workshops, in Paraguay and Brazil, were
performed for the discussion and elaboration of a final document with agreed technical tools
and criteria for risk assessment and risk management. This document also includes a sample
of an application form (FAO, 2009b). The FAO final document, although useful to the
countries of the expanded MERCOSUR, has no binding power, leaving to each country´s
criterion its application and use. Uruguay used the FAO project’s final document for the
development of its own application form and discussion of criteria for risk assessment and
risk management, since at the time of the FAO project, Uruguay was at the beginning of the
process for the implementation of a new regulatory system. Other activities in the framework
of the FAO project included a regional workshop on biosafety research held in Argentina and
two courses, on introduction to risk assessment and risk communication held in Uruguay
(FAO project TCP/RLA/3109).
The GAHBA Group and the FAO project ended in 2009. The GT5 Group remains
active and its last meeting was in Paraguay last August (CAS, 2011). Although the GT5 does
not have specific objectives on harmonization, it is important that there is a group at a
regional level on biotechnology and biosafety. The fact that GT5 Group was created and is
being maintained demonstrates political interest for the matter in the region.

SUGGESTIONS FOR FURTHER PROGRESS TOWARDS A REGIONAL SYSTEM
While the above mentioned facts are bottlenecks to move towards a regional system,
other actions can be taken to reach harmonization, although not as extensive as for the EU
regulatory system. Harmonization could be reached for specific procedures to minimize the
consequences of the asymmetry. Three suggestions are proposed in this section with actions
toward harmonization while maintaining an effective and competent risk analysis process for
safe introduction of genetically engineered crops in each of the MERCOSUR’s countries.

231

The first suggestion is the re-establishment of the Ad Hoc Group in Agricultural
Biotechnology (GAHBA) that finished its tasks in 2009 (GAHBA, 2009). The second
suggestion has to do with the implementation of a regional advisory body for food and feed
safety assessment. The third suggestion is the creation of a coordinated system for field trials
as the “first and second phase” approach applied in Argentina.

Regional Ad hoc Group on agricultural biosafety of GE organisms
The Ad Hoc Group on Agricultural Biotechnology (GAHBA) was created within
Agriculture Group No. 8 of the Common Market Group of MERCOSUR. GAHBA was
comprised of regulators from the regulatory agencies of Argentina, Brazil and Paraguay. The
participants from Uruguay were from the Unit of International Affairs of the Ministry of
Agriculture, which participated with development of the biosafety framework. The richness
of GHABA was the qualifications of the individuals involved with regard to regulatory issues
and on the substance of the topics they dealt with. The documents elaborated by GHABA
helped to inform this analysis since they contain valuable information regarding the operation
of the regulatory systems that is not published or written in the legislation. At the regional
level, groups created from MERCOSUR have binding and mandatory force. Thus, the request
to conform the GAHBA group again, would create a regional qualified working group for the
discussion of the current agenda topics and elaboration of regional proposals, with the
eventual possibility of implementation in the countries of MERCOSUR.
The GT5 within the Southern Agricultural Council (CAS) is also a regional working
group for discussion. However, the elaboration of regional proposals for harmonization is not
an objective of GT5, and GT5 does not have mandatory force. Agreements signed by
Ministers at CAS have political and moral binding force but it does not mean that countries
will necessarily change their systems. On the other hand, if GHABA forwards a proposal of
232

harmonization that is accepted by the Common Market Group of MERCOSUR,
MERCOSUR’s countries have the obligation to incorporate the agreed upon harmonization
into each country’s legal system. This explains why GHABA acted with caution when
making recommendations on harmonization, since decisions by MERCOSUR require a
strong political will.
At the time that GAHBA was reviewing MERCOSUR’s countries’ regulatory systems
for harmonization, they had already independently developed biosafety policies according to
their particular national regulations, as well as agricultural, ecological, socioeconomic and
political situations. Although there are similar criteria, procedures and operation are
different, as described in previous sections, which led GHABA to conclude that
harmonization was functionally impossible to achieve (GHABA, 2009). However, GAHBA
recommended implementing a permanent mechanism of interchange of information,
interaction and mutual cooperation among the expanded MERCOSUR regulatory agencies as
a way to build confidence among authorities to move toward harmonization by joining efforts
of economic and technical/scientific human resources (GAHBA, 2009).
From the current agenda of the regulatory agencies, the issue of low level presence
and adventitious presence (that is related to coexistence) are urgent topics to approach
regionally. Low level presence refers to the necessity to establish tolerance limits for presence
of events that are not in the importing country but are approved in the exporting country.
Adventitious presence refers to the incidental, small amounts of approved GE material in
conventional commercial product (seed, feed, food) (SAA, 2010). There are currently no
standards in the region either for low level or adventitious presence. In May, 2010 there was a
specific Workshop on regional approaches to low level and adventitious presence organized
by the Seed Association of the Americas (SAA) in which the main conclusions, shared by
GAHBA (2009), were that zero tolerance is functionally impossible, and that it is necessary

233

to establish regional standards under international guidelines for risk assessment (SAA,
2010). In addition, the Working Group on Biotechnology of the Organization for Economic
Cooperation and Development (OECD), on Harmonization of Regulatory Oversight in
Biotechnology, is preparing a document with recommendations on how to proceed when a
low level presence situation happens.
On the other hand, adventitious presence is related to coexistence. Brazil has a
specific policy on coexistence that is under review (Brazil, 2007) and Uruguay is discussing
its implementation as was explained in chapter 2 of this thesis. There is a general regional
interest in coexistence manifested at the GT5 group of CAS (Personal Communication, Ing.
Agr. Benech E., Uruguayan representative at GT5 and president of the Uruguayan risk
management commission on biosafety (CGR), 2011).
These topics involve issues at a regional level justifying consideration by
MERCOSUR. These topics are being discussed individually in each MERCOSUR country,
but there is not yet a final decision, opening the opportunity for harmonization. Uruguay
could promote the request to re-convene the GAHBA group based on the knowledge that this
is an interest also for the other MERCOSUR countries (Personal Communication, GHABA’s
members from Argentina, Brazil and Paraguay (Godoy P., Cohelo M., Rojas L.,
respectively), 2010).
Uruguay took a first step toward creating a formal agreement between regulatory
systems, in this case with Chile. A formal agreement was established between the Uruguayan
and Chilean regulatory systems for interchange of information and mutual cooperation that is
already functioning (CGR, 2010). In the framework of this agreement there has been
interchange of information regarding biosafety protocols for winter seed production. A visit
of Uruguayan regulators to Chile was held in September 2011 in which winter seed
production facilities were observed with regard to biosafety conditions; regulatory procedures

234

also were discussed (CGR, 2011). Although the agreement with Chile is not about
harmonization, it is a first step toward harmonization feasibility. Mutual collaboration and
interchange of experience allow regulators to know each other regarding capacities, processes
and robustness of resolutions issued by each country. This agreement is being extended to the
other countries of the expanded MERCOSUR. The Ministry of Agriculture of Uruguay has
recently signed a memorandum of understanding with the Ministry of Agriculture of
Argentina, regarding sharing of information, capacity building and research in biosafety and
biotechnology (Uruguay, 2011).

Regional advisory body for food and feed safety assessment
International standards and trade require that decisions regarding food and feed safety
be based on solid scientific information. The criteria and information required by all
MERCOSUR’s countries for food and feed safety are the same, and follow the internationally
recognized guideline Codex Alimentarius (GAHBA, 2007, FAO, 2009b). This requirement
has led authorities to be aware of each country’s limitations in capacities and infrastructure
for risk assessment as well as the costs implied. From one side it is the necessity to enhance
human resources and capacities which could be regionally coordinated. Furthermore, it is also
the technical conviction that a regional approach is the right way to comply with the
information required with the necessary quality and efficiency.
Based on the above reasons it is proposed that a regional scientific and technical
committee or commission be created that could act as a regional advisory body regarding
food and feed safety of GE organisms. The structure and operation of this advisory body
could be discussed within the GAHBA group proposed in the previous item. A similar idea
was supported at the Workshop on research in biosafety organized in the framework of the
FAO project TCP/RLA/3109 (FAO, 2010) whose participants included regulators, scientists
235

from academia and research institutes and representatives from the governments of
MERCOSUR countries and Bolivia and Chile (was is called as the “expanded MERCOSUR).
Authorization for food and feed could be issued regionally independently from
authorization for planting, i.e. when an event is authorized in one country for all uses, it is
authorized in the other countries for food and feed, although restricted for cultivation. This is
a possible scenario since there are different interests in events among MERCOSUR’s
countries as explained above. This kind of split approval, recommended also by GAHBA
(2009), would allow an event to be authorized regionally for food and feed, but each country
to decide whether to approve it or not for planting. To be able to approve a GE plant for food
and feed but not for planting, would also eliminate the commercial troubles generated by the
asymmetric number of events that are approved for commercial use among MERCOSUR’s
countries (Table 3.7).
The European Food Safety Authority (EFSA) and the bi-national government agency
Food Standards Australia New Zealand (FSANZ) list requirements for GM food and controls
labeling that could provide examples from which MERCOSUR could develop a multicountry approach for harmonization. A regional agency for health risk assessment could be
created to enable events to obtain wide authorization in MERCOSUR for animal feed and
human consumption. This proposal has the challenges of defining a common application
form, at least regarding food and feed safety evolution, and strong political support from the
national health authorities to the suggested advisory body that would perform the safety
evaluations.

Regional coordinated system for contained field trials
Authorizations for commercial use take into account, apart from biosafety issues,
several other factors related to each country’s particular agricultural, ecological,
236

socioeconomic and political situation, making it impossible, at least in the short term, to
achieve harmonization with regard to commercial approvals. The proposal described in this
item refers to the possibility of coordinating at regional level contained field trials as a way to
synchronize future deregulations. The advantage of coordination for field trials lies in the
ability to make the risk assessment process more efficient and effective to save time, work
and money for regulatory systems, and to better coordinate product development for the
region by helping to avoid asynchronous approvals.
Although there are differences among regulatory systems in their structures and
operation, generally all of them adopt the same criteria for environmental risk assessment
(FAO, 2009b). Field trials for efficacy tests and environmental risk assessment could be
performed in the same time frame by MERCOSUR countries and information generated
could be shared. Consensus documents regarding plant biology and molecular
characterization could be used for risk assessment. Sharing of information could be
formalized regarding protocols of field trials for efficacy tests and for environmental risk
assessment. Biosafety protocols could be adjusted for each country as needed due to
different environmental conditions.
Based on the common elements used for environmental risk assessment, a regional
system for environmental risk assessment similar to the approach used by Argentina with
“first” and “second” phases of evaluation could be adopted. The “first phase” could be
coordinated regionally, while an eventual “second phase” of analysis for deregulation would
be performed individually by each country. A common system could be established for
contained field trials as a “first phase” of evaluation that includes efficacy tests as well as
parameters to test risk hypothesis that may arise in an eventual commercial release.
The field trials performed under the so called “first phase” of the Argentinean
regulation No.39/2003 are mainly trials to test the efficacy of the events. The efficacy of an

237

event is evaluated by looking at the agronomic performance, its commercial success and
whether varieties maintain market interest (Mihaliak, 2002). Trails are also performed to
provide information about factors that may influence environmental safety such as: vigor,
flowering time, root strength, weediness potential, and possible effects on non-target
organisms. Since agronomic and environmental safety parameters are highly influenced by
environment it is important to perform trials in each receiving environment. Thus, the “first
phase” would have two parts, one would be the original trial with a common protocol for
efficacy tests and additional biosafety parameters included as appropriate. The second part of
the first phase would be a review of information from the original trial to determine if there
are unanswered or environment specific questions needed for specific countries if the event
would move forward to the “second phase”.
A regional technical commission could coordinate the field trials of the “first phase”
and process the data. It could be possible to develop procedures and methodologies to assess
the environmental risk meeting national and international obligations, including the
Cartagena Protocol. Once an application is submitted to a national agency, it is forward to a
regional commission and to the rest of the MERCOSUR’s countries. The regional
commission would set a time frame for each country to issue the permit for field trials and to
define whether additional data is needed from local field trials to eventually authorize the
commercial use of the GE plant. The structure and operation of the regulatory system of each
country would remain the same, assuming they met regionally agreed upon standards.
The limitation of this proposal would be if an event were developed with a specific
trait for one country’s particular situation. In this case, field trials performed in countries
where there is no interest for an eventual commercial release, could be used to generate risk
safety information to approach the inconvenience of low level presence.

238

This approach, although incorporating a regional commission for the coordination of
the first phase evaluation, offers efficiency to the regulatory system, predictability to the
applicant and helps to increase the synchrony of commercial approvals among
MERCOSUR’s countries. Events that pass to a “second phase” of risk analysis could be
analyzed independently since each country will shape the final decision to its environment,
economic, politics, social and legal situation.

239

APPENDIX

240

APPENDIX

Table A3.1. List of institutions represented on the advisory bodies by country. The color code refers to the institution origin: government
( ), academia ( ), civil society ( ) and private sector ( )
INSTITUTIONS BY COUNTRY
ARGENTINA
Biotechnology Directorate
1 General Director
2 Technical Coordinator
3 Scientific Consultant on biosafety
4 Scientific Consultant on regulatory issues
CONABIA
1 National Institute of Agricultural Technology (INTA) of MAGYP, specialist in plants.
2 National Institute of Agricultural Technology (INTA) of MAGYP, specialist in animals and/or microorganisms.
3 National Council Scientific and Technical Research Ministry of Science, Technology and Innovation, specialist in plants.
4 National Council Scientific and Technical Research Ministry of Science, Technology and Innovation, specialist in animals and/or
microorganisms.
5 National Institute of Seeds (INASE), one representative from the Coordination of Special Projects on Biotechnology.
6 National Institute of Seeds (INASE) of MAGYP, one representative from the Laboratory of Molecular Markers.
7 National Health Service and Food Quality (SENASA). Specialists in plants.
8 National Health Service and Food Quality (SENASA), specialist in microorganisms.
9 National Health Service and Food Quality (SENASA), specialist in animals.
10 Secretariat of environment and sustainable development.
11 Secretary of Policies, Regulations and Health Relationships of the Ministry of Health.
12 National Institute for Fisheries Research and Development (INIDEP).
13 Biotechnology Office of SAGyPA (now corresponds to the Biotechnology Directorate of SAGYP), the General Director.
14 Biotechnology Office of SAGyPA (now corresponds to the Biotechnology Directorate of SAGYP), the Technical Coordinator.
15 University of Buenos Aires, College of Agriculture.

