Discussion paper for the Workshop:
How can comparative assessment and substitution become a
feasible tool in authorization of Plant Protection Products to
achieve risk reduction?
8 May, 2007, Brussels, Belgium
Part I: Experience in using the Substitution Principle in
Regulation of Plant Protection Products in Sweden.
Part II: Suggestions for guidance on how to perform comparative
assessment and substitution in practice.
Aim and background
The aim of this workshop is to discuss questions related to the issue of comparative
assessment and substitution as proposed in the Commission proposal (2006) 388 for
Regulation concerning placing of plant protection products on the market. The discussion will
be held on a technical and practical level with the purpose to facilitating the political
decisions on comparative assessment and substitution in the Council. The COM proposal for
comparative assessment and substitution has generated questions regarding both the
interpretation of the criteria as well as the applicability when used in practice implying that
there is a need for further technical discussions and clarifications. We would like to focus on
general problems of managing a comparative assessment and how to decide upon a possible
substitution of a product and consequences.
The intention of this concept in the Commission proposal is to identify candidate substances
for substitution at EU level (art 24) and to perform comparative assessment at Member State
level when authorising the products (art 48). The aim is to reduce risks, by gradually, when
possible, replacing products containing substances of concern by ones of lesser concern in
order to benefit the protection of human health and the environment. This would promote
innovation of new products with low risk profile or reformulation of already existing ones.
The concept of comparative assessment and substitution of active substances or plant
protection products does not form a part of the current Directive 91/414/EEC, apart from the
exception of efficacy. However, Sweden has experience in using the concept of comparative
assessment and substitution since 1986. This experience relates to both substitutions of
problematic products with other products or with non-chemical alternatives as well as changes
in the formulations. With this experience in mind we have tried to make guidance on how the
COM proposal could work in practice and to address some of the questions asked.
In order to be in line with the current proposal we leave out alternative ways of introducing
substitution i.e. at EU-level and on products at farm level.
1
Part I: Experience in using the Substitution Principle in
Regulation of Plant Protection Products in Sweden.
Part II: Suggestions for guidance on how to perform comparative
assessment and substitution in practice.
Table of contents
Part I: Experience in using the Substitution Principle in Regulation of Plant Protection
Products in Sweden. ................................................................................................................... 3
General comments .................................................................................................................. 3
Experiences gained in specific issues..................................................................................... 5
Questions and answers ........................................................................................................... 6
Examples ................................................................................................................................ 9
Part II: Suggestions for guidance on how to perform comparative assessment and substitution
in practice. ................................................................................................................................ 14
Thought starter: practical guidance to a tiered system ......................................................... 16
Example of templates ........................................................................................................... 21
2
Part I: Experience in using the Substitution Principle in
Regulation of Plant Protection Products in Sweden.
The substitution principle is one of the basic principles of Swedish chemicals control. This
paper gives a description on the approach and experience gained on the application of this
principle at the regulatory level for plant protection products in Sweden. It will also try to
answer some of the most frequently asked questions, present some practical examples.
Legal aspekts
Most of the experiences in applying substitution originate from the early 1990, before Sweden
became a full member of the European Union in 1995 and when we had our first review
programme. Comparative assessment is not an option for product authorisation in Council
Directive 91/414/EEC, with the exception of efficacy evaluations1. However, due to
transitional measures and derogations in the directive, Sweden did continue to apply some
national criteria and principles not covered by the directive in the national decision-making
process also after 1995. This was the case for products with substances not yet included in
Annex I.
General comments
Comparative assessment
Substitution is based on comparative assessment, making it possible to demonstrate whether
there is another product or method available for the same use area which:



presents significantly less risk to human and animal health or the environment,
is sufficiently efficacious, also taking into account risk for development of resistance,
can be used without unreasonable economic or practical disadvantages for the user.
To make this approach possible, we did use a procedure in which examination of products
with similar use patterns occurs at the same time. Suitable occasions to follow these
procedures were pesticide review programmes.
