This is a translation of the article: Bewertung von Untersuchungen an Pflanzenschutzmitteln aus der
Marktkontrolle, published in Journal für Verbraucherschutz und Lebensmittelsicherheit (2014) 9: S. 81-92
The original publication is available at http://link.springer.com/article/10.1007/s00003-013-0856-6
Assessment of examinations made of plant protection products taken from the
market
C. Vinke 1
Federal Office of Consumer Protection and Food Safety, Braunschweig
correspondence to: Dr. Claudia Vinke, Bundesamt für Verbraucherschutz und
Lebensmittelsicherheit (BVL), Messeweg 11 – 12, D-38104 Braunschweig, Germany,
Tel.: +49 (0) 531 299 3540, Fax: +49 (0) 531 299 3002, email: [email protected]
received: 14 November 2013, published online 17 January 2014
Keywords: Market control, Plant protection products, Identity, Analytical results, Interpretation
Summary: As part of monitoring the placing on the market of plant protection products, samples
are taken from the market by the competent authorities, by holders of authorisations and by
holders of parallel import permits, and are examined for identity. The issue is whether the
composition of a sample is identical to the composition stated in the application for authorisation
and whether the physical, chemical and technical parameters correspond with the specification
stipulated by FAO/WHO. The status described by Vinke (2009) concerning the assessment of the
identity of plant protection products has undergone a thorough revision. Above all, criteria are
described for assessing the results of studies on plant protection product samples. The revision
was accomplished by the German-speaking working group for plant protection product analysis
(DAPA) and the German-speaking working group for plant protection product formulations
(DAPF).
1 Introduction
Plant protection products cannot be placed on the market and used if they have not run through
an authorisation or approval procedure and been authorised or approved. The authorisation
procedure determines conditions for placing products on the market and for their use. Market
controls check to see whether plant protection products correspond with the composition
1
Joint publication of the German speaking working group for plant protection product analytics (DAPA) and
the German speaking working group for plant protection product formulations (DAPF), www.bvl.bund.de >
Plant Protection Products > Product chemistry
established as a basis at the time of authorisation / approval of parallel trade products. Market
controls are not only carried out by the competent authorities. Authorisation holders or parallel
traders also purchase plant protection products on the market in order to examine them to see
whether they are on the market legally. Each plant protection product intended for sale must
correspond with the defined specification. The examination methods and interpretations
described in Vinke's publication of 2009 have been supplemented and revised in accordance with
the experience which has been gathered since then. Primarily, parameters whose examination is
appropriate are described, and assistance has been provided with regard to the interpretation of
analytical findings. The publication is aimed at laboratories which are operated by authorities and
also authorisation holders or parallel traders who examine samples in the context of their own
market controls or who have them examined by external laboratories. The following test
parameters come into consideration:
•
Contents of active substances and co-formulants
•
Contents of impurities and foreign substances
•
Physical, chemical and technical properties
•
Comparative chromatography and other screening methods
The conclusions, which can be drawn on the basis of current scientific and technological
knowledge by measurements from analytical and physical, chemical and technical test
parameters, were discussed in detail by members of the German speaking working group for
plant protection product analysis (DAPA) and the German speaking working group for plant
protection product formulations (DAPF), including experts from the competent authorities in
Austria, Switzerland and the Federal Republic of Germany, and are presented in detail in this
paper. In particular, the general significance of the test parameters is described and what variation
ranges should be used as a basis for interpreting the findings.
2 Glossary
2.1
Identity
The term 'identity' has several meanings, for example in the context of assessing the marketability
of parallel imports (European Commission 1999, C-100/96 "British Agrochemicals Association"),
assessments as part of the authorisation procedure and the EU evaluation procedure for active
substances according to Regulation (EC) No 1107/2009 (European Commission 2009), (EC) No
544/2011 (European Commission 2011a) and (EC) No 545/2011 (European Commission 2011b),
the approval of parallel trade products according to Guidance Document SANCO/10524/2012
(European Commission 2012), or concerning analytical methods as a way of describing the
qualitative evidence of a substance. In this paper, identity means the conformity of results from
test parameters of a sample with the data laid down at authorisation. The data for parallel trade
products are laid down in the country of origin.