241

Table A3.1. (cont’d).
16 University of Buenos Aires, College of Natural Sciences.
17 National University of La Plata, College of Agriculture.
18 National University of La Plata, College of Science.
19 National University of Rosario. Specialist in areas related to biotechnology.
20 National University of Comahue. Specialist in areas related to biotechnology.
21 Argentine Association of Ecology (ASAE).
22 Argentine Forum of Biotechnology (FAB).
23 Biotechnology Committee of the Argentine Seed Association (ASA).
24 Chamber of Agricultural Health and Fertilizers (CASAFE).
25 Argentine Chamber of Industry of Veterinary (CAPROVE).
CTAUOGM of SENASA
1 National Health Service and Food Quality (SENASA)
2 Ministry of Health
3 National Council of Scientific and Technical Research (CONICET)
4 Food Area of the Secretariat of Agriculture, Livestock and Fisheries (SAGYP)
5 National Advisory Commission on Agricultural Biotechnology (CONABIA)
6 Academia
7 Food traders
8 Groups of Growers
9 Consumers Organizations.
10 Biotechnology Committee of the Argentine Seed Association (ASA).
11 Argentine Forum of Biotechnology (FAB).
12 Chamber of Food Products (COPAL)
DMA
--- Not specified, members of the office.

242

Table A3.1. (cont’d).
BRAZIL
CNBS
1 Minister of State Chief of the Civil House Office of the Presidency of the Republic (chairperson of CNBS),
2 Minister of State of Science and Technology
3 Minister of Agrarian Development,
4 Minister of Agriculture and Supply.
5 Minister of Justice.
6 Minister of Health.
7 Minister of Environment.
8 Minister of Development Industry and Foreign Trade.
9 Minister of Foreign Affairs.
10 Minister of Defense.
11 Special Secretary for Aquaculture and Fisheries of the Presidency of the Republic
CTNBio
1 Ministry of Science and Technology.
2 Ministry of Agriculture and Supply.
3 Ministry of Health.
4 Ministry of Environment.
5 Ministry of Agrarian Development.
6 Ministry of Development, Industry and Foreing Trade.
7 Ministry of Defense.
8 Ministry of Foreign Relations.
9 Office of the Special Secretary for Aquiculture and Fisheries of the Presidency of the Republic
10 Specialist on human health.
11 Specialist on human health.
12 Specialist on human health.
13 Specialists on animal health.
14 Specialists on animal health.
15 Specialists on animal health.
243

Table A3.1. (cont’d).
16
17
18
19
20
21
22
23
24
25
26
27

Specialists on plants.
Specialists on plants.
Specialists on plants.
Specialists on environmental issues.
Specialists on environmental issues.
Specialists on environmental issues.
Specialist on consumer rights.
Specialist on health.
Specialist on environment.
Specialist on biotechnology.
Specialist on family agriculture.
Specialist on occupational health.
PARAGUAY

COMBIO
1 Ministry of Agriculture and Livestock, National Service of Quality and Plant Health and Seeds (SENAVE)
2 Ministry of Agriculture and Livestock, National Service of Animal Health (SENACSA)
3 Ministry of Agriculture and Livestock, Secretary of Environment (SEAM), General Directorate of Environmental and Natural
Resources Quality Control (DGCCARN)
4 Ministry of Agriculture and Livestock, Secretary of Environment (SEAM), General Directorate of Biodiversity (DGB).
5 Ministry of Agriculture and Livestock, Secretary of Environment (SEAM), Directorate of Fisheries (DPE).
6 Ministry of Agriculture and Livestock, Paraguayan Institute of Agricultural Technology (IPTA)
7 Ministry of Agriculture and Livestock, General Directorate of Planning (DGP),
8 Ministry of Agriculture and Livestock, (SSEG)
9 Ministry of Health and Social Welfare, National Institute of Food and Nutrition (INAN).
10 Ministry of Industry and Commerce (MIC)
11 National University of Asunción (UNA), School of Agricultural Sciences (FCA).
12 National University of Asunción (UNA), School of Veterinary Science (FCV).
13 National University of Asunción (UNA), School of Natural Sciences (FACEN).

244

Table A3.1. (cont’d).
URUGUAY
CGR
1 Ministry of Livestock, Agriculture and Fisheries (MGAP)
2 Ministry of Economy and Finances (MEF)
3 Ministry of Housing, Land and Environment (MVOTMA)
4 Ministry of Public Health (MSP)
5 Ministry of Industry, Energy and Mining (MIEM)
6 Ministry of Foreign Relationships (MRREE)
ERB
1 Specialist in environmental risk assessment
2 Specialist in food/feed safety (to be incorporated)
CAI
1 Ministry of Housing, Land and Environment. Specialist in environment (MVOTMA).
2 Ministry of Public Health (MSP).
3 Ministry of Livestock, Agriculture and Fisheries (MGAP)
4 National Institute of Agriculture Research (INIA)
5 National Institute of Seeds (INASE)
6 Technological Laboratory of Uruguay (LATU)
7 Institute Pasteur of Montevideo (IP)
8 Biological Research Institute Clemente Estable (IIBCE)
9 University of the Republic (UDELAR)

245

Table A3.1. (cont’d).
Ad Hoc Groups
1
2
3
4
Molecular
5
Characterization
6
and
7
Identification
8
(GAHCIM)
9
10
11
12
13 Gene flow and
14 coexistence
15 (GAHFG)
16
17
18
19
20
21
22 Non-target
organisms
23 (GAHONOB)
24
25
26

1
2
3
4
5
6
7
8
9
10
11
12
1
2
3
4
5
6
7
8
9
1
2
3
4
5

National Institute of Agriculture Research (INIA), specialist on biotechnology
National Institute of Agriculture Research (INIA), specialist on molecular biology
National Institute of Agriculture Research (INIA), specialist on molecular biology
National Institute of Seeds (INASE), specialist on molecular identification.
Technological Laboratory of Uruguay (LATU), specialist on molecular identification.
Technological Laboratory of Uruguay (LATU), specialist on molecular identification.
Ministry of Livestock, Agriculture and Fisheries (MGAP), specialist on molecular identification.
Ministry of Livestock, Agriculture and Fisheries (MGAP), specialist on molecular identification.
Ministry of Livestock, Agriculture and Fisheries (MGAP), specialist on molecular identification.
University of the Republic (UDELAR), School of Agronomy, specialist on biotechnology.
University of the Republic (UDELAR), School of Science, specialist on molecular biology.
University of the Republic (UDELAR), School of Science, specialist on molecular biology.
Ministry of Housing, Land and Environment (MVOTMA), specialist on biodiversity
Ministry of Housing, Land and Environment (MVOTMA), specialist on biodiversity
Ministry of Housing, Land and Environment (MVOTMA), specialist on biodiversity
Ministry of Livestock, Agriculture and Fisheries (MGAP), Planning and Budget Office (OPYPA).
National Institute of Agriculture Research (INIA), specialist on crop biology.
National Institute of Agriculture Research (INIA), specialist on crop biology and physiology.
National Institute of Seeds (INASE), specialist on certified seed production.
University of the Republic (UDELAR), School of Agronomy, specialist on botany.
University of the Republic (UDELAR), School of Agronomy, specialist on crop biology.
Ministry of Housing, Land and Environment. Specialist in environment (MVOTMA), specialist on
biodiversity
National Institute of Agriculture Research (INIA), specialist on entomology.
National Institute of Agriculture Research (INIA), specialist on entomology.
National Institute of Agriculture Research (INIA), specialist on soil microorganisms.
University of the Republic (UDELAR), School of Agronomy, specialist on entomology.

246

Table A3.1. (cont’d).
27 Food/feed
28 safety
29 (GAHSHA)
30
31
32
33
34
35

1
2
3
4
5
6
7
8
9

Ministry of Public Health (MSP), specialist on human nutrition.
Ministry of Public Health (MSP), specialist on human nutrition.
Ministry of Public Health (MSP), specialist on human nutrition.
Institute Pasteur of Montevideo (IP), specialist on molecular biology.
Institute Pasteur of Montevideo (IP), specialist on genetically engineered animals.
National Institute of Agriculture Research (INIA), specialist on animal health.
Ministry of Housing, Land and Environment (MVOTMA), specialist on animal health and welfare.
University of the Republic (UDELAR), School of Medicine, specialist on human nutrition.
University of the Republic (UDELAR), School of Agronomy, specialist on animal health.

247

REFERENCES

248

REFERENCES

ARGENTINA. 1991. Creation of the National Advisory Commission on Agricultural
Biotechnology. SAGyPA Resolution No. 124/91 of 24th October, 1991.
http://www.minagri.gob.ar/site/agricultura/biotecnologia/20CONABIA/_archivos/creacion_conabia.pdf
__________. 1992. Application form for the authorization of genetically engineered
microorganisms and plants. SAGyPA Resolution No. 656/92 of 30th July, 1992.
http://www.minagri.gob.ar/site/agricultura/biotechnology/60APPLICATIONS/Res.%20GMM%20English.rtf
__________. 1993. Composition of the National Advisory Commission on Agricultural
Biotechnology (CONABIA). SAGyPA Resolution No. 669/93 of 08/23/93 that
modifies SAGyPA Resolution No. 124/91 of 24th October, 1991.
__________. 1997. Composition of the National Advisory Commission on Agricultural
Biotechnology (CONABIA). SAGyPA Resolution No. 328/97 of 05/20/97 that
modifies SAGyPA Resolutions No. 124/91 of 10/24/91 and 669/93 of 08/23/93.
__________. 2000. Signature of the Cartagena Protocol on Biosafety to the Convention on
Biological Diversity. 05/24/2000.
http://bch.cbd.int/about/countryprofile.shtml?country=ar
__________. 2002. Food safety of genetically modified organisms. SENASA Resolution No.
412/02.
__________. 2003a. Application form for the authorization of environmental release of
genetically engineered plants. SAGyPA Resolution No. 39/03 of 11st July, 2003 that
modifies Resolution No. 656/92 of 30th July, 1992 and derogates Resolutions No
289/97 of 05/07/97 and 131/98 of 10/26/98.
http://www.minagri.gob.ar/site/agricultura/biotechnology/60APPLICATIONS/Resolution%20Vegetables.doc
__________. 2003b. Application form for the authorization to experiment with and/or
release into the environment genetically modified animals. SAGyPA Resolution No.
57/03 of 18th July, 2003 http://www.minagri.gob.ar/site/agricultura/biotechnology/60APPLICATIONS/Resolucion%20GMAO%20English.doc
__________. 2003c. Regulation for genetically engineered corn seed production containing
events not authorized in Argentina for commercial use. SAGyPA Resolution No.
644/03.
__________. 2004. Creation of the Biosafety Office in the Secretariat of Agriculture,
Livestock, Fisheries and Food and modifications in the composition of the National
Advisory Commission on Agricultural Biotechnology (CONABIA). SAGyPA
Resolution No. 244/04 of 02/18/04.

249

__________. 2008. Composition of the National Advisory Commission on Agricultural
Biotechnology (CONABIA). SAGyPA Resolution No. 398/08 of 10/29/08 that
modifies SAGyPA Resolutions No 124/91 of 10/24/91, 669/93 of 08/23/93, 328/97 of
05/20/97 and 244/04 of 02/18/04.
http://www.infoleg.gov.ar/infolegInternet/anexos/145000-149999/146801/norma.htm
__________. 2008. Creation of the Biotechnology Directorate in the Secretariat of
Agriculture, Livestock, Fisheries and Food. Decree No. 1940/08 of 11/13/08.
__________. 2009. Creation of the Ministry of Agriculture, Livestock and Fisheries. National
Executive Power Decree No. 1365/2009 of 10/01/09 that modifies Decree No. 438/92
of 03/12/92 of Ministries Law.
__________. 2009. Creation of the Ministry of Agriculture, Livestock and Fisheries. National
Executive Power Decree No. 1366/2009 of 10/01/2009 that creates the Ministry of
Industry and the Ministry of Agriculture, Livestock and Fisheries modifying Decree
No. 357/2002 of 02/21/02 .
__________. 2010. Regulation for genetically engineered soybean seed production
containing events not authorized in Argentina for commercial use. SAGYP Resolution
No. 400/10 of 30 August, 2010.
http://www.minagri.gob.ar/site/agricultura/biotechnology/60APPLICATIONS/Res%20Soy%20Prod.doc (web link with non-official translation).
__________. 2011. Ministry of Agriculture, Resolution No. 701 of 10/27/11 derogates
SAGyPA Resolution No. 39/03 of 11st July, 2003 establishing new conditions and
procedures for the authorization of genetically modified organisms.
BIOSAFETY CLEARING HOUSE (BCH), Convention on Biological Diversity. 2013.
http://bch.cbd.int/
BRAZIL. 2005. Biosafety Law No.11105 of March 24th, 2005.
http://www.ctnbio.gov.br/index.php/content/view/12847.html
BRZIL. 2005. Decree No. 5591 of November 22nd, 2005 for the implementation of the
Biosafety Law No.11105 of March 24, 2005.
http://www.ctnbio.gov.br/index.php/content/view/12848.html
BRAZIL. National Biosafety Council (CNBS). 2008. Internal Regulation of the CNBS.
CNBS Resolution No. 01 of January 29th, 2008.
http://www.ctnbio.gov.br/index.php/content/view/12865.html
__________. 2008. Ratification of the Biosafety National Technical Commission (CTNBio)
Technical Opinion No. 987/2007 favorable to the commercial release of genetically
modified corn, event T25 or Liberty Link. CNBS Resolution No. 02 of March 5th, 2008.
BRAZIL. National Biosafety Technical Commission (CTNBio). 2006. CTNBio resolution
No.1 of June 20th, 2006. It disposes of installation and functioning of the Biosafety
Internal Commissions (CIBios) and of criteria and procedure for request, issue, review,
250