When the use area and mode of application were identical between the products being
compared, the exposure conditions could normally be assumed to be the same. These
circumstances gave opportunities to essentially base the comparative assessments on the
intrinsic properties of the active substances.
1
The concept of comparative assessment and substitution already forms a part of the uniform principles for the evaluation
and authorization of plant protection products with regard to efficacy. According to point B 2.1.4.in the uniform principles,
Member States shall evaluate the performance of a plant protection product in comparison with a suitable reference product.
No authorisation shall be granted if the effects or yield responses are not similar to those resulting from the use of suitable
reference products (points C 2.1.2. and 2.1.3.).
3
Significantly less risk
A prerequisite for substitution is the presence of a significant difference between the potential
risks to human and animal health or the environment between the products/methods
compared. If the difference is not significant or is unclear, substitution will not be the
preferred tool for risk reduction. The latter may be the case in situations when an assessment
shows significant differences between two products but on different aspects (health vs.
environment, efficacy vs. health or environment), for which no satisfactory scientific methods
exist to make a reliable comparison.
Significantly less risk may exist either for the entire use area or only for a part of the use area
(certain crops or use situations), leading to different regulatory actions, see example 4.
Special attention was given to products containing substances with significantly higher
hazard/risk with regard to two or more parameters, so-called multiproblem substances,
compared to monoproblem substances.
Sufficiently efficacious and avoidance of resistance
It is important that the alternative(s) is (are) sufficient efficacious in order for the farmer to
cope with pests problems and also not to discredit the use of alternatives. Therefore the
alternative should be on the market and agriculture should have practical experience with the
alternative(s) before substitution is conducted.
To secure sufficient control of a target organism, e.g. to minimise the risk of developing
resistance, it is desirable to have a number of active substances for each crop/pest situation
with different modes of action. Some products may for this reason be indispensable and not
interchangeable. When just a few substances are available, the possibility to remove or restrict
the use of these substances may be limited. In these situations, the applicants will normally
have to justify why their substance/product is indispensable.
Unreasonable economic or practical disadvantages
When considering unreasonable economic and/or practical problems for users to use products
with other active substances or to use non-chemical methods, the magnitude of what is
unreasonable have been compared with the possible benefit for the environment and/or for
human health. This means that big advantages with regard to decreased risks have been
allowed to cost more.
It is important form the farmer’s point of view that the alternatives are sufficiently efficacious
in order not to have decreased yield or unreasonable costs for alternative treatment etc. The
Swedish experience is that it has been possible to pursue because we have always changed to
an alternative that has been on the market for some time. Therefore the risks for economic
disadvantages for the farmer can be estimated and is not unknown. Such risks have to be
considered into a proportionate analysis of pros and cons in all aspects.
A system of authorization with high safety requirements from health and environmental point
of view leads to withdrawal from the market of those substances that can not live up to the
stipulated criteria. Thus, the possible economic disadvantages for the user in our experience,
was the result of the high safety requirements and comparative assessment did not add to that.
4
The reason being that in comparative assessment you always need to find a sufficiently
functional alternative in order to take a substitution decision
However, there is no easy answer to whether substitution can lead to economic disadvantages
or not for farmers, since this depends on several circumstances at the time of decision. One
important circumstance is whether a monopolistic position (only one manufacturer involved)
can arise, leading to increased product prices.
Experiences gained in specific issues
With regard to the registration process
The uncertainties in establishing and using criteria or levels under which one can be sure that
no unacceptable impact will occur have been a strong motive for also applying comparative
assessments in the registration process. As mentioned earlier, comparative assessment can in
principle be based on the intrinsic properties of the substances, assuming that identical
exposure conditions exist (or allowing for differences in exposure). This approach serves
regulators with an effective tool in risk reduction, since it is generally easier to compare and
rank than to quantify potential risks.
A procedure in which examination of all substances/products with similar use patterns occurs
at the same time has proven to be very cost-effective, since it promotes a uniform and
efficient evaluation and decision-making process.
With regard to users
Users expect that neither less efficient pesticides nor more hazardous pesticides than available
alternatives is to be authorised. A changeover from high-risk products to low risk ones, have
generally not, on a long term run, led to higher costs for the user. However, initially this
might be the case if inexpensive high-risk products are withdrawn from the market.
