The
comments have been produced by risk assessment specialists from Brazil. Please
contact Prof. Dr. Paulo P. Andrade (Andrade@ufpe.br) for further
information
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for reading:
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The
comments below (highlighted yellow over the original text and written in red on
the remark boxes) are based on the 2 April 201 revised version
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Notes
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Except
for the note, the text appears as in the CBD site
TABLE OF CONTENTS
Preface ……………………………………………………………………………………………… xx
Objective and scope of
this guidance ……………… …… xx
Part
I: Roadmap for risk assessment of living modified organisms xx
Background …………………………………………………………………………………… xx
Introduction …………………………………………………………………………………… xx
Overarching issues
in the risk assessment process ……………………… xx
Quality and
relevance of information ………………………………………………… xx
Identification and consideration of uncertainty … xx
Planning
phase of the risk assessment ………………………………………………………… xx
Establishing
the context and scope …………………………………………………… xx
The choice of
comparators ……………………………………………………………… xx
Conducting the risk
assessment ……………………………………………………………… xx
Step 1: “an identification of any novel genotypic and
phenotypic characteristics
associated with the living modified organism that may have adverse effects on
biological diversity in the likely potential receiving environment, taking also
into
account risks to human health” ………………………………………………………… xx
Step 2: “an evaluation of the likelihood of adverse
effects being realized, taking into
account the level and kind of exposure of the likely potential receiving
environment
to the living modified organism” ……………………………………………………… xx
Step 3:
“an evaluation of the consequences should these adverse effects be realized” … xx
Step 4: “an estimation of the overall risk posed by the
living modified organism based
on the evaluation of the likelihood and consequences of the identified adverse
effects
being realized” ………………………………………………………………………… xx
Step 5: “a recommendation as to whether or not the risks
are acceptable or manageable, including, where necessary, identification of
strategies to manage these risks” ……… xx
Annex: Flowchart for the risk
assessment process …………………………………………… xx
Part II: Specific types of
LMOs and traits ………………………………………………………… xx
Risk
assessment of living modified plants with stacked genes or traits …………………… xx
Introduction ……………………………………………………………………………… xx
Objective and scope……………………………………………………………………… xx
Planning phase of the risk assessment …… xx
The choice of comparators …………………… xx
Conducting
the risk assessment …………………………… xx
Sequence characteristics at the insertion sites, genotypic
stability and genomic organization ……………………………………………………………………… xx
Potential interactions between combined genes and their
resulting phenotypic
changes and effects on the environment …………… xx
Combinatorial and cumulative effects ………………………………… xx
Crossing and segregation of transgenes …………………… xx
Methods for
distinguishing the combined transgenes in a stacked event from the parental
LMOs …………………………………………………………………… xx
Risk
assessment of living modified plants with tolerance to abiotic stress ……………… xx
Background …………………………………………………………………………… xx
Introduction …………………………………………………………………………… xx
Planning
phase of the risk assessment ………………………………………………… xx
The choice of comparators ……………………………………………………… xx
Conducting the risk assessment ……………………………………………………… xx
Unintended characteristics, including crosstalk between
stress responses ……………… xx
Testing the LM plant in representative environments ………………… xx
Increased persistence in agricultural areas and invasiveness
of natural habitats … xx
Effects on the abiotic environment and ecosystem ………………………… xx
Risk assessment of living modified mosquitoes …………………………………………… xx
Introduction …………………………………………………………………………… xx
Objective and scope …………………………………………………………………… xx
Planning phase of the risk assessment ………………………… xx
The
choice of comparators ……………………………………………………… xx
Conducting
the risk assessment ……………………………………………………… xx
Characterization
of the LM mosquito …………………………………………… xx
Effects on biological diversity (species, habitats,
ecosystems, and ecosystem
function and services) …………………………………………………………… xx
Vertical
gene transfer ………………………………………………… xx
Horizontal gene transfer ………………………………………………………… xx
Persistence
of the transgene in the ecosystem ……………………… xx
Evolutionary
responses (especially in target mosquito vectors or pathogens of
humans and animals) ……………………………………………………………… xx
Unintentional
transboundary movement …………………… xx
Risk management strategies ……………………………………………………… xx
PREFACE
In accordance with the precautionary approach the
objective of the Protocol is “to contribute to ensuring an adequate level of
protection in the field of the safe transfer, handling and use of living
modified organisms resulting from modern biotechnology that may have adverse
effects on the conservation and sustainable use of biological diversity, taking
also into account risks to human health, specifically focusing on transboundary
movements”. For this purpose, Parties shall ensure that risk assessments
are carried out to assist in the process of making informed decisions regarding
living modified organisms (LMOs).
According to Article 15 of the Protocol, risk
assessments shall be carried out in a scientifically sound manner and be based,
at a minimum, on information provided in accordance with Article 8 and other
available scientific evidence in order to identify and evaluate the possible
adverse effects of LMOs on the conservation and sustainable use of biological
diversity, taking also into account risks to human health.
Four general principles of risk assessment are specified
in Annex III of the Protocol:
·
“Risk assessment should be carried out in a
scientifically sound and transparent manner, and can take into account expert
advice of, and guidelines developed by, relevant international organizations”.
·
“Lack of
scientific knowledge or scientific consensus should not necessarily be
interpreted as indicating a particular level of risk, an absence of risk, or an
acceptable risk”.