extension, suspension and cancelling of the Biosafety Quality Certificate (CQB).
http://www.ctnbio.gov.br/index.php/content/view/12861.html
__________. 2007. Resolution No. 3, 08/16/07. Monitoring norms of genetically modified
corn in commercial use. http://www.ctnbio.gov.br/index.php/content/view/12859.html
__________. 2007. Resolution No.4, 08/16/07. Disposition of minimal distance between the
commercial cultivation of genetically modified and non-genetically modified corn,
aiming at the coexistence between the production systems.
http://www.ctnbio.gov.br/index.php/content/view/12858.html
__________. 2008. Resolution No. 2, 07/31/08. Authorizes monitoring studies.
http://www.ctnbio.gov.br/index.php/content/view/12003.html
__________. 2009. Technical Opinion no. 2236/2009 of 10/12/09. Commercial Release of
Genetically Modified Soybean Tolerant to Herbicides of Chemical Class
Imidazolinones, Soybean CV127, Event BPS-CV127-9 2009.
__________ . 2011 Technical Opinion No. 3024/2011 - Commercial Release of genetically
modified bean resistant to Bean Golden Mosaic Virus (Bean golden mosaic virus BGMV), event Embrapa 5.1 - Case No. 01200.005161/2010-86.
http://www.ctnbio.gov.br/index.php/content/view/17813.html
__________. 2011. Resolution No. 9, 12/02/11. Monitoring norms of genetically modified
organisms post-commercial release.
http://www.ctnbio.gov.br/index.php/content/view/16781.html
CONSEJO AGROPECUARIO DEL SUR (CAS).2011. Website http://www.consejocas.org/
CONSEJO AGROPECUARIO DEL SUR (CAS). 2008. Biosafety Regulatory Systems and
Status of Commercial Approvals of Genetically Modified Organisms in the countries of
the Southern Agricultural Council. Working Group 5 on Public Policy in
Biotechnology and Biosafety, Coordination Network for Agricultural Policies
(REDPA), Southern Agricultural Council (CAS). 72p.
__________. 2010. Biosafety Regulatory Systems and Status of Commercial Approvals of
Genetically Modified Organisms in the countries of the Southern Agricultural Council.
Working Group 5 o) on Public Policy in Biotechnology and Biosafety, CAS/IICA- 2nd
ed-Santiago:IICA, CAS, Red de Coordinación de Políticas Agropecuarias (REDPA),
October 2010. 86p.
COMPASS.2011. http://www.gmo-compass.org/eng/gmo/db/
EUROPEAN COMMISSION. 2001. Directive 2001/18/EC of the European Parliament and
of the Council of 12 March 2001 on the deliberate release into the environment of
genetically modified organisms and repealing Council Directive 90/220/EEC.

251

__________. 2003a. Regulation (EC) 1829/2003 of the European Parliament and of the
Council of 22 September 2003 on genetically modified food and feed.
__________. 2003b. Regulation (EC) 1830/2003 of the European Parliament and of the
Council of 22 September 2003 concerning the traceability and labeling of genetically
modified organisms and the traceability of food and feed products produced from
genetically modified organisms" and amending Directive 2001/18/EC.
__________. 2004a. Commission Regulation (EC) 641/2004 of 6 April 2004 on detailed
rules for the implementation of Regulation (EC) 1829/2003 of the European Parliament
and of the Council as regards the application for the authorisation of new genetically
modified food and feed, the notification of existing products and adventitious or
technically unavoidable presence of genetically modified material which has benefited
from a favourable risk evaluation.
__________. 2004b. Commission Regulation (EC) 65/2004 of 14 January 2004 establishing a
system for the development and assignment of unique identifiers for genetically
modified organisms.
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS. (FAO).
2006. International Standards for Phytosanitary Measures ISPM No. 11. Pest risk
analysis for quarantine pests including analysis of environmental risks and living
modified organisms. Secretariat of the International Plant Protection Convention. FAO,
Roma.
__________. 2007. Instrumentos de la FAO sobre la bioseguridad (Biosecurity toolkit).
Roma, Italia. 148p.
__________. 2009a. Food safety assessment of genetically engineered food. Tools for
trainers. Food and Agriculture Organization of the United Nation, Rome, 201pp.
__________. 2009b. Regional Workshop on criteria for the management of biosafety.
Curitiba, Brazil, 23-24 March, 2009. In: FAO Regional Project TCP/RLA/3109 (D):
Development of technical reference tools for the management of biosafety in expanded
MERCOSUR countries.
GMO COMPASS. 2011.http://www.gmo-compass.org/eng/home/
Grupo Ad Hoc sobre Biotecnología Agropecuaria (GAHBA). 2007. VI Meeting of the Ad
Hoc Group in Agriculture Biotechnology. Acta 2/07, Montevideo, Uruguay, August.
__________. 2008. IX Meeting of the Ad Hoc Group in Agriculture Biotechnology. Acta
2/08, Buenos Aires, Argentina, May.
__________. 2009. XII Meeting of the Ad Hoc Group in Agriculture BiotechnologyMERCOSUR. Acta 1/09, Asunción, Paraguay, April.
INTERNATIONAL COUNCIL FOR SCIENCE (ICSU). 2005. Annual Report.
http://www.icsu.org/publications/annual-reports/annual-report-2005

252

MacKenzie DJ. 2000. International comparison of regulatory frameworks for food products
of biotechnology. Canadian Biotechnology Advisory Committee (CBAC). 62p.
MERCADO COMUN DEL SUR (MERCOSUR). 2003. MERCOSUR/LII GMC/DT No.
38/03. Creation of Ad Hoc Group in Agriculture Biotechnology.
Mihaliak CA. 2002. Preparing and conducting field testing: an industry perspective. In:
Proceedings of a Workshop on Criteria for field testing of plants with engineered
regulatory, metabolic, and signaling pathways, June 3-4, 2002, Washington DC, ed.
LLWolfenbarger. Blacksburg, VA: Information Systems for Biotechnology. pp. 57-61.
Nap JP, Metz PLJ, Escaler M and Conner AJ. 2003. The release of genetically modified crops
into the environment Part I. Overview of current status and regulations. The Plant
Journal 33:1–18.
ORGANIZATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT (OECD).
1993. Safety considerations for biotechnology: scale-up of crop plants. 43p.
__________. 1995. Harmonization of biotechnology regulation: Analysis of information
elements used in the assessment of certain products of modern biotechnology. OECD
Environment Monograph No. 100, Paris, France.
__________. 2012. Biotechnology Update. Internal Co-ordination Group for Biotechnology
(ICGB). No. 23, March 8, 2012.pp.5-6.
Ostrovosky AA. 2007. Up against a wall: Europe’s Options for Regulating Biotechnology
trough Regulatory Anarchy. European Law Journal 13(1)110-134.
PARAGUAY. 1997. Creation of the advisory Biosafety Commission (COMBIO) on
agricultural biotechnology. Decree No. 18,481/97 of September 18th, 1997.
__________. 2008. Decree No. 12,706/08 of August 13th, 2008 that modifies and expands
Decree No. 18,481/97 of the creation of the advisory Biosafety Commission
(COMBIO) on agricultural biotechnology.
__________. 2011. Decree No. 6733 of June 13th, 2011 for the establishment of the National
Policy and Program of Agricultural Biotechnology and Forestry of Paraguay.
SECRETARIAT OF THE CONVENTION ON BIOLOGICAL DIVERSITY. 2000.
Cartagena Protocol on Biosafety to the Convention on Biological Diversity: text and
annexes. Montreal: Secretariat of the Convention on Biological Diversity. 30p.
SEED ASSOCIATION OF THE AMERICAS (SAA). 2010. Seed movement in the
Americas. In: Workshop on Adventitious Presence and Low Level Presence, May 5-8,
Buenos Aires, Argentina. 26p. http://www.saaseed.org/site/?noindex
URUGUAY. 1993. Law No. 16,408 of 08/18/93 that approves the Convention on Biological
Diversity.
http://www.parlamento.gub.uy/leyes/AccesoTextoLey.asp?Ley=16408&Anchor=
253

URUGUAY. 2000b. General Environmental Protection Act No. 17283 of 11/28/00.
URUGUAY, MGAP-MVOTMA-MSP-MEF. 2008. Decree No. 353/008 of 07/21/08 on
biosafety of genetically engineered plants and its parts. Amending Decrees: No. 535 of
11/03/08 and No.280 of 06/08/09.
URUGUAY. 2011. Law No. 18,792 of August 3rd, 2011 that approves the Cartagena Protocol
on Biosafety to the Convention on Biological Diversity.
http://www.parlamento.gub.uy/htmlstat/pl/protocolos/prot-ap-37959.htm.
URUGUAY. 2011. Memorandum of understanding between the Minister of Livestock,
Agriculture and Fisheries of Uruguay and the Minister of Agriculture, Livestock and
Fisheries of Argentina. Article VII, regarding sharing of information, capacity building
and research in biosafety and biotechnology,08/02/11.
URUGUAY. 2010. Risk Management Commission (CGR). Minutes of meetings, 2010
URUGUAY. 2012. GNBio Resolution No. 46 that authorizes CGR to renew permits for
counter season seed production and research field trials.

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CHAPTER IV: APPLICATION OF THE PROBLEM FORMULATION APPROACH
WHEN ASSESSING ENVIRONMENTAL RISKS OF CROPS ENGINEERED WITH
COMPLEX TRAITS - A CASE STUDY OF DEHYDRATION STRESS TOLERANCE
IN CUCUMBER

INTRODUCTION
Crops engineered with complex traits such as dehydration stress tolerance, may utilize
genes for which the protein product is indirectly responsible for the desired phenotype. For
example, genes being used for the new traits may encode transcription factors that regulate
expression of other genes; they may code for signalling factors that initiate response to
perceived changes in the cellular environment; they may produce metabolic pathway
enzymes that result in the production of new cellular compounds, among others.
These sorts of genes have the potential to initiate a cascade of cellular changes and
thus may produce unanticipated effects on plant metabolism, physiology, and/or development
with biosafety implications. Adding to this complexity, the interaction between genotype and
the highly variable environmental conditions might affect the expression of the intended
phenotypes. As a result, the application review for environmental biosafety may be more
complex as we move from the first wave of genetically engineered crops, such as insect- or
herbicide tolerant crops for which the gene product directly confers the trait of interest, to
crops with more complex traits. It should be noted, however, that while important to
evaluate, the possibility of pleiotropic effects is not a hazard in itself. Rather, the same
ultimate harms must be evaluated, for example increased weediness or harmful effects on
non-target organisms, whether those harms arise due to primary effects of the gene, or
pleiotropic or unintended effects. While pleiotrophy means that there is a greater potential
for unintended effects to occur, unintended effects that do not result in a significant harm are

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not a regulatory concern. The regulatory system needs to adapt the risk assessment process
according to the dynamic of the technology, focusing on data that aids the decision-making
process. The objective of this chapter is to develop a conceptual framework for regulators
when analyzing environmental risk assessments of transgenic crops with complex traits. A
case study is performed for release of cucumber expressing the Arabidopsis thaliana
dehydration stress tolerance transcription factor gene, CBF, into the Uruguayan environment.
It is critical to ensure an effective risk assessment process by appropriately outlining
the Problem Formulation to define the right hazard and risk scenarios where harm could
happen. The roadmap begins with a list of possible harms that could occur as consequence of
cultivation of a specific GE crop. The list is refined by establishing an exposure pathway for
each harm with its corresponding testable risk hypotheses according to Raybould (2010).
The first stage to determine acceptance or rejection of these hypotheses is based on existing
data and baseline information. Those harms for which risk hypotheses can be sufficiently
corroborated by analyzing existing baseline information are eliminated from consideration.
For those harms for which it is necessary to obtain additional information, an analysis plan is
discussed. Biosafety parameters are discussed from a regulatory point of view in order to
contribute to the decision-making process of these soon-to-be-commercialized second
generation complex traits.

PROBLEM CONTEXT
The study case refers to cucumber plants that are genetically engineered for
dehydration-related environmental stress resistance using the CBF1 or CBF3 genes from
Arabidopsis thaliana. CBF genes encode members of the C-repeat binding factor (CBF) [also
termed DREB (dehydration-responsive element binding factor)] transcription factor family,
which induce expression of a set of abiotic stress-related genes (Jaglo-Ottosen et al., 1998;

256

Kasuga et al., 1999). Overexpression of CBF/DREB genes has led to enhanced freezing,
drought, and salt stress resistance (Jaglo-Ottosen, et al., 1998; Liu et al., 1998; Kasuga et al.,
1999; Gilmour et al., 2000). In this case study, Uruguay is considered as the receiving
environment where the GE cucumber plants would be released if a favorable regulatory
decision is issued. Figure 4.1 shows a schematic of the complex interplay of factors
influencing environmental safety considerations with respect to the case study.

Figure 4.1. Scheme of interconnection between factors that determine possible environmental
concerns: the crop, gene, trait and location of the study case (Schematic adapted from Grumet
et al., 2011).

According to the risk assessment methodology, the first step of risk assessment is the
identification of possible harms that the GE plant could cause to the environment. A list of
potential harms classified according to agronomic and ecological effects, compiled from
Ellstrand (2001), Dale et al. (2002), Conner et al. (2003), Snow et al. (2005), Chapman and
Burke (2006) and Craig et al. (2008), is presented in Table 4.1. The exercise to be performed
in Problem Formulation is to determine, for a specific combination of GE
plant/gene/trait/receiving environment (Figure 4.1), which potential harms could be
considered as real concerns and to postulate risk hypotheses to be tested relevant for decisionmaking.

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Table 4.1 Possible environmental harms that may require further consideration.
Possible environmental harms that may require further consideration
Weediness:
1)- GE crop itself becomes a weed in agricultural systems
(phenotypic effect of the gene causes volunteer plants with
increased persistence).
2)- Generation of more aggressive weedy relatives (harder to
kill, population expansion) due to gene flow from pollen.