With regard to industry
Application of the comparative assessment not only promotes the use of existing, but also the
development of new, less hazardous alternatives. In a dynamic perspective this is favourable
both for industry and trade, giving incentives for product development and creating markets
for new products, chemical as well as non-chemical. There are many examples in practice on
how manufacturers/applicants with more favourable alternatives from a risk perspective have
been encouraged to establish their products on the market or increase their market share as a
result of regulatory action based on comparative assessments.
5
Questions and answers
1. Why substitute a product considered being acceptable within the meaning of
Directive 91/414/EEC?
The criteria set out in the Uniform Principles are levels expressing a two-dimensional
approach on the acceptability of plant protection products. If considered to comply with
Article 4 a product shall, if used properly, not have any harmful effects on human or animal
health or on groundwater or any unacceptable influence on the environment.
The uncertainties involved in the risk assessments make it very hard to conclude that the use
will not have any harmful effects even if the approval criteria are met. The use of plant
protection products is always associated with certain levels of risks, due to their inherent
properties, and these risks should be reduced to an extent being reasonable when applying a
risk/benefit approach. These facts are strong motives for applying also comparative risk
assessments and to use substitution in the authorisation process.
2. How to prevent a situation where an existing product is removed and a new less
hazardous substitute turn out to have disadvantages when used in practice?
It should be underlined that approval of an existing product will normally not be revoked
immediately as a result of approval of a new less hazardous product. Instead, this can be
carried out at a later stage when the existing product is to be reviewed, which normally gives
time to gain experience on how the new product performs in practice. The comparative
assessment can then be based on a more well-founded file, see example 7.
3. What is the approach when substitution is proposed for an indispensable highrisk product?
If it is impossible to withdraw a high-risk product from the market immediately, or in the near
future on the basis of comparative assessment, a phase-out plan may be set up. It is preferred
to develop and follow up such plans in co-operation between authorities, users, industry and
research institutions.
4. Will the application of the principle end up in a considerable reduction of the
number of products/ substances on the market?
Experiences have showed that for approximately 10 percent of all products that have been
subject to comparative assessment, the authorisation decision was substitution. The main
reason for the relatively low number of substitution cases is that many cases are not clear cut
and that alternatives often also pose risks that do not significantly differ from the candidate
product. Although it has not been the main basis for the decision, comparative assessment has
also played a role in many other decisions, by supporting and facilitating decisions in one way
or another. Even if 10% substitution of the comparative assessment cases seems to be a low
figure it is our experience in Sweden that it has given a substantial and important risk
reduction and also a clear signal to the manufacturer to extend authorisation for less risky
products.
6
5. How many plant protection products will be subject to comparative assessment
and substitution?
Products that fulfils the criteria for substitution
in Annex IV regardless of whether they contain
candidate substances or not
Products subject to substitution
according to Commission proposal
Approved products in
a Member State
Products containing
candidate substances
Figure 1. This figure demonstrates a rough estimate on the amount of products that may be subject to
comparative assessment and possibly substitution. The number of products differs significantly between MS,
depending to a great extent on
 The number of candidate substances being authorised or applied for authorisation in a MS,
 Whether, according to Annex IV, suitable alternatives are available or not for the crop/pest combination
being assessed.
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Number of
products
Possible
alternative
products
Products containing a
candidate substance
risk
Figure 2a. A graph demonstrating the hypothetic distribution of products in a MS and the proportion of
possible products containing a candidate substance in relation to possible alternative products which might
act as substitutes.
Number of
products
risk
Figure 2b. Hypothetic scenario of the distribution of the products in a MS after a number of years of
comparative assessment and substitution has been applied.
8
Examples
Example 1
There is an application for approval of a selective herbicide intended to be used for pre- and
post-emergence weed control in spring and winter cereals. The product contains an active
substance A, belonging to a group of chemically related substances included in herbicide
products approved for use in cereals. The four substances in question have similar properties
with regard to weed control, thus being replaceable with each other. However, assessment of
the environmental properties of the substances also taking into account the main metabolites
revealed that substance A differs significantly from the others, since it is considered to be far
more mobile and degraded more slowly in soil. Substance A is contrary to the other
substances, associated with risk for ground water contamination.