·
“Risks associated with living modified organisms or
products thereof should be considered in the context of the risks posed by the
non-modified recipients or parental organisms in the likely potential receiving
environment”.
·
“Risk assessment should be carried out on a
case-by-case basis. The required information may vary in nature and level of
detail from case to case, depending on the LMO concerned, its intended use and
the likely potential receiving environment”.
This document was developed by the Ad Hoc Technical
Expert Group (AHTEG) on Risk Assessment and Risk Management, with input from
the Open-ended Online Expert Forum, in accordance with terms of reference set
out by the Conference of the Parties serving as the meeting of the Parties to
the Cartagena Protocol on Biosafety (COP-MOP) in its decisions BS-IV/11 and
BS-V/12 in response to an identified need for further guidance on risk
assessment of LMOs. It is intended to be a “living document” that will be
updated and improved as appropriate and when mandated by the Parties to the
Cartagena Protocol on Biosafety.
OBJECTIVE AND SCOPE
OF THIS GUIDANCE
The objective of this Guidance is “to provide a
reference that may assist Parties and other Governments in implementing the
provisions of the Protocol with regards to risk assessment, in particular its
Annex III and, as such, this Guidance is not prescriptive and does not impose
any obligations upon the Parties”.
This Guidance consists of two parts. In Part I, the
Roadmap for Risk Assessment of LMOs is presented. In Part II, specific guidance
is provided on the risk assessment of specific types of LMOs and traits. The
topics contained in Part II were identified and prioritized by the Open-ended
Online Expert Forum and the AHTEG in accordance with the terms of reference in
decisions BS-IV/11 and BS-V/12, taking into account the need of Parties for
additional guidance.
PART I
Roadmap for RISK ASSESSMENT OF Living Modified Organisms
BACKGROUND
This “Roadmap” provides guidance
on assessing environmental risks of living modified organisms (LMOs), taking
into account risks to human health, consistent with the Cartagena Protocol on
Biosafety (hereinafter “the Protocol”) and in particular with its Article 15
and Annex III. Accordingly, this Roadmap complements Annex III and national
biosafety policies and legislations. Specifically, the Roadmap facilitates and
enhances the effective use of Annex III by elaborating on the steps and points
to consider in environmental risk assessment and by directing users to relevant
background materials. The Roadmap may be useful as a reference for risk
assessors when conducting or reviewing risk assessments and as a training tool
in capacity-building activities.
This
Roadmap provides information that is broadly relevant
to the risk assessment of all types of LMOs and
their intended uses within the scope and objective of the Protocol. However, it
has been developed based largely on living modified (LM) crop plants because
the experience to date with environmental risk assessments of LMOs has been
mainly gained from these organisms.
The Roadmap may be applied to all types of environmental releases of
LMOs, including those of limited duration and scale as well as large-scale
releases. Nevertheless, the amount and type of information available and needed
to support risk assessments of the different types of intentional release into
the environment may vary from case to case.
INTRODUCTION
According to the Protocol, risk assessment of LMOs is
a structured process conducted in a scientifically sound and transparent
manner, and on a case-by-case
basis in relation to the likely potential receiving environment. Its purpose is
to identify and evaluate the potential adverse effects of LMOs, and their likelihood and consequences as well as to make a
recommendation as to whether or not the risks are acceptable or manageable. Risk assessments serve as an input for
decision-making regarding LMOs. This Roadmap describes an integrated risk
assessment process in three sub-sections: “Overarching Issues in the Risk
Assessment Process”, “Planning Phase of the Risk Assessment”, and “Conducting
the Risk Assessment”.
The potential
effects caused by an LMO may vary depending on the characteristics of the LMO, on
how the LMO is used, and on the environment exposed to the LMO. The effects may
be intended or unintended, and may be
considered beneficial, neutral or adverse depending on the impact on a protection goal.
What is
considered an adverse effect as well as an “acceptable risk”
depends on protection goals and
assessment endpoints.
The choice of protection goals may be informed by the Party`s national policies
and legislation as well Annex 1 of the Convention on Biological Diversity
as relevant to the Party responsible for conducting the risk assessment.
The Roadmap includes five steps drawn from Annex III that describe a tiered
process in which the results of one step are relevant to other steps. Importantly,
the steps of a risk assessment may need to be conducted in an iterative manner,
where certain steps may be repeated or re-examined when new information arises
or a change in circumstances has occurred that could change its conclusions.
Similarly, issues included in the ‘Establishing the
context and scope’ section below may be taken into consideration while
conducting the risk assessment and again at the end of the risk assessment
process to determine whether the objectives and criteria set out at the
beginning of the risk assessment have been addressed.
Ultimately, the concluding recommendations derived
from the risk assessment are taken into account in the decision-making process for
an LMO. In the decision-making process, in accordance with the country’s
policies and protection goals, other Articles of the Protocol or other relevant
issues may also be taken into account and are listed in the last paragraph of
this Roadmap: ‘Related Issues’.
The risk assessment process according to the Roadmap
is illustrated in Figure 1.
›› See references relevant to “Introduction”:
Overarching
issues in the risk assessment process
This section gives guidance on issues that are
relevant to all the steps of the risk assessment. It focuses on provisions
related to the quality and relevance of information to be considered in the
risk assessment, as well as the means to identify and describe uncertainties
that may arise.
Quality and
relevance of information
An important question in a risk assessment is whether
the information presented is of sufficient quality and relevance to
characterize the risk posed by the LMO.