Environmental biosafety issues

Agronomic

Commercial
issues

Ecological

Negative effects on organisms (non-target species and food
webs):
3)- Toxic effect of the gene product on non-target organisms.
4)- Harmful effect on organisms due to changes in
agricultural practices that may change the agroecological
system.
5)- Development of resistance to products that confer
herbicide or insect protection.
Negative effects on soil functions:
6)- Toxic effect of the gene product on soil microorganisms.
7)- Negative impact on soil physical properties and soil
microorganisms due to changes in agricultural practices.
Negative effects on natural resources (soil, water, wildlife
and flora) and its biodiversity:
8)- GE crop itself becomes an invasive species because it
could be more persistent.
9)- Gene flow from pollen to wild relatives causing one of
the following (implies hybridization and introgression
success of the transgene):
a) Increase abundance of wild relatives /become invasive
if transgene confers fitness advantage (population size);
b) Decrease abundance of rare wild relatives/become
extinct if it confer fitness disadvantage (outbreeding
depression) (loss of biodiversity) (population size);
10)- Harmful effect on non-target species (insects, natural
enemies, soil microorganisms):
11)- Soil degradation due to a change in agricultural
practices.
12)- Destruction of refuge areas due to agricultural expansion
over natural environments.

Negative effects on trade:
Coexistence 13)- Negative impact on trade due to gene flow from pollen
(adventitious to conventional or organic crop.
presence) 14)- Negative impact on trade due to seed mixing (seed
dispersal).

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The first step is to establish the problem context by: defining protection goals and the
environmental scope and analyzing baseline information regarding the GE crop, trait, gene
and receiving environment (Figure 4.1). These steps are discussed below according to the
Uruguayan biosafety framework.

Protection goals
Protection goals are defined based on the country’s law, statutes, regulations or
guidance (US EPA, 1998; Raybould, 2006; Raybould and Quemada, 2010; Wolt, et al., 2010;
Sanvido et al., 2012). Considering the study case to be released in Uruguay, protection goals
derive from the laws listed in Table 4.2 regarding the environment. Protection goals derived
from legislation include conservation and sustainable use of the biological diversity and
natural resources (air, soil, water, wildlife and flora), preservation of ecological protected
areas, and avoidance of invasive alien species.

Table 4.2. Uruguayan laws related to environmental protection.
Year
1935
1990
1993
1994

Law No.
9463
16112
16408
16466

2000

17283

2006

17942

2008
2011

18381
18792

Comments
Creation of the Ministry of Livestock, Agriculture and Fisheries.
Creation of the Ministry of Housing, Land and Environment
Ratification of the Convention on Biological Diversity
Declaration of national interest in environmental protection,
definition of environmental impact and prescription of
environmental impact studies for certain endeavors.
General Law of Environmental Protection passed. Establishes
specific considerations for living modified organisms.
Approval of FAO Treaty on genetic resources for food and
agriculture
Law of land and sustainable development passed.
Ratification of the Cartagena Protocol
Adapted from Uruguay, 2007

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Environmental scope
One of the criteria for environmental scope is whether environmental impacts of the
event itself will be analyzed, or whether impact of the associated technology will be
considered. In Uruguay the scope has been defined by the Risk Management Commission
(CGR) with the support of the National Biosafety Council (GNBio) that together perform the
risk management phase, to focus mainly on the event. The impact of the associated
technology is considered in a coordinated way between the regulatory system with the
respective government bodies with competence in the matter: the Division of Natural
Renewable Resources (RENARE) that has responsibility for soil conservation (considered as
a non-renewable natural resource) and Good Agricultural Practices (GAP) plans; the General
Directorate of Agricultural Services (DGSA) of the Ministry of Agriculture (MGAP); and the
National Directorate of Environment of the Ministry of Environment (MVOTMA). (See
Chapter 2 of this thesis for an example of integration of these divisions with the regulatory
system for commercial release authorizations).
Another criterion to be defined as part of the environmental scope is whether the event
is going to be analyzed in the context of the agroecosystem or more broadly in the wild
ecosystem. The focus in Uruguay has been defined to be the agroecosystem, but introducing,
when justified, parameters of the natural ecosystem (CGR, 2010). The small size of the
country determines that agriculture is carried out in close proximity to native areas and
environmental protection areas. In the case of abiotic stress tolerance traits, such as the study
case, it could be argued that it would be justified to not only include the agricultural
environment where the GE plant will be released, but also a wider environment including
semi-natural and natural environments where exposure to the new gene/trait could happen
either by gene flow or accidental release.

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In the case of Uruguay another criterion that frames the risk assessment is the political
definition established in Decree 353/008 to set coexistence between different production
systems (organic, conventional and transgenic). (See chapter 2 of this thesis for the progress
made on coexistence legislation). Coexistence rules and crop management measures are set to
regulate the planting of GE crops in order to avoid the unintended presence of GE material in
products obtained from other production systems for which trade markets does not allow GE
organisms. As mentioned in the previous section, coexistence does not refer to biosafety
issues; it refers to commercial issues to prevent potential economic losses. Scientific analysis
is required to assess its feasibility and to establish crop management measures to regulate the
coexistence.

Baseline information
The next step of problem formulation is to analyze the case-specific baseline
information. Although all potential harms listed in Table 4.1 fall within the defined protection
goals and environmental scope criteria, analysis of the baseline information regarding the
receiving environment and plant biology, indicates that not all potential harms are relevant
for the study case. In the following section is provided the evidence why concerns can be
eliminated from consideration and why others are required to be examined further. For each
potential harm listed in Table 4.1, the exposure pathway including specific steps that would
need to occur for the harm to happen, and the corresponding risk hypothesis, are described
according to Raybould (2010) (Table 1.10 from chapter 1 of this thesis). The risk hypothesis
postulated for each step of the pathway is formulated in a way that indicates that the
cultivation of GE cucumber crop will be harmless. If the hypothesis survives a rigorous
search trying to falsify it and the evidence actually corroborates it, the testing will have high
confidence showing that cultivation of GE cucumber is harmless (Raybould, 2010). Some of
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these hypotheses can be sufficiently corroborated by analyzing existing baseline information
and therefore the particular harm can be rejected early in Problem Formulation due to the low
probability of occurrence. For those risk hypotheses that it is necessary to find out additional
information an analysis plan is discussed.

PROBLEM DEFINITION
Agronomic harms related to weediness
Agronomic harm: The GE crop itself becomes a weed in agricultural systems
(harm 1).
The factor that determines this concern is the phenotypic effect of the gene product
that may cause volunteer plants with increased persistence. The protection goal (conservation
of the environment) is defined more concretely as the environmental value to avoid
weediness in agricultural fields. In other words, the environmental value to be protected is the
fact that the current cucumber crop (non-GE) is not weedy in agricultural fields. To evaluate
the risk of GE cucumber to become a weed, it is necessary to consider its crop biology and
reproductive characteristics, the phenotype that resulted from introduction of the CBF gene,
as well as conditions of the receiving environment and stress encountered (Ellstrand, 2001).
In this case, the exposure pathway or risk scenario that determines a real possibility
for the harm to occur would be if GE cucumber crop with dehydration stress tolerance is
deregulated and planted under conditions where lack of adequate moisture or salinity in the
soil or low temperature, is the main environmental factor limiting plant growth. Harm 1 is
discussed considering water stress condition as outlined in Table 4.3.
Dehydration stress tolerance is a trait expected to confer a fitness advantage to the GE
crop if the characteristic ‘dehydration stress’ currently limits crop growth (Hancock, 2003;
Chapman and Burke, 2006). In other words, in order for harm 1 to occur it is necessary that
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water stress conditions in the receiving environment are a major factor limiting plant growth.
Thus by conferring dehydration stress tolerance, the CBF gene, could release plant growth
from an environmental limitation, making GE cucumber plants able to grow and reproduce in
an environment in which they were previously not able to grow. GE cucumber plants may be
more competitive, increasing persistence and survival in the planting and nearby natural
areas, resulting in volunteer plants in subsequent crops, increasing weediness or invasiveness.
The broad risk hypothesis to test is that “transgene will not confer a selective advantage to
GE crop resulting in increased weediness or invasiveness”.

Table 4.3. Harm 1: Exposure pathway and risk hypotheses to characterize harm 1 of Table
4.1 regarding weediness in agricultural systems of the GE crop.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis



GE crop is not planted under lack
of soil moisture

GE cucumber crop is planted under
lack of soil moisture.
GE crop growth is not only limited
by water stress conditions.


GE cucumber crop growth is only
limited by water stress conditions.

GE crop does not leave viable seeds
in the field after harvest.


GE cucumber crop leaves viable
seeds in the field after harvest.

GE seeds do not survive winter
conditions.


GE cucumber seeds survive winter
conditions.

Volunteer plants do not complete
the life cycle and do not persist
more than one year.


Volunteer GE cucumber plants
complete their life cycle and persist
more than one year sufficient to
increase its weed potential in
agricultural systems (Harm).

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The first risk hypothesis of the exposure pathway to test is: ‘GE crop is not planted
under lack of soil moisture’. The evidence regarding characteristics of the receiving
environment indicates that in Uruguay cucumber crop is planted under field conditions with
irrigation and in greenhouses where water is also provided with no limitation (Uruguay,
2010, 2012a,b). However, a few growers at the south of the country occasionally can grow
cucumber under field conditions without irrigation and may have years of reduced moisture
(Personal Communication Ing. Agr. Luis Aldabe, Department of Crop Production, School of
Agronomy-UDELAR, 2012). The trait dehydration stress tolerance analyzed in the study case
may be useful for these growers that could plant cucumber under field conditions with water
stress or for those that apply irrigation and may avoid the cost of the irrigation system. Thus,
it is necessary to continue to risk hypothesis of step 2 of the exposure pathway.
The risk hypothesis of step 2 is ‘GE crop growth is not only limited by water stress
conditions’. The information needed to test this hypothesis is whether the crop management
practices typically address other possible growth limitations such as insect and disease
damage, physiological disorders, nutrient limitation, weed pressure, pollination requirements,
etc. Information regarding cultivation practices can be obtained from agronomists who work
and advise growers regarding the cultivation of cucumber. If the hypothesis is falsified by
corroborating that water stress condition is the main limitation, this means that the CBF gene
could release GE plants from that environmental limitation compared to non-GE plants and
the analysis requires advancing to step 3.
Evidence for crop management factors such as insect and disease control, fertilization
and weed control, indicates that these cultivation practices are not limiting cucumber
production in Uruguay (Aldabe, 2000). The main limitations to obtain a high yield of
cucumber production in Uruguay are lack or excess of water and low temperatures at the
beginning and end of the growing season (Aldabe, 2000). Cucumber can be grown on a

264

variety of soils, but it has to be fertile and well-drained (Gildemacher and Jansen, 1993).
Irrigation is required if the soil moisture is not maintained by appropriate rainfall, and it
cannot tolerate waterlogging (Purseglove, 1968, Tindall, 1983). Specifically, insufficient
irrigation results in low fruit quality due to poor fruit set that negatively affects seed
formation resulting in fruit defects as well as early maturation due to small fruit size (Aldabe,
2000). Additionally, lack of water increases the damage by powdery mildew (Erysiphe
cichoracearum and/or Spharotheca macularis) (Aldabe, 2000), which normally appears in
old senescent leaves. Therefore, information about cultural practices indicates that cucumber
crop growth in the receiving environment is mainly limited by water stress conditions. Thus,
the risk hypothesis 2 can be considered as false, necessitating progressing to step 3 of the
exposure pathway.
The risk hypothesis for step 3 is: ‘GE crop does not leave viable seeds in the field
after harvest’. Baseline information regarding the cucumber crop indicates that fruits that
remain in the field after harvest, are degraded in a few weeks and seeds released (Personal
Communication, Ing. Agr. Luis Aldabe, Department of Crop Production, School of
Agronomy-UDELAR, 2012). This evidence corroborates that cucumber crop may leave
viable seeds in the field after harvest falsifying hypothesis 3 of the exposure pathway and the
analysis advances to step 4.
The risk hypothesis to test step 4 is: ‘GE seeds do not survive winter conditions’.
Cucumber seeds have no dormancy mechanism and require protective conditions to survive
the winter (Purseglove, 1968; Bates et al., 1990). Cucumber plants are chilling sensitive and
need a warm climate with temperatures between 20°C and 30° C with frost-free conditions
for the entire growth period from sowing to harvest. The optimum day-night range of
temperature for growth is 30°C during the day and 18-21°C at night. Therefore, in cool
temperate countries it can be grown outside only during the summer months or year-round in

265

greenhouses (Gildemacher and Jansen, 1993; Tindall, 1983). The average temperature
according to data from the Agroclimatic Information System (GRAS) of INIA at
http://www.inia.org.uy/gras/) is below 15°C (Table 2 in Appendix). Local agronomists that
work with the cucumber crop in Uruguay agree based on personal observation, that although
fruits remain in the field after harvest, by the time seeds are mature and there is humidity in
the soil to germinate, the low temperature does not allow germination. The excess water in
the soil during winter for about five to six months degrades the seeds further eliminating the
possibility of seed over-wintering (Personal Communication, Ing. Agr. Luis Aldabe,
Department of Crop Production, School of Agronomy-UDELAR, 2012). This evidence
would block the exposure pathway on step 4 and harm 1 can be eliminated without further
consideration.

Agronomic harm: Gene flow from pollen to weedy relatives causing more
aggressive weedy relatives (harder to kill, population expansion) (harm 2)
The potential to cause more aggressive weedy relatives requires the occurrence of
gene flow from GE cucumber plants to compatible relatives. To evaluate the risk of gene
flow from GE pollen to weedy relatives it is necessary to first consider the baseline
information of the receiving environment regarding the origin and geographic distribution of
cucumber. Table 4.4 represents the pathways with the sequence of steps that are necessary to
happen in order for the cultivation of GE cucumber plants to cause agronomic harm 2.
The first condition is the presence of compatible, interfertile weedy relatives in the
receiving environment and so the first risk hypothesis of the exposure pathway is: ‘No
presence of weedy relatives in the receiving environment’. The evidence to look for to test
this hypothesis is the presence of compatible relatives in Uruguay.