The composition of a plant protection product is decisive for its identity, i.e. the content of active
substance(s), impurities and co-formulants. The composition submitted with the application for
authorisation forms the basis for assessing a plant protection product in all areas, and is also the
basis for the authorisation certificate, and may only be changed by a notification of amendment
(Regulation (EC) No 1107/2009 (European Commission 2009), SANCO/10597/2003, rev. 10.1
(European Commission 2003b), SANCO/12638/2011, rev. 2 (European Commission 2011c)).
Therefore, the composition established in the certificate is used as a basis for examining an
authorised product for identity.
2.2
Reference sample
A reference sample is a sample of a plant protection product which complies with the data laid
down at authorisation. Reference samples are needed, for example, for comparative
chromatography methods. If the sample to be examined is from a plant protection product for
parallel trade it is important to consider that the approval certificate for a product for parallel trade
contains no stipulations regarding its composition; it only determines the Member State from
which the plant protection product can be imported. The active substance contents and maximum
limits for relevant impurities must always be complied with. It should be noted that the composition
in Member States of origin can change with respect to the contents of co-formulants due to
amendments to authorisation such as changed formulations. It may be necessary to take a current
sample from the Member State of origin in order to be able to judge whether a sample complies
with the stated specification.
It is often not possible to source a reference sample from the Member State of origin. In this case,
reference samples can be taken from the importing Member State if need be. As a rule, reference
samples can be provided by the authorisation holder. If this is not possible within an acceptable
period of time, a corresponding product can be bought on the market should a comparative
measurement appear appropriate. However, it should be noted that the sample may not be a
reference sample in the sense defined above should examinations show inadmissible deviations
from the composition associated with the authorisation certificate.
2.3
Co-formulant
Co-formulants or adjuvants are mixtures or substances which provide the plant protection product
with the properties needed for application. Generally they have no biological efficacy such as
active substances, but they are needed to ensure that a plant protection product is easy to handle,
practical to apply and is stable under storage conditions. They can improve operator safety when
preparing the spray liquid and promote the distribution of the active substances in the spray liquid
and on the plants.
2.4
Co-formulant substance
Co-formulants can consist of several elements which are called co-formulant substances. In the
authorisation procedure the exact quantities of all co-formulants contained in a formulation are
laid down together with the co-formulant substances they are made up of. The name (IUPAC,
CA) and CAS and EINECS number must be submitted for each co-formulant substance if
available.
2.5
Impurity
With respect to the technical active substance an impurity is defined as each element apart from
the pure active substance and/or the pure variant as well as additives which can be found in the
technical material (including substances which occur due to the manufacturing process or
degradation during storage).
2.6
Foreign substance
Foreign substances are substances which do not fall into the categories active substances, coformulants or impurities declared by the applicant. These substances have not been evaluated
and are not covered by authorisation or listing. More detailed information can be found in the BVL
publication "Maximum concentration levels for foreign substances in plant protection products"
(BVL 2013).
2.7
Marketability
Plant protection products which are placed on the market must either be authorised or approved
for parallel trade. Only products which comply with the conditions under which authorisation or
approval was granted are classified as marketable. This includes in particular the composition of
the plant protection product.
3 Characterisation of the sample
It is appropriate to perform a characterisation of a sample before proceeding with examination.
Above all, three parameters should be considered in this regard.