A number of issues should be considered to ensure the
quality and relevance of the information used as well as the outcome of the
risk assessment. For example:
- Criteria for the quality of scientific
information.
- Data of acceptable scientific quality should
be used in the risk assessment. Data quality should be consistent with
the accepted practices of scientific evidence-gathering and reporting and
may include independent review of the methods and designs of studies.
- Appropriate
statistical methods should be used to strengthen the scientific
conclusions of a risk assessment and, where appropriate, be described in
the risk assessment report. Risk assessments frequently use data generated from multiple
scientific fields, which may be divergent or even contradictory;
- Reporting of data and methods should be
sufficiently detailed and transparent to allow independent verification
and reproduction. This would include ensuring the accessibility of data used
by the risk assessors (e.g., the availability of relevant data or
information and, if requested and as appropriate, sample material),
taking into account the provisions of Article 21 of the Protocol on the
confidentiality of information;
- The relevance of
information for the risk assessment
- Data may be considered relevant if they are
linked to protection goals or assessment endpoints, contribute to the
identification and evaluation of the potential adverse effects of the
LMO, or if they can affect the outcome of the risk assessment or the
decision.
- Relevant data may be derived from a variety of
sources such as new experimental data, data from relevant peer reviewed
scientific literature, as well as data and experience from previous risk
assessments, regarded as of acceptable scientific quality, in particular
for the same or similar LMOs introduced in similar receiving
environments.
- Information from national and
international standards and guidelines may be used in the risk assessment,
as well as knowledge and experience of farmers, growers, scientists,
regulatory officials, and indigenous and local communities depending on
the type of LMO;
- The process of risk assessment may give
rise to the need for further relevant information about specific subjects,
which may be identified and requested during the assessment process,
while on the other hand information on other subjects may not be relevant
in some instances.
- The information that is relevant to
perform a risk assessment will vary from case to case depending on the
nature of the modification of the LMO, on its intended use, and on the
scale and duration of the environmental introduction. In cases of
environmental releases whose objective is to generate information for
further risk assessments and where exposure of the environment to the
LMO is limited, such as for some early-stage experimental releases and
trials, less information may be available or required when performing the
risk assessment. The uncertainty resulting from the limited information
available in such cases may be addressed by risk management and
monitoring measures.
- To
the extent possible, impartial experts with relevant background in the
different scientific disciplines should be involved in conducting or
providing inputs to risk assessments. Experts
should not be biased or improperly impaired by interests that could be
affected by the assessment in which they participate.
Identification and consideration of uncertainty
Uncertainty is an inherent and integral element of
scientific analysis and risk assessment. According to the Protocol,
“where there is uncertainty regarding the level of risk, it may be addressed by
requesting further information on the specific issues of concern or by
implementing appropriate risk management strategies or monitoring the living modified organism
in the receiving environment”. The Protocol also states that “lack of scientific
certainty due to insufficient relevant scientific information and knowledge
regarding the extent of the potential adverse effects of a living modified
organism on the conservation and sustainable use of biological diversity in the
Party of import, taking also into account risks to human health, shall not
prevent that Party from taking a decision, as appropriate, with regard to the
import of the living modified organism in question (…), in order to avoid or
minimize such potential adverse effects”. Whether and to what extent there is scientific uncertainty is therefore
critical in the context of precautionary action. There is no internationally agreed
definition of “scientific uncertainty”, nor are there internationally agreed
general rules or guidelines to determine its occurrence. The issue of
uncertainty is dealt with – sometimes differently – in each international
instrument incorporating precautionary measures.
Considerations of uncertainty strengthen the scientific
validity of a risk assessment. An analysis of uncertainty includes
considerations of its source and nature, and focuses on uncertainties that can
have a significant impact on the conclusions of the risk assessment.
For
each identified uncertainty, the nature
of the uncertainty may be described as arising from: (i) lack of information,
(ii) incomplete knowledge, and (iii) biological or experimental variability,
for example, due to inherent heterogeneity in the population being studied or
to variations in the analytical assays. Uncertainty
resulting from lack of information includes, for example, information
that is missing and data that is imprecise or inaccurate (e.g., due to study
designs, model systems and analytical methods used to generate, evaluate and
analyze the information).
In some cases more information will not necessarily
contribute to a better understanding of potential adverse effects, therefore risk
assessors should look to ensure that any further information requested will
contribute to better evaluations of the risk(s). Although uncertainties
originating from lack of information may be reduced by further research,
uncertainties arising from incomplete knowledge or from inherent variability
may be irreducible. In such cases, instead of reducing uncertainty, the
provision of additional information may actually give rise to new
uncertainties.
As such, the various forms of uncertainty should be
considered and described in each step of the risk assessment. In addition, when communicating the results of a risk
assessment, it is important to describe, quantitatively or
qualitatively, what impact uncertainty may have on the estimated level of risk
and on the conclusions and recommendations of the risk assessment.
In cases where the nature of the uncertainty
implies that it cannot be addressed through the provision of more data during
the risk assessment, where necessary, it may be dealt with by risk management and/or monitoring in accordance with
paragraphs 8(e) and 8(f) of Annex III (see step
5).
›› See references relevant to
“Identification and consideration of uncertainty”:
PLANNING PHASE OF
THE RISK ASSESSMENT
Establishing the context and scope
Risk assessments are
carried out on a case-by-case basis, in relation to the likely potential
receiving environment. Each risk assessment starts by establishing its context
and scope in a way that is consistent with the country’s protection goals,
assessment endpoints, risk thresholds, management strategies
and policies.