Decision:
Product containing substance A is not approved.
Example 2
There are a few products with different active substances approved for total weed control in
non-crop areas and in willow plantations. Two of the products contain an active substance B,
for which several concerns have been raised during the first review of old substances.
Substance B and the main metabolite show very slow degradation in soil. The metabolite is
also very mobile and frequently detected in ground water monitoring. Furthermore, substance
B is very volatile and has been identified to cause very specific toxic effects in the olfactory
nasal mucosa in experimental animals, giving rice to concerns for operator safety. There is
another substance available on the market for the same use, also sufficiently effective, but
considered to present significantly less risk in all aspects compared with substance B.
Decision:
The two products containing substance B are not re-approved.
Example 3
A product is approved for use as a soil disinfectant. Main use is for the control of potato cyst
nematodes. The active substance included showed high mobility. Long-term studies also
indicate carcinogenic properties. The use is associated with risk for ground water
contamination, which has been confirmed in monitoring. Progress in regional advisory
programmes has at the same time made it possible to reduce the dependence upon soil
disinfectants by promoting other plant protection practices such as crop rotation, use of
resistant crop varieties and by avoiding cultivation of susceptible crops in infected areas.
Adopting these strategies can in the short term involve economic or practical disadvantages
for the farmers. However, crop rotation does have a beneficial influence on the control of
other plant diseases and is a long term strategy in line with an achieving sustainable
agriculture.
Decision:
The soil disinfectant is not re-approved.
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Example 4
An herbicide product is approved for use in cereals and some vegetable crops. It contains an
active substance C showing high persistence in soil, high bio accumulating potential, is
volatile and highly toxic to different groups of aquatic organisms. There are several
alternative products (including five different actives) available on the market considered to be
equally or more efficacious, for use in cereals. However, no equally efficacious alternatives
are available for use on onions, carrots and beans.
Decision:
The use area for the product containing substance C is restricted to onions,
carrots and beans. If better chemical or non-chemical alternatives become available for the
remaining uses, re-approval will not be granted.
Example 5
In a review of existing herbicides it is concluded that four out of a total of six sugar-beet
herbicides containing the same active substance are based on an organic solvent D. The
remaining two are instead based on an oil-miscible flowable concentrate (OF) containing
vegetable oil. Solvent D is known to be a severe irritant to the skin, eyes, nose, and throat of
exposed workers. The OF formulations show significantly better properties with regard to
worker health, but are identical with regard to efficacy compared with the solvent D based
formulations.
Decision:
The four solvent D based products are not re-approved. Re-approvals are only
granted for the two OF formulations.
Example 6
A group of chemically related substances (E) used in potatoes are subjected to phase out
activities due to risks of chronic health effects associated with repeated exposure to farmers
and the probable leakage of a mobile metabolite of health concern to groundwater. These
particular fungicides have dominated the use in potatoes for a very long time in the struggle
against late blight. They are efficacious, show no risk for the development of resistance and
represent relatively low costs in plant protection management. Due to these circumstances, an
immediate ban has not been possible to put into effect without far-reaching negative
consequences on potato production. Out of eight products containing substance E, five are
mono-component formulations and the other three are mixed formulations containing
substance E in combination with substances having other modes of action. A comparative
assessment reveals that the risks associated with the mixed formulations are almost solely
based on their content of substance E. The use of the mixed formulations involves
considerable lower amounts of substance E applied per treatment and also a reduced number
of treatments due to longer treatment intervals, which means a reduced number of occasions
where workers are exposed to substance E. There are also reports indicating that the use of
mixed formulations (mixture between contact and systemic fungicides) is the best chemical
strategy available for control of the new mating type of Phytophthora infestans. Possibilities
for a continued efficient control of late blight are therefore not considered to be affected, if
only mixed formulations containing substance E are approved.