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The analysis of the gene pool of cucumber (C. sativus L. var. sativus) and its related
species indicate that C. sativus L. var. sativus only produces fertile hybrids when crossed
with species from the subgenus Cucumis with the same basic chromosome number (x=7)
such as C.sativus L. (var. hardwickii) (Deakin et al., 1971; Puchalski and Robinson, 1990;
Gildemacher and Jansen, 1993; Bates and Robinson, 1995).

Table 4.4. Harm 2: Exposure pathway and risk hypotheses to characterize harm 2 of Table
4.1 regarding generation of more aggressive weedy relatives.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance
under lack of soil humidity

Hypothesis



No presence of weedy relatives in
the receiving environment

Presence of weedy relatives in
Uruguay

Pollen flow to weedy relatives

No pollen flow to weedy relatives
No hybridization between weedy
relatives and GE cucumber plants


Hybridization between the GE
cucumber plants and weedy
relatives

No hybrid survival and
reproduction


Hybrid survival and reproduction

No introgression of transgene into
weedy relatives


Introgression of CBF genes into
weedy relatives

Transgene does not confer a
selective advantage to hybrids


CBF genes confer dehydration
stress tolerance to weedy hybrids


Abundance of weedy hybrids is not
only limited by lack of soil
humidity

More aggressive weedy relatives
(harder to kill, population
expansion (Harm)

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The other species in the subgenus Cucumis, C. hystrix Chakr, is diploid 2n=24 and the
only successful interspecific hybridization between C. sativus L. and C. hystrix Chakr has
been obtained with the laboratory intervention of embryo rescue (Chen et al., 1997; Chen et
al., 2002). Backcrosses of the reciprocal F1 hybrids to either parent and self-crossing
indicated that the hybrids were male and female sterile (Chen et al., 1997). Attempts to obtain
hybrid plants between subgenera of Cucumis have not been successful. No hybrids have ever
been obtained in crosses between cucumber and any species of the subgenus Melo, even
when aided by embryo culture and/or other techniques (Bates and Robinson, 1995).
Cucumber (C.sativus var. sativus L) is native to India or southern Asia, probably
originating in the northwest of India (Bates et al., 1990). Cucumber (C. sativus L. var.
sativus) can be found native in temperate regions of Asia in the Arabian Peninsula (Oman
and Yemen), in Burma and China (Yunnan Province); in tropical areas of Asia, Sri Lanka,
Indo-China (Myanmar and Thailand) and in the Indian subcontinent. Its closest related
species, the wild C. sativus L. var. hardwickii, is not considered a weed and occurs only in its
center of origin (Gildemacher and Jansen, 1993) in temperate regions of Asia: China
(Guangxi, Guizhou, Yunnan), and in tropical regions of Asia: India (Nepal) (USDA-GRIN
online database).
In summary, according to the information provided above, there are no weedy
relatives and outcrossing to wild relatives would only be a consideration if the wild relative
C. hardwickii (Royle) Alef. coexists with GE cucumber plants (C.sativus var. sativus L.) in
the receiving environment. Considering Uruguay as the receiving environment, Uruguay is
located in the southeastern part of South America not being part of the center of origin of
cucumber (Cucumis sativus L.). In Uruguay there are no weedy relatives, wild relatives or
landraces of Cucumis sativus L. (Brussa, 2007; Lombardo, 1984; Zuloaga and Morrone,
1999). The existing baseline information regarding cucumber origin and geographic

268

distribution is sufficient to corroborate the risk hypotheses that there are no weedy or wild
relatives in Uruguay. Thus the exposure pathway of harm 2 is blocked in step 1 and can be
eliminated from consideration.

Agronomic harms related to a negative effect on organisms
Agronomic harm: The gene product is toxic to non-target organisms (harm 3)
The factor that determines this concern is the occurrence of a direct or indirect toxicity
effect of the gene product on non-target organisms. ‘Organisms’ in this context are globally
considered as non-target, since the trait introduced was not intended to have any toxic
properties i.e., does not have intended pesticide effect. A gene product could be toxic to
organisms due to molecular features and/or its mode of action. In the study case the gene
product (i.e., the CBF protein) is not the trait per se but the way to obtain the desired trait
(dehydration stress tolerance). Thus, not only a direct mechanism but a possible indirect
mechanism of the plant attribute (CBF genes) could change gene expression through
pleiotropic effects (unexpected secondary effects) ultimately resulting on an altered plant
metabolism with toxic effects on non-target organisms (Raybould et al., 2010). Therefore
these hypotheses require the analysis of molecular characteristics of the CBF protein as a
possible toxin per se, and the analysis of the proteins and other metabolic changes expressed
as result of its action. Table 4.5 represents the pathway with the sequence of steps that are
necessary to happen in order for the cultivation of GE cucumber plants to cause the
agronomic harm 3.
The first condition is that the gene product or metabolic changes caused by the gene
product are toxic to non-target organisms. The risk hypothesis to test is ‘the gene product or
metabolic changes are not toxic to non-target organisms’. First the gene product will be

269

analyzed and then possible metabolic changes. The first evidence to look for is whether the
CBF protein is toxic to non-target organisms.
Characteristics of the CBF protein that may help to evaluate its intrinsic hazard
include its physio-chemical and biochemical properties; biological function; mode of action
and source (Carlini and Grossi-de-Sa, 2001; Delaney et al., 2008). Physio-chemical and
biochemical properties refer to protein size, isoelectric point, stability to pH, temperature, and
chemical or biochemical agents. Structural characteristics refer to post-translational
modifications, amino acid sequence and secondary and tertiary structure which influence
mode of action at the molecular level and facilitate evaluation of the potential risk to nontarget organisms. These kinds of analyses are typically performed as part of the toxicity
review for food safety (FAO, 2007; Codex Alimentarius, 2003).

Table 4.5. Harm 3: Exposure pathway and risk hypotheses to characterize harm 3 of Table
4.1 regarding toxicity of the gene product on non-target organisms.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

The gene product or metabolic
changes resulting from the gene
product are not toxic to non-target
organisms.


The gene product or metabolic
changes are toxic to non-target
organisms (insects, soil
microorganisms or plants)

Severity of toxicity of the gene
product or metabolic changes does
not modify non-target organism
populations


Toxicity of gene product negatively
affects abundance of non-target
organisms (Harm)

For a protein to be a toxin it must be capable of causing disease due to contact with or
absorption by the organism’s tissues by interacting with biological macromolecules such as

270

enzymes or cellular receptors. A protein toxin could be related to a protein with enzymatic
activity, enzyme inhibition or binding certain nutrients causing anti-nutritive effects or acting
as carrier molecules, hormones or toxins that will bind to specific cell receptors and trigger a
reaction sequence ending in different possible toxic effects (Craig et al., 2008).
Plant toxic proteins that are thought to be involved in defense mechanisms include
lectins, ribosome-inactivating proteins (RIPs), inhibitors of proteolytic enzymes,
glycohydrolases, arcelins, chitinases, canatoxin and modified forms of storage proteins
(Carlini and Grossi, 2002 and references within it). CBF genes do not encode any of the
mentioned proteins. CBF genes encode members of the C-repeat binding factor (CBF) or
DREB (dehydration-responsive element binding factor) transcription factor family. The CBF
family is a small family of three transcriptional activators, CBF1 (Stockinger et al., 1997),
CBF2 and CBF3 (Gilmour et al., 1998; Medina et al., 1999), also identified as DREB1B,
DREB1C and DREB1A, respectively (Liu et al., 1998). The CBF proteins, and transcription
factors in general, have not been identified as toxins for plants, microorganisms or insects.
It is also possible that the insertion of the CBF gene and its promoter cause altered
expression of a native gene(s) that produces a toxin. Another possibility is that the insertion
disrupts a known plant gene or generates new open reading frames that could produce
unintended new proteins. These possibilities are evaluated by standard molecular
characterization of the transformation event that examines sequence integrity of the
introduced DNA as well as the region surrounding the insertion site to ensure that such
changes have not occurred.
The existing baseline information regarding CBF protein molecular characteristics
and mode of action is sufficient to corroborate the risk hypotheses that gene product is not
toxic to non-target organisms. Thus, the exposure pathway of harm 3 would be blocked in
step 1 and would be eliminated from consideration.

271

The second consideration is whether expression of CBF causes other transcriptional or
metabolic changes resulting in production of toxins by the plant. Transcription factors do not
generate different or new proteins but regulate time and amount of gene expression (Pabo and
Sauer, 1992; Riechmann et al., 2000; Hussain et al., 2011). Because CBF is a transcription
factor it may influence gene expression in such a way that it causes production of a toxin not
usually made under the circumstances.
The history of use (concept of familiarity) of cucumbers indicates that cucumber
plants may naturally produce toxins such as cucurbitacins (a secondary plant metabolite,
oxygenated tetracyclic triterpenoids) (Chambliss and Jones, 1966; Horie et al., 2007; Zehnder
et al., 1997). Thus, as part of normal food safety assays would be necessary to test for the
production of cucurbitacins. When the CBF genes are constitutively overexpressed in other
species several changes have been observed, many of which are associated with responses to
abiotic stress (Jaglo-Ottosen, et al., 1998; Liu et al., 1998; Kasuga et al., 1999; Gilmour et
al., 2000; Fowler and Thomashow, 2002; Chan et al., 2011); such as elevated levels of
proline, total sugars, catalase, and hydrogen peroxide (Hsieh et al., 2002a,b). In addition,
expression of abiotic stress related genes also is frequently associated with biotic stress
related genes, and so may influence expression of defense molecules (e.g., Little et al., 2009;
Atkinson and Urwin, 2012) and CBF overexpression has resulted in enhanced expression of
genes associated with response to biotic stimulus (Chan et al., 2011).
Overexpression of CBF has also shown growth retardation (dwarfing) in the absence
of stress and delayed reproductive development (Liu et al., 1998; Kasuga et al., 1999;
Gilmour et al., 2000; Achard et al., 2008). However, this seems to be related to a decrease in
the biosynthesis of the phytohormone gibberellin (GA) that targets DELLAs, a family of
nuclear growth-repressing proteins, for degradation (Achard et al., 2008). The resulting
growth restraint and late flowering should not be understood as a toxic effect due to the

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action of the proteins whose expression is regulated by CBF, but as a way to promote
survival under abiotic stress conditions (Achard et al., 2008).
Due to, the difficulty of predicting plant response to abiotic stresses and the
possibility of cross talk among stresses, an analysis plan is recommended to evaluate possible
unexpected secondary effects of CBF gene products in the releasing environment that would
result in toxic products that adversely affect non-target organisms. The analysis plan would
include comparative compositional analyses, performed as part of food safety, to determine
substantial equivalence between the GE crop and its conventional counterpart except for the
gene product introduced. In this study case, compositional data is relevant also for
environmental risk assessment since small molecules with potential toxic effects on nontarget organisms could be detected (Nickson, 2008). If there is a significant compositional
difference when comparing fruit samples, the analysis plan could extend compositional
analysis to leaves and roots in order to obtain more information before moving to field trials.
The analysis plan would include field trials if it is necessary to assess specific negative
impact on beneficial insects and/or soil microorganisms.

Agronomic harm: Negative effect on organisms due to changes in agricultural
practices (harm 4)
To evaluate whether possible changes in cultivation practices resulting from use of the
genetically engineered crop could lead to a harmful effect on non-target organisms, it is
necessary to analyze the baseline information regarding cultivation practices of cucumber
plants in Uruguay. Harm 4 generally has been considered with respect to herbicide-tolerant
GE crops that may increase the use of a specific chemical and thereby affect particular
beneficial organisms. While chemical use is not a factor for CBF crops, if efficacy tests
indicate that GE cucumber plants have drought tolerance to the point of not requiring
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irrigation, GE cucumber plants grown under field conditions may not be irrigated. If frost
tolerance is corroborated, the farmer would have the option of planting earlier in the spring or
harvest later in the fall coinciding with low temperature conditions and frosts. Table 4.6
represents the exposure pathway with the sequence of steps and the corresponding risk
hypothesis that are necessary in order for cultivation of GE cucumber plants to cause harm 4.

Table 4.6. Exposure pathway and risk hypotheses to characterize harm 4 of Table 4.1
regarding the GE crop to change cultivation practices that negatively affect the
agroecosystem.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

CBF gene does not confer
dehydration stress tolerance to GE
crop in the receiving environment.
CBF gene confers dehydration
stress tolerance to GE cucumber
plants under Uruguayan
environment.
There are no differences in
agricultural practices between the
GE crop and conventional crop.


There are differences in agricultural
practices between the GE cucumber
crop and conventional cucumber.

The change in agricultural practices
does not negatively affect nontarget organisms
The change in agricultural practices
negatively affects non-target
organisms (Harm).

The first condition in order for harm 4 to occur is that CBF gene confers dehydration
stress tolerance to GE cucumber plants under Uruguayan environmental conditions. The first
risk hypothesis of the exposure pathway to test is: ‘CBF gene does not confer dehydration
stress tolerance to GE crop in the receiving environment’. To test this hypothesis it is
necessary to evaluate the efficacy of the trait in the receiving environment. If it is
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corroborated that CBF gene under Uruguayan environmental conditions confers dehydration
stress tolerance, the analysis advances to step 2.
The second risk hypothesis of the exposure pathway to test is: ‘There are no
differences in agriculture practices between the GE crop and conventional crop’. The first
step here would be to determine the changes in agronomic practices that are likely according
to the performance of the CBF crop in the field. If CBF protects against some water stress
but does not eliminate need for irrigation completely, or would still be within range of
irrigation seen due to seasonal variation, can be considered as not causing changes in
agricultural practices and the exposure pathway be stopped at this step. If the levels of stress
tolerance conferred are sufficiently strong to cause significant changes in agriculture
practices, then the analysis is advanced to step 3.
The risk hypothesis to test in step 3 is: ‘The change in agriculture practices does not
negatively affect non-target organisms’. Changes such as modified irrigation regimes or
planting times are associated with agriculture in general, any crop that is planted and requires
irrigation or not, would have possible impacts on the agroecosystem. This is evaluated by the
ministry of environment when evaluates the environmental impact of agriculture in a
particular area but is not under the terms of references of risk analysis specific for the
biosafety of a GE crop. The question at hand is whether the changes that would occur as a
result of planting CBF cucumber is outside the range of normally observed agricultural
impacts. If not, the exposure pathway of harm 4 is blocked in step 3 and can be eliminated
from consideration. If novel agronomic changes result, for example, the cold tolerance results
in planting at a time when no other crops would be planted in the area, rather than simply
causing cucumbers to be planted earlier instead of an alternate crop that would have been
planted at that time, then a more detailed analysis of possible harms would be relevant.