Establishing the
context and scope for a risk assessment in line with the country’s policies and
regulations may involve an information-sharing and consultation process with risk
assessors, decision-makers and various stakeholders prior to conducting the
actual risk assessment, to identify protection goals, assessment endpoints and
risk thresholds relevant to the assessment. It may also involve identifying
questions to be asked that are relevant to the case being considered. The risk assessors should,
at the outset of the process, have knowledge of national requirements for risk
assessment and criteria for acceptability of risks. They may also use questions or
checklists designed for the case under consideration to assist in the
subsequent steps.
Several points may be taken into consideration, as
appropriate, that are specific to the Party involved and to the particular risk
assessment. These include:
·
Existing environmental and health policies and
strategies based on, for instance:
(i)
Regulations and international obligations of the Party
involved;
(ii)
Guidelines or regulatory frameworks that the Party has
adopted; and
(iii)
Protection goals, assessment endpoints, risk
thresholds and management strategies as laid down, for instance, in relevant
legislation of the Party;
·
Intended handling and use of the LMO, including
practices related to the use of the LMO, taking into account user practices and
habits;
·
The nature and level of detail of the information that
is needed (see above), which may, among other things, depend
on the biology/ecology of the recipient organism, the intended use of the LMO
and its likely potential receiving environment, and the
scale and duration of the environmental exposure (e.g., whether it is for
import only, field testing or for commercial use). For small-scale releases,
especially at early experimental stages, the nature and detail of the
information that is required or available may differ compared to the
information required or available for large scale or commercial environmental
release.
·
Identification of methodological and analytical
requirements, including requirements for review mechanisms, that must be met to
achieve the objective of the risk assessment as specified, for instance, in
guidelines published or adopted by the Party that is responsible for conducting
the risk assessment (i.e. typically the Party of import according to the
Protocol);
·
Experience and history of use of the
non-modified recipient organism, taking into account its ecological function.
·
Approaches for describing the potential adverse
effects of the LMO and its transfer, handling and use,
·
Use of terms for describing the likelihood (step 2),
the magnitude of consequences (step 3) and risks (step 4), and the
acceptability or manageability of risks (step 5).
Some risk assessment frameworks combine the process of
setting the context and scope of the risk assessment with the identification of
potential adverse effects associated with the modifications of the LMO into a
single step called “Problem formulation” (see step 1).
›› See references relevant to
“Setting the context and scope”:
The choice of comparators
Risk
assessments can be conducted
in a comparative manner where risks associated with an LMO are considered in
the context of the risks posed by the non-modified recipients or parental
organisms in the likely potential receiving environment.
The
comparative approach aims at identifying changes between an LMO and its
comparator(s) that may lead to adverse effects. The choice of comparators can
have large effects on the relevance, interpretation and conclusions drawn from
the risk assessment process. Therefore, the one or more comparators that are chosen
should be selected on the basis of their capacity to generate information that
is consistent and relevant for the risk assessment.
To
account for variation due to interaction with the environment, the LMO and its comparator(s) should ideally be evaluated at the same
time and location, and under the same environmental conditions.
In
other risk assessment frameworks, the choice of an appropriate comparator will
depend on the specific LMO being considered, the step in the risk assessment
and on the questions that are being asked.
In some
cases, the non-modified recipient organisms or the parental organisms alone may
not be sufficient to establish an adequate basis for a comparative risk
assessment, such as for the risk assessment of certain LM plants tolerant to
abiotic stress, stacked LMOs, LM mosquitoes, and pharmaceutical producing LMOs.
In such cases additional comparators may be necessary (for more guidance on
some of these examples, please refer to Part II of this Guidance).
CONDUCTING The risk
assessment
To fulfil its objective under Annex III, as well as
other relevant Articles of the Protocol, risk assessment as described in Annex
III is conducted in steps in an integrated process and iterative manner, as
appropriate. Paragraph 8 of Annex III describes the key steps of the risk
assessment process. Paragraph 9 of Annex III lists and describes points to
consider in the process for risk assessment of LMOs depending on the particular
case.
The steps of risk assessment under the Protocol are
similar to those used in other risk assessment frameworks. Although the
terminology may differ between the various
approaches, in general terms, risk
assessment is defined as a science-based process that includes at least the
following common components (corresponding to the steps 1 to 4
respectively): “hazard identification”, “exposure assessment”, “hazard characterization”,
and “risk characterization”.
In this section, the steps indicated in paragraph 8(a)-(e)
of Annex III are described in further detail and points to consider are
provided for each step. Some points to consider are taken from paragraph 9 of
Annex III. Additional points to consider were added on the basis of commonly
used methodologies of LMO risk assessment and risk management insofar as they
were in line with the principles of Annex III. The relevance of each point to
consider will depend on the case being assessed. The guidance provided below on
the steps in risk assessment is not exhaustive, thus additional guidance and
points to consider may be relevant, as appropriate. Lists of background
documents relevant to each section are provided through the links.
›› See references
relevant to “Conducting the Risk Assessment”:
Step 1: “An identification of any
novel genotypic and phenotypic characteristics associated with the living
modified organism that may have adverse effects on biological diversity in the
likely potential receiving environment, taking also into account risks to human
health.”
Rationale:
The purpose of this step is to identify changes
in the LMO that could cause adverse effects on the conservation and sustainable
use of biological diversity, taking also into account risks to human health. The potential
adverse effects may be direct or indirect, immediate or delayed.