3.1
Homogeneity
In particular, liquid plant protection product samples are at risk of separation, for example due to
overlong storage or an unsuitable composition. Separation can result in the formation of a
sediment or of two liquid phases. Sometimes separation is not immediately aparent from the
outside but becomes evident as a result of different densities occuring in the different phases. If
there is still no homogeneous phase in spite of the homogenisation process having run twice, the
plant protection product sample is classified as non-homogenisable. In this case it is not
appropriate to carry out any further examinations, since it is neither possible to take representative
subsamples for analysis nor can it be guaranteed that the product can be applied maintaining a
consistent composition. Consequently, the sample is not acceptable
3.2
Appearance
No generally accepted measuring method exists for determining this test parameter. Therefore,
only a visual evaluation of colour and physical state is possible. This means that a relevant
deviation of the sample to be evaluated compared to the registered product only exists if the
difference is very obvious (e.g. solid - liquid, powder - granular). Less obvious differences, e.g. in
colour (light yellow - yellow) are not sufficient criteria to be able to determine a significant
deviation.
3.3
Density
Density is only determined for liquid formulations. The measuring method has an excellent
reproducibility that enables a quantitative statement. The measuring results from the sample must
not deviate from the authorised product value by more than ± 0.1 g/mL. When measuring density
it must be ensured that air bubbles has dissipated.
4 Analysis of active substances
One of the most important parameters for examining the identity of a plant protection product
sample is the determination of the active substances, both qualitatively and quantitatively. The
relevant analytical methods can be taken either from CIPAC publications (Collaborative
International Pesticides Analytical Council) or the validated analytical methods according to EU
working document SANCO/3030/99 (European Commission 1999) which are submitted to the
authorisation authority as part of the application procedure. Other validated analytical methods
which correspond to current scientific and technical knowledge can also be used.
Admissible deviations from the declared content can be taken from the data in the "Manual on
development and use of FAO and WHO specifications for pesticides” (Food and Agriculture
Organization of the United Nations/World Health Organisation 2010), which are presented in
Table 1.
Table 1 Tolerable deviation between the declared and the actual active substance content in a
plant protection product in accordance with the FAO/WHO manual (2010)
Declared content in g/kg or g/L Admissible deviation from the declared content
at 20 °C ± 2 °C
up to 25
± 15 % for homogeneous formulations (EC, SC, SL, etc.)
± 25 % for heterogeneous formulations (GR, WG, etc.)
more than 25 up to 100
± 10 %
more than 100 up to 250
±6%
more than 250 up to 500
±5%
more than 500
± 25 g/kg or g/L
The tolerance refers to the average analysis result and is for compensating deviations and
accounts for the variations which usually occurs between the batches, when samples are taken
and the variability in analytical determination. It should be noted when interpreting measurement
results that the scatter of results in the test laboratory must lie considerably below the tolerable
deviation used as a basis for interpretation.
If the measured active substance contents lie outside the range stated for the sample in Table 1,
the sample is out of specification.
5 Analysis of co-formulants / co-formulant substances
Co-formulants can be classified according in different ways such as functionality or chemical
structure. Here, putting the co-formulants into groups of lower molecular, oligomeric and
polymeric substances according to their molecular mass is favoured because an increase in
molecular weight means an increase in effort regarding the analytical examination for
identification and quantification and also a reduction in qualitative significance. Whilst lower
molecular co-formulants can, as a rule, be quantified with reasonable analytical input, the analysis
of oligomers (e.g. surfactants) and polymers (e.g. thickeners, resins) requires special instruments
and methods and is time consuming. In addition, corresponding examinations provide only very
limited conclusions and are therefore not recommended.
An admissible range of quantifiable co-formulants is seen as double the range stated in the
FAO/WHO manual (2010) for active substances, since the contents of co-formulants vary more
than those of active substances due to the manufacturing process (Table 2). Just as when
quantifying active substances, the tolerance refers to the average analysis result and takes
account of quantitative deviations between the batches as they normally occur in manufacturing,
sampling and analytical determination. Here it is also important to note that when a measurement
result is interpreted, the scatter of results from the test laboratory must lie clearly below the
tolerable deviation used as a basis for the interpretation.
Table 2 Tolerable deviation between the declared and the actual co-formulant substance content
in a plant protection product (Vinke 2009)
Declared content in g/kg or g/L Admissible deviation from the declared content
at 20 °C ± 2 °C
up to 25
± 30 % for homogeneous formulations (EC, SC, SL etc.)