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Agronomic harm: Development of resistance to products that confer herbicide or
insect protection (harm 5)
This risk is not relevant to CBF as it is not an insecticide or herbicide. There is also
no anticipated increase in use of a specific chemical. Table 4.7 represents the corresponding
exposure pathway with the sequence of steps and risk hypotheses that are necessary to
happen in order for the cultivation of GE cucumber plants to cause the agronomic harm 5.

Table 4.7. Exposure pathway and risk hypotheses to characterize agronomic harm 5 of Table
4.1 regarding resistance development to gene products that confer herbicide or insect
protection.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

No increased use of a specific
chemical product and/or adequate
management practices to avoid
resistance development.


Increased use of a specific chemical
product or inadequate resistance
management measures making
weeds/insects/disease to evolve
resistance to gene product or
chemicals being more difficult to
manage (Harm)

In order for harm 5 to occur there has to be a change in the crop management
practices regarding the use of chemical products. GE crops that constitutively express a
protein toxic to a specific insect may lead to insect resistance development to the particular
toxin. Similarly GE crops with herbicide tolerance increase the use of that specific herbicide
and may lead to weed resistance development to the particular herbicide. Resistance
development eliminates the GE crop technology and makes pest control management more
difficult. The evidence to look for to test the risk hypothesis is whether there will be an
adequate management to avoid resistance development or will be an increased use of a
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specific chemical product. In the case study the trait introduced is dehydration stress
tolerance rather than insect or viral resistance or herbicide tolerance. There is not expected to
be a change in agricultural practices regarding the use of chemical products. The exposure
pathway for harm 5 is blocked in the first step and therefore eliminated from consideration.

Agronomic harms related to a negative effect on soil functions
Agronomic harm: The gene product is toxic to soil microorganisms (harm 6)
The factor that determines this concern is the occurrence of a direct or indirect toxicity
effect of the gene product on organisms as was discussed for harm 3 (see page 269). This
harm shares the same exposure pathway and risk hypotheses as for harm 3 (Table 4.5).
Evidence provided is enough to corroborate that the CBF gene product per se does not have a
direct toxic effect on non-target organisms. However, as for harm 3, comparative
compositional analyses are relevant for environmental risk assessment to determine whether
there is a change in plant composition that can alter the ecological interactions of cucumber
plants with the biotic community.

Agronomic harm: Negative impact on soil physical properties and soil
microorganisms due to changes in agricultural practices (harm 7)
The factor that determines this concern is a possible change in cultivation practices,
specifically regarding tillage, that could lead to a harmful change in the soil ecosystem. This
harm shares the same exposure pathway and risk hypotheses as for harm 4 (see pages 273274, Table 4.6) but for the soil ecosystem (Table 4.8).

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Table 4.8. Exposure pathway and risk hypotheses to characterize harm 7 of Table 4.1
regarding the GE crop to change cultivation practices that negatively impact on soil physical
properties and soil microorganisms.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

There are no differences in tillage
practices between the GE crop and
conventional crop.
There are differences in tillage
practices between the GE crop and
conventional crop.


The change in tillage practice does
not negatively affects the soil
ecosystem.

The change in tillage practices
negatively affects the soil
ecosystem (Harm).

For this hypothesis testing it is necessary to analyze the technology and agricultural
practices applied for cucumber crops in Uruguay. Harm 7 has generally been considered
when examining the effect of no-tillage practices associated with herbicide tolerant GE
soybean. The traits conferred by CBF are not anticipated to influence tillage practices for
cucumber. The exposure pathway for harm 7 is blocked in the first step and therefore
eliminated from consideration.

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Ecological harms related to negative effects on natural resources
Ecological harm: The GE crop itself becomes an invasive species in natural
habitats (harm 8)
The factor that determines this ecological concern is the phenotypic effect of the gene
product that may cause volunteer plants with increased persistence, as was discussed for the
agronomic harm 1 (GE crop itself becomes a weed, see page 262). The environmental value
is to avoid invasiveness of alien species in natural habitats since cucumber is not currently an
invasive alien species in natural habitats of Uruguay. Similar to harm 1, to evaluate the risk of
GE cucumber to become invasive it is necessary to consider its crop biology and reproductive
characteristics, the phenotypic effect of the CBF gene introduced, as well as conditions of the
receiving environment and stress encountered (Ellstrand, 2001). In the case of the ecological
harm 8, it is expected the same phenotypic effect of the gene as in harm 1, that the trait
‘dehydration stress’ be able to change GE crop fitness under water stress conditions
becoming more persistent, expanding the range where GE cucumber plants could grow and
eventually invade in natural habitats.
The steps and hypotheses to test harm 8 are similar to those analyzed for harm 1.
Evidences from conventional cucumber plants indicate that seeds have no ability to survive
low temperatures and waterlogged winter conditions. The discussion of Harm 1 stopped in
step 4 since cucumber is not a weedy species and GE seeds would not survive winter
conditions requiring for survival warm temperatures, frost-free period as well as well
irrigated and drained soils (Bates et al., 1990; Gildemacher and Jansen, 1993). The exposure
pathway of harm 8 also stops at step 4 and can be eliminated from consideration without
further testing.

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Table 4.9. Exposure pathway and risk hypotheses to characterize harm 8 of Table 4.1
regarding the GE crop itself becoming an invasive species in natural habitats.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

Natural habitats have no lack of soil moisture.
Natural habitats have lack of soil
moisture.


GE plants growth in natural habitats is not
only limited by lack of soil moisture.

GE cucumber plants growth in
natural habitats is only limited by
water stress conditions.


GE crop does not leave viable seeds after
harvest in the crop field that is close to natural
habitats.

GE cucumber plants leave viable
seeds in the crop field that is close
to natural habitats.


GE seeds do not survive outside of
cultivation winter conditions in natural
habitats.

GE cucumber seeds survive outside
of cultivation winter conditions in
natural habitats.


Volunteer GE plants do not complete the life
cycle outside of cultivation and do not persist
more than one year in natural habitats.

Volunteer GE cucumber plants
complete the life cycle outside of
cultivation and persist more than
one year in natural habitats
increasing its invasive potential
(Harm).

Ecological harm: Gene flow from pollen to wild relatives causing one of the
following: wild relatives increase/become invasive or decrease abundance/extinct
(harm 9)
The factor that determines this concern is the occurrence of gene flow from GE
cucumber plants to compatible relatives such as in harm 2 (gene flow from GE pollen to
weedy relatives, see page 266). Similarly, to evaluate the risk of gene flow of GE pollen to
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wild relatives is necessary to consider the baseline information of the receiving environment
regarding the origin and geographic distribution of cucumber.
In order for the ecological harm 9 to occur, there must be compatible, interfertile wild
relatives in the vicinity of the GE cucumber crop (Tables 4.4 and 4.10). In the section
corresponding to harm 2 (page 266) are the reasons in detail providing the relevant known
and background information regarding the presence/absence of such relatives that allows
blocking the exposure pathway on step 1, eliminating this harm from consideration.

Table 4.10. Exposure pathway and risk hypotheses to characterize harm 9b of Table 4.1
regarding gene flow form pollen to wild relatives becoming invasive.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance
under lack of soil humidity

Hypothesis



No presence of wild relatives in the
receiving environment

Presence of wild relatives in
Uruguay

Pollen flow to wild relatives

No pollen flow to wild relatives
No hybridization between wild
relatives and GE cucumber plants


Hybridization between the GE
cucumber plants and wild relatives

No hybrid survival and
reproduction


Hybrid survival and reproduction

No introgression of transgene into
wild relatives


Introgression of CBF genes into
wild relatives


Transgene does not confer a
selective advantage to hybrids

CBF genes confer dehydration
stress tolerance to hybrids
Abundance of hybrids is not only
limited by lack of soil humidity


Increase abundance of wild
relatives/ become invasive (Harm)

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Ecological harm: The gene product is toxic to non-target species (insects and soil
microorganisms) (harm 10)
The factor that determines this concern is the possible toxic effect of the gene product
on non-target species, specifically in reference to the native environment, rather than the
agroecosystem. As discussed in harms 1 and 8 (pages 262 and 279 respectively), the crop
itself is not weedy and not likely to come in contact with the native environment.
Additionally the trait will not move into the native environment due to gene flow to wild
relatives as it was discussed in harms 2 and 9 relative to gene flow (pages 266 and 280
respectively). Thus, this harm can be eliminated from consideration without developing an
exposure pathway and risk hypotheses.

Ecological harm: Destruction of the natural resource soil due to a change in
cultural practices (harm 11)
Like in harm 10, as cucumber plants are not likely to come in contact with the native
environment and the trait will not move into the natural habitats due to gene flow to wild
relatives, then this harm can be eliminated from consideration without characterizing the
exposure pathway.

Ecological harm: Destruction of refuge areas due to agricultural expansion over
natural environments (harm 12)
The factor that determines this concern is an expansion of cucumber planting over
natural environments, specifically to native habitats currently not cultivated. To evaluate the
risk of agricultural expansion is necessary to consider whether the CBF trait would result in
planting cucumber in land that is currently not used for agriculture (e.g., dry or saline soils).
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Table 4.11 represents the exposure pathway with the sequence of steps that are necessary to
happen in order for the cultivation of GE cucumber plants to cause the agronomic harm 12.
The risk hypothesis to test is ‘the crop is not planted in large extensions or new
regions over natural environments’. The baseline information indicates that in Uruguay
cucumber is not among the main horticultural crops. There are no large cucumber producers
in Uruguay. It is planted in small areas under a crop rotation pattern traditional of the
horticultural system and in greenhouses in the north of Uruguay (Uruguay, 2000, 2010).

Table 4.11. Exposure pathway and risk hypotheses to characterize ecological harm 12 of
Table 4.1 regarding destruction of refuge areas due to agricultural expansion over natural
environments.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

The crop is not planted in large
extensions or new regions over
natural environments.


GE cucumber crop expanded over
natural environments destroying
habitats considered natural
protected areas (Harm).

Growers that produce tomato and pepper grow cucumber as a minor crop to
complement the production together with melon, beans and eggplant (Personal
Communication, Ing. Agr. Luis Aldabe, Department of Crop Production, School of
Agronomy-UDELAR, 2012). According to the last General Agricultural Census (2000) there
are 199 growers in the south of Uruguay with a total of 50 ha planted under field conditions,
and 71 growers in the north of Uruguay with a total of 3 ha planted in greenhouses (Table
4.12). A new General Agricultural Census has recently finished but the data is not yet
available (Uruguay, 2011). A recent partial horticultural survey indicates an increase in the
area planted in greenhouses in the north of the country to 4 ha with a total of 32 growers

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(Uruguay, 2010). This survey did not consider the area planted in the south of the country
under field conditions due to the small area. Agronomists specialized in horticulture agree
with a shift of the area planted of cucumber from the field to the north of the country in
greenhouses that allow a better control of its management (Personal communication, Ing.
Agr. Luis Aldabe, Department of Crop Production, School of Agronomy-UDELAR, 2012).
While dehydration stress tolerance will be interesting for growers, it is not expected to
result in an expansion of planting to the point of eliminating natural areas or to cause
cucumber to be planted in new regions where it would not have been planted before. Drought
tolerance would be useful for growers since makes the crop less dependent on irrigation but
would not expand the crop to natural areas with water stress. Cold tolerance also would be
useful by extending the growing period since low temperature and early frost of fall limits the
growing season. Additionally in the north of Uruguay where cucumber is produced in
greenhouses, salt tolerance would be useful to make cucumber plants less sensitive to
irrigation water with high content of salt (Personal Communication, Ing. Agr. Carlos Barros
and Luis Aldabe, Department of Crop Production, School of Agronomy-UDELAR, 2012).
Under greenhouse conditions the main source of water for irrigation is from water wells with
generally high content of dissolved salts (Zamalvide, 2000). This kind of water determines a
high conductivity in soils under greenhouse conditions since the rainfall does not reach the
soil to leach the excess of salt. This effect is greatly intensified by the high fertilization
generally applied with the irrigation in greenhouse production systems. However, under field
conditions the Uruguayan soils have no salinity problems. Soils are exposed to leaching of
salts by rainfall resulting in a low conductivity. Thus, the dehydration stress tolerance may be
valuable for growers both in the south of Uruguay under field conditions (to avoid irrigation
and expand growing season), and in the north under greenhouse conditions (to tolerate

284

salinity), but will not result in significant new production areas not used previously for this
crop.
On the other hand, a possible expansion of the crop due to an increased consumer
interest will depend on the market. There is a low demand in the Uruguayan market for
cucumber fruit since its consumption is low, mainly by immigrants and foreign people, not
being a vegetable of the Uruguayan diet (Personal Communication, Ing. Agr. Luis Aldabe,
Department of Crop Production, School of Agronomy-UDELAR, 2012). Additionally the
short postharvest life of its fruit makes it not well suited for export.
In summary, an expansion of the crop or its production in new areas is not expected.
Harm 12 regarding destruction of native areas due to planting expansion, can be ruled out
without further testing after corroborating the risk hypotheses ‘the crop is not planted in large
extensions or new regions over natural environments’, blocking step one of its exposure
pathway.
Table 4.12. Number of growers and area planted of cucumber crop in Uruguay.