The
question that risk assessors ask in this step is what adverse effects could
occur, why and how. This step is very important in the risk assessment process
as the questions raised will determine what risk scenarios are considered in
all subsequent steps. This step may also be referred to as “hazard identification”
– the difference between the concepts of “hazard” and “risk”
is important and must be understood by the risk assessor. In many cases,
this step is performed as part of a problem formulation process when setting the
context and scope of the risk assessment. In that case, this step is not
limited to the identification of hazards, but also takes into account
protection goals and appropriate assessment endpoints.
In this step, risk
assessors identify scientifically plausible scenarios and risk hypotheses to
predict if the LMO could have an adverse effect on the assessment endpoints. In
doing so, risk assessors analyse what novel characteristics of the LMO, as well
as its transfer, handling and use, could give rise to adverse effects in an
interaction with the likely potential receiving environment. For example, if the protection goal is maintenance of
biodiversity, a risk hypothesis could assess what novel characteristics of the
LMO might affect specific “targets” such as a component of the
food web or the population size of certain species in the likely potential
receiving environment. The targets are called assessment endpoints, and their
unambiguous specification is crucial to focus the risk assessment.
It is important to
define a causal link or pathway between a characteristic of the LMO and a
possible adverse effect, otherwise the risk assessment may generate information
that will not be useful for decision-making (see also steps 2 and 3). Depending
on the LMO, its intended use and the likely potential receiving environment,
possible concerns that could lead to adverse effects include, but are not
limited to, the potential of the LMO to: (i) affect non-target organisms, (ii)
cause unintended effects on target organisms, (iii) become persistent or invasive
or develop a fitness advantage in ecosystems with limited or no management,
(iv) transfer genes to other organisms/populations, and (v) become
genotypically or phenotypically instable.
In this
step, a comparison of the LMO may be carried out with the non-modified
recipient or parental organisms in the likely potential receiving environment,
taking into consideration the new trait(s) of the LMO (see ‘The choice of
comparators’ in the chapter on ‘Planning Phase’).
The novel
characteristics of the LMO to be considered can be described
in genotypic and phenotypic terms. These include any
changes in the LMO, ranging from the nucleic acid (including any deletions), to gene expression level to
morphological changes. The novel
characteristics of the LMO may cause adverse effects which may be intended or
unintended, direct or indirect, immediate or delayed, combinatorial or cumulative, as well as predicted or
unpredicted. For example, an adverse effect may also be caused by changes in the expression levels
of endogenous genes as a result of the genetic modification or by combinatorial
effects of two or more genes, gene products or
physiological pathways.
Points to consider regarding characterization of the LMO:
(a)
Relevant characteristics of the non-modified recipient
organism, such as:
(i)
its biological characteristics, in particular those
that, if changed or upon interaction with the new gene products or traits of the LMO, could
lead to changes that may cause adverse effects;
(ii)
its taxonomic relationships;
(iii)
its origin, centres of origin and centres of genetic
diversity;
(iv)
ecological function; and
(v)
whether it is a component of biological diversity that
is important for the conservation and sustainable use of biological diversity
in the context of Article 7(a) and Annex I of the Convention;
(b)
Characteristics related to the transformation
method, including the characteristics of the vector such as its identity, source or origin
and host range, and information on whether the transformation method
results in the presence of (parts of) the vector in the LMO, including any
marker genes;
(c)
Relevant characteristics of the genes and of other
functional sequences, such as promoters, that have been inserted into the LMO
(e.g., functions of the gene and its gene product in the donor organism with
particular attention to characteristics in the recipient organism that could
cause adverse effects);
(d)
Molecular characteristics of the LMO related to the
modification, such as characteristics of the modified genetic elements;
insertion site(s) and copy number of the inserts; stability, integrity and
genomic organization in the recipient organism; specificity of the genetic
elements (e.g., transcription factors); levels of gene expression and intended
and unintended gene products;
(e)
Genotypic (see point (d) above) and phenotypic changes
in the LMO, either intended or unintended, in comparison with the non-modified
recipient, considering those changes that could cause adverse effects. These may include changes in
native/endogenous gene expression and regulation at the transcriptional,
translational and post-translational levels due to the insert itself or to
genomic changes that have occurred due to transformation or recombination.