± 50 % for heterogeneous formulations (GR, WG, etc.)
more than 25 up to 100
± 20 %
more than 100 up to 250
± 12 %
more than 250 up to 500
± 10 %
more than 500
± 50 g/kg or g/L
Many co-formulants are mixtures of several substances, so called co-formulant substances.
When selecting the admissible deviation according to the content in the plant protection product,
it is not the content of the co-formulant that has to be considered, but the content of the coformulant substance.
Example: 110 g/L of co-formulant X is contained in the product and consists to 50 % of coformulant substance A, which means that the product contains 55 g/L of co-formulant substance
A. The value ± 20 % according to Table 2 must be considered as the admissible deviation for the
calculation. The following tolerance values result for co-formulant substance A:
55 g/L (44 g/L – 66 g/L)
If the content of a co-formulant substance is accompanied by "<" in the composition of a coformulant, it does not make sense to state a fluctuation range. Only an upper fluctuation should
be stated, e.g. for a homogeneous formulation:
< 5 g/L + 1.5 g/L (corresponds to a measured maximum value of 6.5 g/L)
If the workload required for the quantification of a co-formulant is too high, a qualitative
determination may be appropriate since even the presence or absence of a substance can
provide information on the composition of a sample. However, it should be noted that such results
often only have an indicative character.
Categories of various co-formulant groups are presented below.
Solvents are typically small-molecule co-formulants, mostly mixtures of hydrocarbon, derived
from mineral oil or fatty acid esters made from natural products (e.g. natural vegetable oils). Due
to their chemical composition, they can be detected and quantified with chromatographic
separation methods, preferably by gas chromatography (GC-FID, GC-MS). Headspace
chromatography has advantages for such analyses. NMR methods are also generally appropriate
as analytical methods for determining substance contents. The method used must be validated
according to SANCO/3030/99 (European Commission 1999), as for all other quantification
methods.
The solvents' contents are not quantified via the single components if they are available as
technical profiles (e.g. aromatic hydrocarbon mixtures) in the plant protection product. In some
cases, sum parameters can be used for quantification.
Solvents stated as single substances in plant protection product formulations (e.g. esters in fatty
acids) are identified and quantified as single components.
Secondary components which are relevant as far as hazardous substances are concerned and
are of particular interest due to their toxicological or ecotoxicological assessment - even if they
are part of a technical profile - are identified and quantified as single components (e.g. benzene,
naphthalene in aromatic hydrocarbon mixtures). Relevant information can also be found in the
safety data sheet. The provisions in the legislation on chemical substances specifying the content
of certain substances must also be taken into account for plant protection products.
Stabilisers aim to protect the product from various influences which cause the degradation of
components. These can include buffer systems, preservatives, antioxidants and active
substance-specific stabilisers.
A difference must be made between degradative stabilisers (e.g. preservatives, antioxidants,
biocides) and non-degradative stabilisers (e.g. buffer systems).
The concentration of stabilisers preventing degradation can decrease with the age of the sample.
A continuous decrease does not necessarily occur. For this reason, it is possible that the content
of stabilisers in market samples is significantly below their nominal value. It is therefore not
appropriate to stipulate a lower limit in these cases.
Water plays a special role in co-formulants. On the one hand, water can be a desired component,
acting as a 'filler' or a continuous phase in the formulation (e.g. SC); in this case the amount is
not relevant in the context of the qualitative differentiation between plant protection products. On
the other hand, it can also occur in formulations as a trace component or impurity (e.g. EC, OD,
WG) and thus have an impact on the appearance, applicability and stability of the formulation or
active substances. In this case the water content is a criterion for the plant protection product
specification.
One possibility of water determination is the Karl Fischer (KF) titration method in the form of
coulometric (small amounts of water) or volumetric analysis (large amounts of water). This method
is characterised by good specificity and precision, short determination periods and a wide
concentration range (see also CIPAC method MT 30). KF titration can be disturbed by aldehydes,
ketones, side-reactions with the titration media or pH-shifts. The combination of KF titration with
an oven can reduce interferences and matrix effects.