Cucumber crop

Number of
growers

Under field conditions
(south of Uruguay)
In greenhouse
(north of Uruguay)

Area planted (ha)
Average per
Total
grower

199

50

0.25

71

3

0.04

Source: MGAP, General Agricultural Census, 2000

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Commercial harms related to negative effects on trade
Commercial harm: Negative economic impacts to conventional or organic crops
due to gene flow (harm 13)
This harm is related to the commercial situation of the cucumber crop in Uruguay.
The factor that determines the harm is the occurrence of adventitious presence of the
transgene in conventional and/or organic crops due to gene flow from GE cucumber pollen.
The protection goal related to this harm is the political definition of Uruguayan authorities to
allow coexistence among different production systems.
The concept of ‘gene flow’ in coexistence is different from the concept used in
environmental biosafety, for example in harms 2 and 9. In environmental biosafety ‘gene
flow’ is not harmful in itself, what is harmful is the phenotype that the transgene confers, for
example fitness enhancement that may lead in increase weediness (harm 2) or invasiveness
(harm 9) of the receiving plant. In coexistence, the presence of ‘gene flow’, per se, is defined
as the harm and not the effect of the gene. The biosafety consideration of gene flow on the
environment is evaluated first, before considering coexistence. Coexistence is analyzed once
the effect of the gene was considered harmless for the environment, otherwise the event
would not be authorized and there is no need to analyze coexistence.
Table 4.13 represents the pathway with the sequence of steps necessary to happen in
order for the cultivation of GE cucumber plants to cause agronomic harm 13. The general risk
hypothesis will be “transgene will not result in adventitious presence in conventional and/or
organic crops growing according to risk management measures for coexistence”.

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Table 4.13. Exposure pathway and risk hypotheses to characterize harm 13 of Table 4.1
regarding adventitious presence of the transgene in conventional and/or organic
crops due to gene flow.
Exposure pathway
Cultivation of GE cucumber plants
with dehydration stress tolerance.

Hypothesis

No presence of conventional or
organic crops in the receiving
environment.


Presence of conventional or organic
crops in the receiving environment
near enough one another to make
possible pollen exchange.

No gene flow from GE pollen to
conventional or organic crops.


Gene flow from GE cucumber
pollen to conventional or organic
crops (Harm).

The first step of the exposure pathway for harm 13 to occur is the intentional growing
of GE cucumber plants in fields where conventional or organic production systems are
present in the nearby area. As mentioned above, the cucumber crop in Uruguay is planted
under field conditions in the horticultural area of states at the south of Uruguay (Uruguay,
2000). The horticultural region is characterized by small fields one next to each other making
highly probable the presence of conventional and/or organic growers in the proximity of the
GE cucumber fields. Thus, the first risk hypothesis, ‘no presence of conventional or organic
crops in the receiving environment’, is falsified and the analysis goes to step two of the
exposure pathway.
The second risk hypothesis to test is: ‘there is no gene flow from GE pollen to
conventional or organic crops’. Since the mating system of cucumber is by cross-pollination
with honeybees as the main pollinating agent, which are able to transfer pollen up to three
kilometers (Dadant and Dadant, 1976; Root, 2005), if authorized, the GE cucumber crop
would likely be planted by horticultural growers that are concentrated in a small area next to

287

each other and step 2 of the risk scenario described above is probable (Hokanson et al.,
1997a, b).
Another factor to consider is environmental conditions. Collison (1973) described
conditions influencing pollen viability and bee activity in cucumber crops. Environmental
conditions directly influence pollination since bee activity, pollen viability and longevity as
well as flowering time and stigma receptivity are correlated each other and depend on
thresholds of temperature, light intensity, humidity and wind. Flowers (males and females)
open in the morning and normally close in the afternoon (evening) on the day of anthesis.
Bees foraging activity starts at the same time that anthesis occurs, triggered by the anther
dehiscence in staminate flowers and nectar secretion in pistillate flowers. Pollen is viable and
the stigmas are receptive once anther dehiscence occurs. Pollen longevity varies with the
variety and the environmental conditions, but generally decreases during the day and is
greatly reduced in day-old staminate flowers. Although it could be the case that the following
morning the petals of one day-old flowers are withered, the pollen may still be viable, the
pistillate flowers may contain some nectar and the stigma can be receptive. Environmental
conditions with low humidity and wind cause pollen to lose viability sooner. Stigma
receptivity also depends on environmental conditions but it remains receptive longer than
pollen viability. The conditions above described required for optimal flower formation,
anthesis, bee activity and pollination are met under the Uruguayan receiving environment
(Aldabe, 2000).
The other condition that must occur for GE pollen to effectively pollinate non-GE
plants is phenological overlap in flowering time. This would be probable since horticultural
growers from the same area sow crops according to climate conditions and market demand.
Thus, the second risk hypothesis is falsified corroborating the possibility for gene flow from
GE cucumber pollen to conventional or organic crops. Additional experimentation for

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hypothesis testing of this harm (Table 4.13) is not required. However, once a harm is
characterized as being possible to occur, the next step of risk assessment methodology is the
‘consideration of possible adequate strategies for the management of the risk, which could
reduce the probability of occurrence and/or its consequences and to meet contingencies’.
Therefore an analysis plan with experiments to find risk management measures to avoid
adventitious presence by cross pollination would be required according to Uruguayan
regulation of coexistence (Uruguay, 200)
An issue that has recently raised concern in the case of crops that are pollinated by
honeybees, is the prohibition by the European Union market of the importation of honey that
contains pollen from transgenic crops if the transgenic events are not authorized in the
European Union for all categories of food and feed (Uruguay, 2012-2013). This new market
situation has already damaged the honey production in Uruguay due to the presence of pollen
from GE corn containing the event MON810 as well as other countries for which main honey
market is Europe. Similar to the risk management approaches for corn that is wind
pollinated, discussions are underway regarding the location of beehives. It is proposed that
beehives from which honey is going to be exported be at least ten kilometers from any GE
crop. However in the study case, cucumber requires honeybees for its normal pollination and
therefore it will be necessary to locate beehives in the crop and make sure the honey is not
exported to Europe.

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Commercial harm: Negative economic impacts to conventional or organic crops
due to seed mixing (harm 14)
In this case the factor that determines the harm is the occurrence of adventitious
presence of the transgene in conventional and/or organic crops due to seed mixing. Table
4.14 represents the pathway with the sequence of steps that are necessary to happen in order
for the cultivation of GE cucumber plants to cause the agronomic harm 14.

Table 4.14. Exposure pathway and risk hypotheses to characterize harm 14 of Table 4.1
regarding adventitious presence of the transgene in conventional and/or organic crops due to
seed mixing.
Exposure pathway
Hypothesis
Seed production of GE cucumber
plants with dehydration stress
tolerance.
No seed production of conventional
or organic cucumber in the

receiving environment.
Seed production of conventional or
organic crops in the receiving
environment.
No seed mixing of GE seed in
conventional or organic cucumber

seed production.
Seed mixing from GE cucumber
seed to conventional or organic
cucumber seed production (Harm).

The exposure pathway described in Table 4.14 is blocked in step 1 since there is no
cucumber seed production in Uruguay at the commercial level [(Personal Communication,
Sanguinetti G., Seed certification manager of the National Seeds Institute (INASE), 2012].
Thus, harm 14 is eliminated from consideration of the study case.

290

SUMMARY OF PROBLEM FORMULATION

The roadmap began with a list of possible environmental harms that could occur as
consequence of cultivation of GE crops. The list was refined by analyzing the exposure
pathway and corresponding risk hypotheses using existing data and baseline information.
Those harms for which risk hypotheses were sufficiently corroborated were eliminated from
consideration. Table 4.15 shows the original table (Table 4.1) with the harms that require
further analysis highlighted in bold black and the harms eliminated in normal black.
In summary, harms that require further considerations in the study case include
concerns related to a negative impact on non-target organisms such as beneficial insects
and/or soil microorganisms of the agroecosystem that may result from secondary effects of
expression of CBF leading to increased production of natural toxic products in cucumber
(harms 3 and 6 respectively). This consideration can be evaluated by testing for substantial
equivalence and levels of known cucumber toxins. The harm caused by the hazard associated
with the commercial situation of potential adventitious presence due to gene flow from GE
cucumber pollen to conventional and/or organic crops (harm 13), is also relevant for the
study case and requires further considerations. According to the Uruguayan legislation it
would be necessary the implementation of management measures to prevent adventitious
presence.
If harm requires further consideration an analysis plan is elaborated describing the
experimental design, assessment endpoints and methodology to measure them. Table 4.16
summarizes the process of Problem Context and Problem Definition with respect to the
harms defined as relevant for the study case.
In conclusion, the list of potential environmental harms to be considered, which is
based on environmental protection goals and scope, would be the same either for genes with
direct effects, such as insect- herbicide tolerant crops, or for genes conferring more complex
291

traits such as the study case of an abiotic stress tolerant crop. A difference with respect to
analysis of traits that may confer a selective advantage in the receiving environment and/or
the use of genes whose products regulate the expression of other genes, is the necessity to
consider potential for a broader range of possible phenotypes that could cause environmental
impact.

292

Table 4.15. Possible environmental harms that may require further consideration.

Environmental biosafety issues

Possible environmental harms that may require further consideration
Weediness:
1)- GE crop itself becomes a weed in agricultural systems
(phenotypic effect of the gene causes volunteer plants with
increased persistence).
2)- Generation of more aggressive weedy relatives (harder to kill,
population expansion) due to gene flow from pollen.
Negative effects on organisms (non-target species and food
webs):
Agronomic 3)- Toxic effect of the gene product on non-target organisms.
4)- Harmful effect on organisms due to changes in agricultural
practices that may change the agroecological system.
5)- Development of resistance to products that confer herbicide or
insect protection.
Negative effects on soil functions:
6)- Toxic effect of the gene product on soil microorganisms.
7)- Negative impact on soil physical properties and soil
microorganisms due to changes in agricultural practices.

Commercial
issues

Ecological

Negative effects on natural resources (soil, water, wildlife and
flora) and its biodiversity: 8)- GE crop itself becomes an invasive
species because it could be more persistent.
9)- Gene flow from pollen to wild relatives causing one of the
following (implies hybridization and introgression success of the
transgene):
a) Increase abundance of wild relatives /become invasive if
transgene confers fitness advantage (population size);
b) Decrease abundance of rare wild relatives/become extinct if
it confer fitness disadvantage (outbreeding depression) (loss
of biodiversity) (population size);
10)- Harmful effect on non-target species (insects, natural
enemies, soil microorganisms)
11)- Soil degradation due to a change in agricultural practices.
12)- Destruction of refuge areas due to agricultural expansion
over natural environments.

Negative effects on trade:
Coexistence
13)- Negative impact on trade due to gene flow from pollen to
(adventitious
conventional or organic crop.
presence)
14)- Negative impact on trade due to seed mixing (seed dispersal).

293

Table 4.16.Summary of Problem Formulation performed in the context of a hypothetical
environmental risk assessment process of GE cucumber plants engineered for dehydration
stress tolerance using a transcription factor.
Protection Goeal:
Conservation of the
agricultural
environment
(agroecosystem)
CBF genes confer
Plant attribute
dehydration stress
(hazard)
tolerance.
.
Mechanism of CBF genes could negatively
impact on non-target
the plant
organisms, insects (Harm 3)
attribute to
and/or soil microorganisms
cause harm
(Harm 6) by causing
substantially increased
production of toxic
compounds normally
produced by cucumber.
Environmental Balanced agro-ecosystem
regarding organisms
value
population
Assessment
endpoint

Abundance of non-target
organisms.

Assessment
methodology

1) General plant phenotypic
characterization under
water stress and non-stress
conditions.
2) Compositional analysis
from field produced
samples.
If necessary according to
results from 1 and 2,
confirmatory studies with
non-target organisms to
confirm risk hypothesis of
lack of toxicity.

Exposure
pathway

Commercial release of GE
cucumber plants.

Risk
hypothesis

CBF genes will not
negatively impact the
abundance of non-target
organisms.
294

Protaction Goal:
Commercial situation:
Coexistance between
different production systems
Cucumber is a cross-pollinated
species.

No specific mechanism due to the
transgene. Gene flow from GE
cucumber pollen to conventional or
organic cucumber plants (Harm 13).

Absence of adventitious presence in
conventional and/or organic
cucumber crops.
Cross-pollination between GE
cucumber plants and conventional or
organic cucumber plants.

Identification of CBF genes at the
molecular level (PCR analysis) in
conventional or organic cucumber
plants.

Commercial release of GE cucumber
plants growing adjacent/nearby to
conventional or organic cucumber.
GE cucumber plants will not
determine adventitious presence of
CBF genes in conventional and/or
organic cucumber crops growing
according to risk management
measures for coexistence.