Points to
consider regarding the intended use and the likely potential receiving
environment:
(f)
Protection goals and assessment endpoints relevant to
the likely potential receiving environment (see Planning phase, Setting the
context and scope);
(g)
Availability of sufficient data to establish a
meaningful baseline for the likely receiving
environment which will serve as a basis for the risk assessment;
(h)
The intended spatial scale, duration and level of
confinement (such as biological confinement) of the environmental release,
taking into account user practices and habits;
(i)
Characteristics of the likely potential receiving
environment including relevant ecosystem functions and services, in particular
its attributes that are relevant to potential interactions of the LMO that
could lead to adverse effects (see also paragraph (k) below), taking into
account the characteristics of the components of biological diversity,
particularly in centres of origin and centres of genetic diversity;
Points to
consider regarding the potential adverse effects resulting from the interaction
between the LMO and the likely potential receiving environment:
(j)
Characteristics of the LMO in relation to the likely
potential receiving environment (e.g., information on phenotypic traits that
are relevant for its survival, or its potential adverse effects – see also paragraph (e) above);
(k)
Considerations for unmanaged and managed ecosystems
concerning the use of an LMO that are relevant for the likely potential receiving
environment. These include potential adverse effects resulting from the use of
an LMO, such as changes in
farm management practices; dispersal of the LMO through mechanisms such
as seed dispersal or outcrossing within or between species, or through transfer into
habitats where the LMO may persist or proliferate; as well as effects on
species distribution, food webs and changes in bio-geochemical characteristics;
(l)
Potential for outcrossing and transfer of transgenes, via vertical gene transfer,
from an LMO to other sexually compatible species that could lead to introgression
of the transgene(s) into populations of sexually compatible species, and
whether these would lead to adverse effects;
(m)
Whether
horizontal gene transfer
of transgenic sequences from the LMO to other organisms in the likely potential
receiving environment could occur and whether this would result in potential
adverse effects. With regard to horizontal gene transfer to micro-organisms
(including viruses), particular attention may be given to cases where the LMO
is also a micro-organism;
(n)
Potential adverse effects on target organisms
such as pests and weeds developing
resistance to the target trait (e.g., pesticides and herbicides);
(o)
Potential adverse effects on non-target
organisms such as toxicity, allergenicity and multi-trophic effects which can
affect the survival, development, or behaviour of these organisms;
(p)
Potential adverse effects of the
incidental exposure of humans to (parts of) the LMO (e.g., exposure to modified
gene products in pollen), and the toxic or allergenic effects that may ensue
taking into account the agricultural practices that may be used with the LMO,
such as type of irrigation, number and amount of herbicide applications,
methods for harvesting and waste disposal, etc;
›› See references relevant to “Step 1”:
Step 2: “An
evaluation of the likelihood of adverse effects being realized, taking into
account the level and kind of exposure of the likely potential receiving
environment to the living modified organism.”
Rationale:
In order to determine and characterize the overall
risk of an LMO (step 4), risk assessors evaluate the likelihood that each of
the potential adverse effects identified in step 1 will occur. The evaluation
of likelihood may be undertaken at the same time as the evaluation of the
consequences should the adverse effects be realized (step 3) or in an inverse
order.
This step may be referred to as “exposure assessment”
where plausible pathways of a hazard leading to adverse effects are identified.
It aims to determine whether the receiving environment will be exposed to an
LMO that has the potential to cause adverse effects, taking into consideration
the intended transfer, handling and use of the LMO, and the expression level,
dose and environmental fate of transgene products
For each of the risk hypotheses or scenarios
identified in step 1, the route of exposure to the LMO being assessed (or its
products) should be determined. Furthermore, when possible the causal link
between the LMO and the potential adverse effect should be established. This
can be achieved by building conceptual models describing relationships between
the LMO, pathways of exposure and potential adverse effects in the environment.
For example, for an LMO producing a potentially toxic gene product, oral,
respiratory or dermal exposure pathways could be relevant.
Experimental studies and models may be used for an
assessment of the potential level and type of exposure, combined with the use
of statistical tools relevant for each case. Past
experience with similar situations (e.g., same recipient organism, LMO, trait,
receiving environment, etc), if available, may also be used in assessing the
level and type of exposure, taking into account user practices and habits.
In some circumstances, particularly when there is a high level of uncertainty,
it may be difficult to assess the likelihood of adverse effects being realized.
In such cases, the “worst-case scenario” may be considered by assigning a likelihood of 100% that an
adverse effect will occur and concentrating on the evaluation of its
consequences.
Likelihood may be expressed quantitatively or
qualitatively. For example, qualitative terms
could include ‘highly likely’, ‘likely’, ‘unlikely’, and ‘highly unlikely’.
Parties may consider describing these terms and their uses in risk assessment
guidelines published or adopted by them.
Points to consider:
(a)
The relevant characteristics of the likely potential
receiving environment that may be a factor in the occurrence of the potential
adverse effects (see also step 1 (f), (g) and (i)), taking into account the
variability of the environmental conditions and long-term adverse effects related to the exposure
to the LMO.
(b)
Levels of expression in the LMO and persistence and
accumulation in the environment (e.g., in the food chain) of substances with
potentially adverse effects newly produced by the LMO, such as toxins,
allergens and some insecticidal proteins. In the case of field trials, the level of persistence
and accumulation in the receiving environment may be low depending on the scale of the release,
its temporary nature and the implementation of management measures;
(c)
Information on the location of the release and the
receiving environment (such as geographic and biogeographic information,
including, as appropriate, geographic coordinates);
(d)
Factors that may affect spread of the LMO, such as its
ecological range and ability to move (e.g., LM insects, birds and fish may be
particularly mobile);
its reproductive ability (e.g., numbers of offspring, time to seeding,
abundance of seed and vegetative propagules, dormancy, pollen viability); and its
ability to spread using natural means (e.g., wind, water) or anthropogenic mechanisms
(e.g., rearing or cultivation practices, seed saving and exchange, etc);
(e)
Factors that affect presence or persistence of the LMO
that may lead to its establishment in the environment, such as, in the case of
LM plants, lifespan, seed dormancy, ability of LM seedlings to establish among
existing wild or cultivated vegetation and to reach reproductive stage, or the
ability to propagate vegetatively;
(f)
When assessing the likelihood of outcrossing from the
LMO to sexually compatible species, the following issues are relevant:
(i)
the biology of the sexually compatible species;
(ii)
the potential environment where the sexually
compatible species may be located;
(iii)
Introgression of the transgene
into the sexually compatible species;
(iv)
Persistence of the transgene
in the ecosystem; and
(g)
Expected type and level of exposure of the environment
where the LMO is released, and mechanisms by which incidental exposure could
occur at that location or elsewhere (e.g., gene flow, incidental exposure due to losses
during transport and handling, intentional spread by people, or unintentional
spread by people via machinery, mixed produce or other means).