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Decision:
The applications for re-approval of the five mono-component formulations
containing substance E are withdrawn. Re-approvals for a limited period are only granted for
the three mixed formulations in line with the ongoing phase out plan.
Example 7
There is an application for approval of a fungicide product intended for use in cereals. The
product contains an active substance F, which is chemically related to another substance
already approved for the same use. Substance F show significantly better environmental
properties compared to the existing substance, particularly regarding persistence and
bioaccumulation. However, since the new substance is a severe irritant, only a gel formulation
in water-soluble plastic bags is considered to be acceptable. The comparative assessment
leads to an approval of the gel formulation of substance F, with the intention to substitute the
existing chemically related substance at its next periodical review. The gel formulation of
substance F has shown to be sufficiently effective in earlier trials, but after being used in
practice some technical problems become apparent.
Decision:
The application for renewal of the existing chemically related substance is not
rejected. The gel formulation of substance F is voluntary withdrawn by the registration
holder.
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Final remarks and views on Commission proposal
Comparative assessment and substitution are dynamic elements in the authorisation system
that speeds up development towards safer products. It is founded on the presumption that as
long as it is possible to develop even safer products, there will be a motive for measures that
promotes such a development and incentives for manufacturers to strive for safer products.
Experiences gained in countries applying the substitution principle, demonstrate that it is an
effective regulatory instrument in national pesticide risk reduction activities.
The Commissions proposal COM(2006)388 concerning the placing of plant protection
products on the market includes an obligation for Member States to apply comparative risk
assessment at the level of authorisation of plant protection products containing certain
candidate substances. The Council and the European Parliament has also expressed support
for the introduction of comparative assessments for plant protection products. To apply the
principle on the product level has several advantages. It enables Member States to take into
account specific conditions for each crop/pest combination, such as the existence of
alternatives etcetera. The proposal, does also allow for Member States to consider the
existence of non-chemical control or prevention methods during these assessments.
However, based on the experience on using comparative assessment and substitution in
Sweden we have some comments to the Commission proposal.

Many of the substitution cases in Sweden have been formulation specific. Common
cases are substitution of products based on organic solvents in favour of water-based
formulations or substitution of powder with micro granule formulations with the
purpose to reduce exposure by dusting. These regulatory actions have been easy to
conduct and easy to communicate and stimulated manufacturers to come forward with
better formulations. However, there is no option for applying the principle for these
easy cases in the present proposal from the Commission.

A set of hazard and exposure based criteria is proposed to identify candidates for
substitution at EU level. However, all use and exposure patterns in different Member
States will not be at hand when substances are assessed at community level which may
affect the possibility to choose the right candidates.

A practical consequence of the proposed approach is that it could take a very long
time before comparative assessments can be performed in a complete manner. Based
on the assumption that the proposed regulation will enter into force within a few years,
and that the procedure to list candidate substances will be completed when all
substances have been reviewed again (after the first inclusion in directive
91/414/EEC) and assessed if it could be a candidate for substitution. With regard to
the transitional measures, the review of plant protection products taking into account
comparative assessments will take place very gradually (see figure 3) and can be
expected to be in full use only by 2020. The proposed programme of work in article
18 could, however, speed up the system. Another possibility would be if MS on a
voluntary basis could assess if a substance was a candidate according to Annex II:4
and then start comparative assessment for those products containing such candidate
substances as soon as the regulation enters into force. This would give MS a
possibility gain experience in a flexible way.
12
80
70
60
50
40
30
20
10
0
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
Figure 3. Review of active substances after first inclusion in directive 91/414/EEC. Black part indicates when
candidate substances will be identified at EU level also indicating the earliest occasion when comparative
assessment may be required at MS level
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Part II: Suggestions for guidance on how to perform
comparative assessment and substitution in practice.
COM proposal
Candidates for substitution will be identified at the community level and accordance to art. 24
in the new COM proposal (2006) 388 for placing plant protection products on the market.