APPENDIX

295

APPENDIX
Table A4.1. Minimum temperatures (°C) from March 15th to April 30th in the south and north
regions of Uruguay in the period 2006 to 2010.
Average minimum
Region
Year temperature from
03/15 to 04/30 (°C)
South
2006
12.0
South
2007
13.8
South
2008
11.8
South
2009
10.0
South
2010
11.3
Average South
11.8
North
2006
13.3
North
2007
16.8
North
2008
12.3
North
2009
13.8
North
2010
10.4
Average North
13.3
Source of data: Agroclimatic Information
System (GRAS) of the National Agricultural
Research Institute (INIA),
http://www.inia.org.uy/gras/

296

REFERENCES

297

REFERENCES

Achard P, Gong f, Cheminant S, Alioua M, Hedden P and Genschik P. 2008. The ColdInducible CBF1 Factor–Dependent Signaling Pathway Modulates the Accumulation of
the Growth-Repressing DELLA Proteins via Its Effect on Gibberellin Metabolism. The
Plant Cell 20:2117-2129.
Aldabe DL. 2000. El cultivo de pepino. In: Producción de Hortalizas en Uruguay. Ed.
Epsilon. Montevideo. pp 188-190.
Atkinson NJ and Urwin PE. 2012. The interaction of plant biotic and abiotic stresses: from
genes to the field. J. of Exp. Bot. 63(10):3523-3543.
Bates DM and Robinson RW. 1995. Cucumbers, melons and water-melons. Cucumis and
Citrullus (Cucurbitaceae). In: Smart and Simonds. ed. Evolution of crop plants.
Longman. pp. 89-96.
__________, __________ and Jeffrey CH. 1990. Biology and utilization of the
Curcurbitaceae. Cornell University Press. Ithaca, New York.
Brussa S, Antonio C, Grela G, Andrés I. 2007. Flora arbórea del Uruguay, con énfasis en las
especies de Rivera y Tacuarembó. 544p.
Carlini CR and Grossi-de-Sá MF. 2002. Plant toxic proteins with insecticidal properties. A
review on their potentialities as bioinsecticides. Toxicon 40:1515-1539.
Chambliss OL and Jones CM. 1966. Cucurbitacins: Specific insect attractants in
Cucurbitaceae. Science 153:1392-1393.
Chan Z, Bigelow PJ, Loescher W, Grumet R. 2011. Comparison of salt stress resistance
genes in transgenic Arabidopsis thaliana indicates that extent of transcriptomic change
may not predict secondary phenotypic or fitness effects. Plant Biotechnology Journal
pp. 1–17.
Chapman MA and Burke JM. 2006. Transley Review. Letting the gene out of the bottle: the
population genetics of genetically modified crops. New Phytologist 170:429-443.
Chen J, Staub JE, Tashiro Y, Isshiki S and Miyazaki S. 1997. Successful interspecific
hybridization between Cucumis sativus L. And C. hystrix Chakr. Euphytica 96: 413419.
Chen J, Staub JE, Adelberg J, Lewis S and Kunkle B. 2002. Synthesis and preliminary
characterization of a new species (amphidiploid) in Cucumis. Euphytica 123:315-322.
CODEX ALIMENTARIUS. 2003. Guideline for the conduct of food safety assessment of
foods derived from recombinant-DNA plants. Codex Alimentarius Commission, Joint
FAO/WHO Food Standards Programme, Rome. CAC/GL 45.
http://www.fao.org/docrep/011/a1554e/a1554e00.htm
298

Collison CH. 1973. Nectar secretion and how it affects the activity of honey bees in the
pollination of hybrid pickling cucumbers, Cucumis sativus L.Thesis (M.S.). Michigan
State University. Dept. of Entomology, 1973.
Conner AJ, Glare TR and Nap J. 2003. The release of genetically modified crops into the
environment. Part II. Overview of ecological risk assessment. Plant J. 33:19-46.
Craig W, Tepfer M, Degrassi G and Ripandelli D. 2008. An overview of general features of
risk assessments of genetically modified crops. Euphytica 164:853–880.
Dadant Ch. and Dadant CP. 1976. The hive and the honey bee. Illinois, USA. 740 p.
Dale PJ, Clarke B and Fontes E. 2002. Nature Biotechnology 20(6):567-573.
Deakin JR, Bohn GW and Whitaker TW. 1971. Interspecific hybridization in Cucumis.
Economic Botany 25:195-211.
Delaney B, Astwood JD, Cunny H, Conn RE, Herouet-Guicheney C, MacIntosh,
Ellstrand NC. 2001. When transgenes wander, should we worry? Plant Physiol. 125:15431545.
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS (FAO).
2007. Instrumentos de la FAO sobre la bioseguridad (Biosecurity toolkit). Roma, Italia.
148p.
Fowler S, Thomashow MF. 2002. Arabidopsis transcriptome profiling indicates that multiple
regulatory pathways are activated during cold acclimation in addition to the CBF cold
response pathway. Plant Cell 14:1675-1690.
Gildemacher BH and JansenGJ. 1993. Cucumis sativus L. In: Siemonsma JS and Piluck K ed.
Plant resources of south east Asia No. 8 Vegetables. Pudoc Scientific Publishers.
Wageningen, Netherlands. pp. 157-160.
Gilmour SJ, Sebolt AM, Salazar MP, Everard JD, Thomashow MF. 2000. Overexpression of
the Arabidopsis CBF3 transcriptional activator mimics multiple biochemical changes
associated with cold acclimation. Plant Physiol. 124:1854-1865.
__________. Zarka DG, Stockinger EJ, Salazar MP, Houghton JM and Thomashow
MF.1998.Low temperature regulation of the Arabidopsis CBF family of AP2
transcriptional activators as an early step in cold-induced COR gene expression, Plant J.
16:433–442.
Grumet R, Wolfenbarger LR, Ferenczi A. 2011. Future possible genetically engineered crops
and traits and their potential environmental impacts. In: Grumet G, Hancock J, Maredia
K and Weebaddee C. ed. Environmental Safety of Genetically Engineered Crops. East
Lansing, USA, Michigan State University pp 47-57.
299

Hancock JF. 2003. A framework for assessing the risk of transgenic crops. Bioscience
53:512-519.
Hokanson SC, Grumet R and Hancock JF. 1997a. Effect of border rows and trap/donor ratios
on pollen-mediated gene movement. Ecological Applications 7(3):1075-1081.
Hokanson SC, Hancock JF and Grumet R. 1997b. Direct comparison of pollen-mediated
movement of native and engineered genes. Euphytica 96:397-403.
Horie H, Ito H, Ippoushi K, Azuma K, Sakata Y and Igarashi I. 2007. Cucurbitacin C – Bitter
principle in cucumber plants. JARQ 41(1):65-68.
Hsieh T, Lee JT, Yang PT, Chiu LH, Charng Yy, Wang Y, Chan MT. 2002. Heterology
expression of the Arabidopsis C-Repeat/Dehydration Response Element Binding Factor
1 gene confers elevated tolerance to chilling and oxidative stresses in transgenic
tomato. Plant Physiol. 129:1086-1094.
Hsieh TH, Lee JT, Charng Yy, Chan MT. 2002. Tomato plants ectopically expressing
Arabidopsis CBF1 show enhanced resistance to water deficit stress. Plant Physiol.
130:618-626.
Hussain SS, Kayani MA and Amjad M. 2011. Transcription factors as tools to engineer
enhanced drought stress tolerance in plants. Biotechnol. Prog. 27(2):297-306.
Jaglo KR, Kleff S, Amundsen KL, Zhang X, Haake V, Zhang JZ, Deits T, Thomashow MF.
2001. Components of the Arabidopsis C-Repeat/Dehydration-Responsive Element
Binding Factor Cold-Response pathway are conserved in Brassica napus and other
plant species. Plant Physiol. 127:910-917.
Jaglo-Ottosen KR, Gilmour SJ, Zarka DG, Schabenberger O, Thomashow MF. 1998.
Arabidopsis CBF1 overexpression induces COR genes and enhances freezing tolerance.
Science 280:104-106.
Kasuga M, Liu Q, Miura S, Yamaguchi-Shinozaki K, Shinozaki K. 1999. Improving plant
drought, salt, and freezing tolerance by gene transfer of a single stress-inducible
transcription factor. Nat. Biotechnol. 17:287-291.
Little HA, Grumet R and Hancock JF. 2009. Modified Ethylene Signaling as an Example of
Engineering for Complex Traits: Secondary Effects and Implications for Environmental
Risk Assessment. Hortscience 44(1):94–101.
Liu Q, Kasuga M, Sakuma Y, Abe H, Miura S, Yamaguchi-Shinozaki K, Shinozaki K. 1998.
Two transcription factors, DREB1 and DREB2, with an EREBP/AP2 DNA binding
domain separate two cellular signal transduction pathways in drought- and lowtemperature-responsive gene expression, respectively, in Arabidopsis. Plant Cell
10:1391-1406.
Lombardo A. 1984. Flora montevidensis. Vol.3.

300

Medina J, Bargues M, Terol J, Perez-Alonso M and Salinas J. 1999. The Arabidopsis CBF
gene family is composed of three genes encoding AP2 domain-containing proteins
whose expression is regulated by low temperature but not by abscisic acid or
dehydration. Plant Physiol. 119:463–470.
Nickson TE. 2008. Planning environmental risk assessment for genetically modified crops:
Problem Formulation for stress-tolerant crops. Plant Physiol. 147:494-502.
Pabo OC. 1992. Transcription Factors “Structural Families and Principles of DNA
Recognition”Annu. Rew Biochem. 1992. 61:1053-95
Puchalski JT and Robinson RW. 1990. Electrophoretic analysis of isozymes in Cucurbita and
Cucumis and its application for phylogenetic studies. In: Bates DM, Robinson RW and
Jeffrey C. ed. Biology and Utilization of the cucurbitaceae. Cornell University Press.
Ithaca, New York. pp. 60-76.
Purseglove JW. 1968. Tropical crops. Dicotyledons 1. England. John Wiley and Sons, Inc.
New York. pp. 107-108.
Raybould A and Quemada H. 2010. Bt crops and food security in developing countries>
realized benefits, sustainable use and lowering barriers to adoption. Food Sec. 2:247259.
Raybould A, Tuttle A, Shore S, Stone T. 2010. Environmental risk assessments for transgenic
crops producing output trait enzymes. Transgenic Res 19:595–609.
Raybould A. 2006. Problem formulation and hypothesis testing for environmental risk
assessments of genetically modified crops. Environ Biosafety Res 5:119–125.
Raybould A. 2010. Reducing uncertainty in regulatory decision-making for transgenic crops.
More ecological research or clearer environmental risk assessment? GM Crops 1(1):17. Landes Bioscience.
Riechmann JL, Heard J, Martin G, Reuber L, Jiang CZ, Keddie J, Adam L, Pineda O,
Ratcliffe OJ, Samaha RR, Crelman R, Pilgrim M, Broun P, Zhang JZ, Ghandehari D,
Sherman BK, Yu GL. Arabidopsis transcription factors:genome-wide comparative
analysis among eukaryotes. Science. 2000;290:2105–2110.
Root AI. 2005. ABC y XYZ de la apicultura, enciclopedia de la cría científica y práctica de
las abejas. 9ª. Reimp. Buenos Aires: Hemisferio Sur, 723p.
S, Meyer LS, Privalle L, Gao Y, Mattsson J and Levine M.2008. Evaluation of protein safety
in the context of agricultural biotechnology. ILSI International Food Biotechnology
Committee. Chemical Toxicology 46(supplement 2):S71-S97.
Sanvido O, Stark M, Romeis J and Bigler F. 2006. Ecological impacts of genetically
modified crops. Experiences from ten years of experimental field research and
commercial cultivation. Swiss Confedeartion, Agroscope Reckenholz-Tanikon
Researth Station (ART). ART-Schriftenreihe 1.
301

Snow AA, Andow DA, Gepts P, Hallerman M, Power A., Tiedje JM and Wolfenbarger LL.
2005. Genetically engineered organisms and the environment. Current status and
recommendations. Ecological Applications 15(2):377-404.
Stockinger EJ, Gilmour SJ and Thomashow MF. Arabidopsis thaliana CBF1
encodes an AP2 domain-containing transcriptional activator that binds to the
C-repeat/DRE, a cis-acting DNA regulatory element that stimulates ranscription
in response to low temperature and water deficit, Proc. Natl. Acad. Sci. USA 94 (1997)
1035–1040.
Tindall HD. 1983. Vegetables in the tropics. Malaysia. Macmillan. pp.159-160.
URUGUAY, MGAP DIEA DIGEGRA 2010. Horticultural surveys. South and north coast of
Uruguay. Survey Series No. 290. Direction of Agricultural Statistics (DIEA) and
General Direction of the Farm.
URUGUAY. 2010. Risk Management Commision (CGR). Minutes of meetings, 2010
URUGUAY. 2012-2013. MRREE. Statements from the Mission of Uruguay to the European
Union. Brief report on status of honey commerce regarding the judgment of the
European Court of Justice (ECJ), Case C-442/09.
URUGUAY. 2012a. Dirección Nacional de Meteorología, Dirección de climatología y
documentación. La Primavera, aspectos generales del clima durante la primavera en el
Uruguay. 4p. http://meteorologia.gub.uy/index.php/caracteristicas-estacionales-delclima
__________. 2012b. Dirección Nacional de Meteorología, Dirección de climatología y
documentación. El verano, aspectos generales del clima durante el verano en el
Uruguay. 4p. http://meteorologia.gub.uy/index.php/caracteristicas-estacionales-delclima
URUGUAY. MVOTMA. 2007. Proposal for the development of a National Biosafety
Framework. DINAMA-PNUMA- PNUMA-FMAM. URU-04-009. 148p.
URUGUAY.MGAP-DIEA-DIGEGRA. 2010. Encuestas Hortícolas 2009. Zonas Sur y
Litoral Norte. Serie Encuestas No. 290. 30p.
__________. 2010. Censo Agropecuario. Available online at
http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,5,81,O,S,0,,
__________. 2011. Censo Agropecuario. Available online at
http://www.mgap.gub.uy/portal/hgxpp001.aspx?7,5,149,O,S,0,MNU;;MNU;,

US EPA. 1998. Guidelines for Ecological Risk Assessment. Federal Register 63(93):2684626924. 188p.

302

Wolt JD, Keese P, Raybould A, Fitzpatrick JW, Burachik M, Gray A, Olin SS, Schiemann J,
Sears M and Wu F.2010. Problem formulation in the environmental risk assessment for
genetically modified plants. Transgenic Res 19:425–436.
Zamalvide JP. 2000. Calidad de aguas para riego en producciones hortícolas y frutícolas. 20p.
Zehnder G, Kloepper j, Tuzun S, Yao CH, Wei G, Chambliss O and Shelby R. 1997. Insect
feeding on cucumber mediated by rhizobacteria-induced plant resistance. Entomologia
Experimentalis et Applicata 83:81-85.
Zuloaga FO and Morrone O. 1999. Catálogo de las plantas vasculares de la República
Argentina. Zuloaga, Fernando O.,editor; Morrone, Osvaldo, eds. Botanical Garden
Missouri. V. 74. 621p.

303