›› See references relevant to “Step 2”:
Step 3: “An evaluation of the
consequences should these adverse effects be realized.”
Rationale:
This step, which may also be referred to as “hazard
characterization”, describes an evaluation of the magnitude of the consequences
of the possible adverse effects, based on the risk scenarios established in
step 1, paying special attention to protected areas and centres of origin and
centres of genetic diversity, and taking into account protection goals and
endpoints of the country where the risk assessment is
being carried out. As discussed in the previous step, the evaluation of
consequences of adverse effects may be undertaken at the same time as the
evaluation of likelihood (step 2) or in an inverse order.
In this step, results of tests conducted under
different conditions, such as laboratory experiments or experimental releases,
may be considered. The scale and duration of the intended use (e.g., small or
large) may influence the severity of potential consequences and should
therefore be taken into account.
The evaluation of consequences of adverse
effects can be comparative and considered in the context of the adverse effects
caused by the non-modified recipients or parental organisms in the likely
potential receiving environment, (see Planning Phase of the Risk Assessment). The
evaluation of consequences may also consider the adverse effects associated
with the existing practices or with practices that will be introduced along
with the LMO (such as various agronomic practices, for example, for pest or
weed management).
It is important to also assess in this step the
duration of the potential adverse effect (i.e., short or long term), the scale
(i.e., are implications local, national or regional), the mechanisms of effect
(direct or indirect), the reversibility (or lack thereof) of effects, and the
expected ecological scale (i.e., individual organisms – for example of a
protected species – or populations).
The evaluation of the consequence of adverse effects
may be expressed qualitatively or quantitatively. For instance, qualitative terms
such as ‘major’, ‘intermediate’, ‘minor’ or ‘marginal’ may be used. Parties may
consider describing these terms and their uses in risk assessment guidelines
published or adopted by them.
Points to consider:
(a)
Relevant knowledge and experience with the
non-modified recipient or parental organisms, or current agricultural practices
with the organism that the LMO would replace, in the likely potential receiving
environment. This may include the effects of:
(i) agricultural practices on the level of inter- and intra-species gene flow;
dissemination of the recipient; abundance of volunteers in crop rotation; change in
abundance of pests, beneficial and other organisms such as pollinators, decomposers,
organisms involved in biological control or soil microorganisms involved in
nutrient cycling;
(ii) pest management affecting non-target
organisms through pesticide
applications or other management approaches while following accepted agronomic
practices;
(iii) the
behaviour of populations of unmodified animal or insect species, including
interactions between predators and prey, their role in food webs and other
ecological functions, disease transmission, allergies and interaction with
humans or other animal species;
(b)
Consequences resulting from combinatorial and cumulative effects in the
likely potential receiving environment;
(c)
Relevant knowledge and experience with the LMO in
similar receiving environments;
(d)
Results from laboratory experiments examining, as
appropriate, dose-response relationships or particular effect levels (e.g., EC50, LD50) for acute, chronic or sub-chronic
effects including immunogenic effects;
(e)
Results from field trials evaluating, for instance,
potential invasiveness; and
(f)
Possible consequences of transgene introgression
resulting from outcrossing to sexually compatible species.
›› See references relevant to
“Step 3”:
Step 4: “An estimation of the
overall risk posed by the living modified organism based on the evaluation of
the likelihood and consequences of the identified adverse effects being
realized.”
Rationale:
The purpose of this step,
which may also be referred to as “risk characterization”, is to determine and
characterize the overall risk of the LMO. This can be achieved by
characterising individual risks on the basis of an analysis of the potential
adverse effects completed in step 1, their likelihood (step 2) and consequences
(step 3), and combining them into an overall risk, taking into consideration
any relevant uncertainty that was identified in each of the preceding steps and
how it could affect the estimation of the overall risk of the LMO (see
“Identification and consideration of uncertainty” under “Overarching issues in
the risk assessment process” above).
To date, there is no universally accepted approach for
estimating the overall risk but rather a number of approaches are available for
this purpose. For example, the characterization of the overall risk often
derives a best estimate of risk from multiple lines of evidence. These lines of
evidence may be quantitatively or qualitatively weighted and combined. Risk
matrixes, risk indices or models may be used for this purpose.
A description of the risk characterization may be
expressed qualitatively or quantitatively. Qualitative terms such as ‘high’,
‘medium’, ‘low’, ‘negligible’ or ‘indeterminate’ (e.g., due to uncertainty or
lack of knowledge) have been used to characterize the overall risk of an LMO.
Parties could consider describing these terms and their uses in risk assessment
guidelines published or adopted by them.
The outcome of this step should include a description
explaining how the estimation of the overall risk was performed.
Points to consider:
(a)
The identified potential adverse effects (step 1);
(b)
The assessments of likelihood (step 2);
(c)
The evaluation of the consequences should the adverse
effects be realized (step 3);
(d)
Risk management strategies (see step 5) that may
affect risk estimates if implemented;
(e)
Any interaction, such as synergism, between the identified individual
risks; and
(f)
Broader ecosystem and landscape considerations,
including cumulative
effects due to the presence of various LMOs in the receiving environment.