According to art 48:
MS shall not authorize a plant protection product containing a candidate for substitution
where a comparative assessment weighing up the risks and benefits, as set out in Annex IV (in
the COM proposal (2006) 388) shows that:
a) for the uses specified in the application of an authorised plant protection product, or a
non-chemical control or prevention method, already exists which is significantly safer for
human or animal health or the environment
b) the plant protection product of non-chemical control or prevention method referred to in
point (a) does not present significant economic or practical disadvantages
c) chemical diversity of active substances is adequate to minimise the occurrence of
resistance in the target organism
All three criteria need to be fulfilled i.e. if alternatives are not significantly safer or if there is
risk for resistance if the candidate product is taken off the market the result is that no
substitution should be made.
The purpose of the comparative assessment is to make it possible to avoid substances which
present considerably higher risk than substitutes that are available on the market. Thereby
giving the least implications for the farmers since substitution is only made when an
alternative for the same use is available.
Risk assessment in relation to comparative assessment: General
comments
Every product must be assessed objectively based on criteria common. The risk assessment
includes several different elements, such as hazard identification, dose-response assessment,
exposure assessment and risk characterization.
The risk characterization includes the categorization of the substance as being a substance of
great concern, a substance of concern or a substance of low concern
Comparative assessment is made between products that are intended for the same use (same
crop and pest). In such cases the exposure situation are often similar for the products that are
compared and the estimation of the risk will thus have many similarities which facilitate
ranking of products.
When assessing existing products it is recommendable to evaluate all products for the same
use simultaneously (grouping). This procedure is in fact a cost-effective approach for
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authorities. At the same time it will be possible to make comparative assessments between
products regarding hazard, risk, need etc.
There might be difficulties in making reliable quantitative risk assessments even where
sufficiently accurate data or detailed models could reduce the degree uncertainty. This
problem will remain even without performing a comparative assessment. If, for any reason,
risk assessments are considered very difficult to make a comparative qualitative assessment
may still be possible to perform from hazard assessments based on intrinsic properties of the
substances and the available GAP (dose rate and frequency).
Special consideration should be taken for products containing active substances with
significantly higher hazard/risk for two or more parameters, for instance carcinogenicity and
bioaccumulation, so-called multi-problem substances, compared to other products.
When comparing one product with another the differences in risks to health or the
environment has to be significant if an approval should be refused on the grounds of
comparative assessment.
Some substances/products may pose less risk regarding one environmental parameter while
the substitutes pose less risk with respect to another parameter. If it is not possible to decide
what is the least problematic product then comparative assessment cannot be used.
Comparative assessment in general
The Swedish experience is that only around 10 % of the comparative assessments you start to
do ends up with a substitution. Some cases are obvious – alternatives are lacking. For others
there are too few alternatives to cope with resistance. The efficacy of alternatives is not
sufficient. It may also be quite easy to identify that the difference in risk in not significant or
economic or practical reasons put obvious barriers for substitution.
Below we suggest a simplified procedure to identify around (our estimate) 30% of those cases
where a more precise comparative assessment will be needed. This simplified tiered approach
of comparative assessment could possibly sort out those cases where substitution will not be
possible.
Below we have drafted an approach to a simplified tiered comparative assessment for plant
protection products with the aim to identify those around 30% that need a deeper comparative
assessment in order to try if the product containing a candidate for substitution can be
substituted by alternatives. For the rest a decision not to substitute could be taken already on
this simplified comparative assessment.
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Thought starter: practical guidance to a tiered system
A simplified tiered approach for comparative assessment of plant
protection products containing candidate substances.
Identify product(s) containing an active substance that is a candidate, hereinafter
Candidate Product. The comparative assessment shall compare the Candidate Product
with an alternative plant protection product or method, hereinafter Alternative.
Tier 1
1. Identify the functions of the Candidate Product (i.e. the pest/crop combinations).
a. Identify alternative products with the same functions and use. Compare use
area by use area and pest by pest. According to Art. 54 such information
should be available in each MS electronically. This will greatly facilitate
identification of available alternatives.
b. Identify, where applicable, possible non-chemical control or prevention
methods for the same area of use e.g. crop rotation versus chemical soil
disinfection, chemical weed control versus mechanical weed control methods
etcetera.