›› See references relevant to
“Step 4”:
Step 5: “A
recommendation as to whether or not the risks are acceptable or manageable,
including, where necessary, identification of strategies to manage these risks”
Rationale:
In step 5, risk assessors prepare a report summarizing
the risk assessment process and the identified risks, and provide
recommendation(s) as to whether or not the risks are acceptable or manageable
and, if needed, recommendation(s) for risk management options that could be
implemented to manage the risks associated with the LMO. The recommendation is
made in the context of criteria for the acceptability of risk that were
identified in the planning phase of the risk assessment, taking into account
established protection goals, assessment endpoints and risk thresholds, as well as risks posed by the
non-modified recipient organism and its use.
This step is an interface between the process of risk assessment and the
process of decision-making. Importantly, while the risk assessor
provides a recommendation as to whether or not the risks are acceptable or
manageable, the ultimate decision about whether or not to approve the LMO is up
to the decision maker.
Moreover, the
“acceptability” of risks is typically decided at a policy level and may vary from country to
country.
In evaluating the acceptability of the overall risk of
the LMO, it is important to consider whether risk management options can be
identified that could reduce the identified risks and uncertainties. The need, feasibility and efficacy of the management options, including the
capacity to enact them, should be considered on a case-by-case basis. If such measures
are identified, the preceding steps of the risk assessment may need to be
revisited in order to evaluate how the application of the proposed risk
management measures would change the outcome of the steps.
The recommendation on the acceptability of risk(s)
should take into account any available scientific analysis of potential
benefits for the environment, biodiversity, and human health (e.g., change in
the use of crop protection products, reduction of infections in the case of
mosquitoes), and should
also take into account risks associated with other existing user practices
and habits.
Further, the sources and nature of uncertainty that
could not be addressed during the preceding steps of the risk assessment should
be described in relation to how they could affect the conclusions of the risk
assessment. For assessments where uncertainties could not be addressed, it is imperative
that the difficulties encountered during the risk assessment be made
transparent to the decision makers. In such cases, it may also be useful to
provide an analysis of alternative options to assist the decision makers.
Some
uncertainties may be dealt with by monitoring (e.g., checking the validity of
assumptions about the effects of the LMO on components of the ecosystem and
environment), requests for more information, or implementing the appropriate
risk management options.
Monitoring can be applied as a tool to detect
unexpected and long-term adverse effects. Monitoring can also be a means to
reduce uncertainty, to address assumptions made during the risk assessment, to validate
conclusions of the assessment on a wider (e.g., commercial) level of
application, and to establish a causal link or pathway between LMOs and adverse
effects. Monitoring may also be used to evaluate whether risk management
strategies are being implemented effectively, including whether those
strategies are able to detect potential adverse effects before the consequences
are realized.
The issues mentioned
in the ‘Setting the context and scope’ section may be taken into consideration
again at the end of the risk assessment process to evaluate whether the
objectives that were set out at the beginning of the risk assessment have been
met.
The recommendation(s) are submitted, typically as part
of a risk assessment report, for consideration in the decision-making process.
Points to consider related to
the risk management strategies:
(a)
Existing management practices, if applicable, that are
in use for the non-modified recipient organism or for other organisms that
require comparable risk management and that might be appropriate for the LMO
being assessed (e.g., physical containment, separation from breeding partners, isolation
distances to reduce outcrossing potential of the LMO, modifications in
herbicide or pesticide management, crop rotation, soil tillage);
(b)
Methods to detect and identify the LMO, and their
specificity, sensitivity and reliability in the context of environmental
monitoring (e.g., monitoring for short- and long-term, immediate and delayed
effects; specific monitoring on the basis of scientific hypotheses and supposed
cause/effect relationship as well as general monitoring), including plans for
appropriate contingency measures to be applied if warranted based on monitoring
results;
(c)
Management options in the context of the intended use
(e.g., isolation distances to prevent outcrossing, and the use of refuge areas
to minimize the development of resistance to insecticidal proteins); and
(d)
Methods for evaluating the proposed risk management
and monitoring strategies for feasibility, efficacy and effectiveness.
Points to
consider related to the acceptability of risks:
(e)
Established criteria and thresholds for determining
risk acceptability, including those set out in national legislation or
guidelines;
(f)
Protection goals of the Party, as identified when
setting the context and scope for a risk assessment;
(g)
Any relevant experience with the non-modified
recipient organism(s) or other reference line(s) (including practices
associated with their use in the likely potential receiving environment) which
were used to establish the baseline for
the risk assessment;
(h)
Scientific analyses of potential benefits of the LMO, carried
out using similar principles of sound science as those used throughout the risk
assessment;
(i)
Ability to identify, evaluate and confine adverse
effects in the event that the LMO is released into the environment, as well as
to take appropriate response measures.
›› See references relevant to
“Step 5”:
related Issues
Risk assessment is one input to
decision-making regarding LMOs. Other issues that may be part of the
decision-making process, as appropriate, and that are mentioned in other
articles of the Protocol, include:
- Risk
Management (Article 16);
- Capacity-building (Article 22);
- Public Awareness and Participation (Article 23);
- Socio-economic Considerations (Article 26);
- Liability and Redress (Article 27).
A number of other issues, which are not
mentioned in the Protocol (e.g., co-existence, ethical issues), may also be
taken into account in the decision-making process regarding an LMO in
accordance with a country’s policies and regulations.