 If there are no matching alternatives, stop comparative assessment.
2. Check whether the efficacy is sufficient for the alternative(s). All products under
consideration should already have been assessed according to Uniform Principles
(point B 2.1) for the function for which you are doing comparative risk assessment.
 If the efficacy for all alternatives identified is not sufficient, stop comparative
assessment.
3. Consider the risk for resistance. If the active substance in the Candidate Product has a
similar mode of action as the active substances in the alternative products on the
market, the possibility to combat resistance can be maintained and the comparative
assessment can proceed. However, if the chemical diversity of the active substances is
not adequate to minimise the occurrence of resistance in the target organism the
comparative assessment should not proceed.
 If the chemical diversity of the active substances is not adequate to minimise
the occurrence of resistance in the target organism, stop comparative
assessment.
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Tier 2. A rough estimate of practical or economic disadvantages
1. Some criteria to screen big differences need to be set up which can be judged unrealistic or
economically unfeasible. Possible examples: If the non-chemical method involves lots of
labour it can be judged as unrealistic (economically unfeasible). If a chemical method
increases the farmer’s costs for producing the crop by X%
 If there is obvious significant disadvantages from practical or economic point of view
the comparative assessment should stop at this tier.
Tier 3. Perform comparative risk assessment for health and the
environment
Compare health and environmental risk profiles for the candidate product and the
alternatives. All products under consideration should already have been risk assessed
according to Uniform Principles for the function for which you are doing comparative risk
assessment. Agreed list of endpoints in the review report is used for the active substance
and risk assessment of a product.
1. Identify the GAP i.e. dose rate and frequency and estimate factor exposure. The
application rate of the Candidate Product should be compared to the applications rate
of the alternative products; if similar the factor is 1. The application methods or
techniques should also be listed as well as other factors related to exposure such as
formulation type. Estimate an exposure factor from GAP and formulation differences.
At this point a rough figure is enough to suit the first round of assessment. If
significant risk difference seems to be the case refined estimates would be needed in
the next round
2. Health profile






Identify the routes of exposure important for the area of use in question.
Identify critical effects such as high acute toxicity, sensitization, mutagenicity,
carcinogenicity and reproductive toxicity etc.
List reference values (and NOAEL or LOAELs)
Indicate operator, worker and bystander exposure and risk mitigation
measures.
Indicate consumer exposure
More could be added.
3. Environmental profile:


Identify products with significantly lower PEC/PNEC quotient. Compare riskquotients, PEC/PNEC values for non-target organisms of importance.
Compare other relevant intrinsic properties of the different active substances
such as persistence in the environment, bioaccumulation
17



Possible contamination of groundwater.
Risk mitigation measures.
More could be added.
 If there is no significant risk difference, stop comparative assessment for such
alternative and functions.
4. If an alternative poses a significantly lower risk than the Candidate Product, continue
with comparative assessment. This should imply that it is significantly better with
respect to either health (i.e. consumer and operator) or for the environment and show
no significant difference in the other parameter or is better in both. The significant
differences on the risk profile for the environment could be on completely different
aspects, for which no satisfactory methods exist to make a reliable comparison. This
could be the case if the main problem with the candidate product is the impact on bird
reproduction while for the alternative product it is the risk for groundwater
contamination.
 If an alternative product is significantly more beneficial to health but not to
the environment or vice versa the alternative product is significantly better to
the environment but the health profile is not, then stop comparative
assessment.
Tier 4
For the remaining alternatives (chemical or non-chemical) it has to be demonstrated that:
 The chemical diversity of the active substances remains adequate to minimize
the occurrence of resistance in the target organism
 There seems to be a significant better risk profile based on the comparative
assessment.
 There seems not to be obvious economic or practical disadvantages
Thereafter, conclude or a final/deeper analysis of comparative assessment could be needed in
a second confirmation round.
1. An assessment of the likelihood of increasing risk for resistance.
 If significantly increased resistance is likely, stop comparative assessment.
2. Does a thorough comparative assessment still result in a significant difference in terms
of risks and benefits between the alternative and the Candidate Product?
 If the difference in terms of risks and benefits is not significant, stop
comparative assessment.
3. A more extensive proportionate analysis of the risks and benefits for the farmer and
from an environmental and health perspective should be performed.
If the outcome still is favourable from the point of view of the criteria in article 48 you
decide on substitution.
The advantages of this tiered simplified system is that you may eliminate already in the
beginning those cases when substitution is not the proper instrument to reduce risks since the
assessment does obviously not comply with the criteria in article 48 and Annex IV. It is our
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estimate that by applying this simplified practice you may not need to make a deeper analysis
for more than 20-30% of the possible initial cases.
The possibility to substitute will vary considerably between member states due to availability
of alternatives, differences in pest pressure etc. However cooperation within the zone can
reduce workload in many cases.
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Tier 1.
Identify Candidate Product(s) and possible alternatives
No alternatives
Identify alternatives
chemical and non-chemical
Stop CA
If not sufficient
Check efficacy
Stop CA
OK
If risk for resistance
Check resistance
Stop CA
OK
Tier 2.
A rough estimate of practical or economic disadvantages
If not advantageous
advantageous
Stop CA
Tier 3.
Check of health and environmental hazard and risk profiles
If not equal
Check GAP (for chemical prod.)
Estimate exposure
factor and then
continue simple CA
Roughly equal
Check health and environmental
profiles
If no sign difference
Stop CA
Significant difference
Tier 4.
Socio-economical analysis
beneficial
Substitution
of a Candidate Product to an alternative with less hazard- or risk-profile.
20
Example of templates
Tier 1: comparative assessment for efficacy and resistance…
The approved (or intended) uses for the Candidate Product are for control of late blight in
potatoes, and for control of powdery mildew in tomatoes and cucumbers. Available
alternatives and their efficacy and mode of action indicated. Possible resistance checked.
Product
(mode of action)
Crop /efficacy
Potatoes
OK
Tomatoes
OK
Cucumber
OK
OK
OK
-
Alternative B
(K)
Alternative C
(Z)
OK
-
-
OK
OK
OK
Alternative D
(Z)
OK
OK
OK
Candidate Product
(Z)
Alternative A
(K)
Significant risk for
resistance.
Stop CA
MoA = mode of action of the active substance on the pest (example Z or K), CA = comparative assessment
Summary
2 different MoA
Deeper analysis needed
for possible resistance
continue CA
Tier 3: comparative assessment for health and environmental risk profiles, crop potatoes.
Table all endpoints of interest according to Uniform Principles and GAP for the crop/pest
under scrutiny.
Health profile
Product
Critical
effects
(incl.
increased
SF)
AOEL
ADI
ARfD
Operator,
worker,
bystander
exposure
Consumer
exposure
Classification
Risk phrases
Ranking??
High/low?
Candidate
Product
Alternative
A
Alternative
B
Alternative
C
Alternative
D
AOEL = acceptable operator exposure, ADI = acceptable daily intake, ARfD = acute reference dose, SF = safety
factor
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Environmental profile
Product
Persi
stenc
e
Bioaccumul
Mobility
Critical
TER
Groundwater
PEC/
PNEC
Classific.
Risk
phrases
Ranking?
high/low?
Candidate
Product
Alternative
A
Alternative
B
Alternative
C
Alternative
D
Tier 4: possible substitution, crop potatoes
Summary table of results
Product\CA
Resistance
Health
risk
Environmental
risk
Candidate
Product
Alternat. A
Alternat. B
Alternat. C
Alternat. D
Result
MoA Z
high
medium
MoA K
MoA K
MoA Z
MoA Z
2 different
mod of
actions
Deeper
analysis
needed
low
low
medium
medium
Preliminary
significant
difference
medium
medium
low
medium
Preliminary no
difference
OK
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Economic
assessment
Practical
implications
Conclusion
Substitution
Preliminary
no
difference,
similar cost
Preliminary no
practical
implications
Same application
method, enough
experience of
use. Sufficiently
efficacious
NO