Thermal drying is another possible method, e.g. halogen, microwave or infrared drier or drying
cabinet. Apart from water, it should be noted that other components can also evaporate, and that
high temperatures can cause decomposition in the sample material.
Markers are substances which can be added to technical active substances or plant protection
products to authenticate legal products and to identify counterfeit products. The identity of
markers is subject to particular confidentiality. Simple test methods are available for identifying
markers which can also provide an indication of the authenticity of products directly on the market.
These can be requested from the authorisation holder. For definite proof of counterfeit products
these test results have to be supplemented by further laboratory studies.
6 Analysis of impurities, unwanted co-formulants and foreign substances
In addition to the identification and quantification of active substances and co-formulants,
relevant impurities of the technical active substance can also be analysed in a plant protection
product, as stipulated either in Regulation (EC) No 540/2011 (European Commission 2011d) or
by restrictions in the authorisation certificate. Since the compounds are usually small molecules,
they can be determined with standard measurement methods such as GC/FID, GC/MS or
HPLC/UV. Maximum contents are fixed for relevant impurities which must not be exceeded.
The non-conformity limit is the stipulated maximum content for the impurity. However, it should
be noted that a tolerance should also be taken into account in this case for result interpretation,
which accommodates the measurement uncertainty of sampling and analytical determination.
This tolerance should comprise 15 % for homogeneous formulations and 25 % for heterogeneous
formulations where consideration of an inhomogeneous distribution of the analyte in the sample
is needed.
Example: the content of relevant impurity X in active substance Y is 1 g/kg. The content of the
active substance in the plant protection product to be examined, a suspension concentrate, is 550
g/L at a density of 1.000 g/L. This means that the admissible maximum content for the relevant
impurity in the plant protection product is 0.55 g/L with an analytical tolerance of 15 % (0.55 g/L
+ 0.083 g/L) (corresponding to a maximum measured value of 0.63 g/L).
This tolerance can be too narrow for impurities where the maximum limit is reached at very low
concentrations, such as dioxins or nitroso compounds for example, so that a higher value should
be considered. If corresponding maximum limits are not complied with in a plant protection
product, this is evidence that the specification of the plant protection product was not complied
with.
In this case, it is also important to note that when a measurement result is interpreted, the scatter
of the results from the test laboratory must be smaller than the tolerance used as a basis for the
interpretation. If this is not the case, the measurement uncertainty determined in individual cases
must be used as a basis.
Significant impurities in technical active substances can in principle also be determined
analytically in the formulation. However, very special knowledge of the respective technical active
substance is required. In the context of market controls, the contents of significant impurities are
mostly usually determined by authorisation holders. When maximum limits for impurities are
exceeded which were laid down at the time of authorisation via the active substance source, this
can be used as evidence that the sample does not fulfil the specification. This evidence can justify
initial suspicion that the plant protection product is not marketable or not identical if the
corresponding authorised plant protection product was also examined and these results are
consistent with authorisation. When maximum limits are exceeded the same applies as for
relevant impurities. The examination results could also be used for patent infringement
proceedings.
Particular attention should be paid to the examination of unwanted co-formulants. For example,
according to Directive (EC) 2003/53/EC (European Commission 2003a), since January 2005
nonylphenol ethoxylates must not exceed a concentration of 0.1 % in plant protection products
and should be analysed if their presence is possible and analytical methods can be performed
using suitable reference standards. A valid list of unwanted co-formulants for authorisation in
Germany (BVL 2006) can be used as a guide. Furthermore, an Annex III is intended in Regulation
(EC) No 1107/2009 (European Commission 2009) in future, which shall include co-formulants
that are not allowed to be used in the EU.
As far as exceeding maximum limits is concerned, the same also applies as for relevant
impurities.
The presence of substances that are not intended to be a part of the formulation (foreign
substances) also provides information on the assessment of a sample. It is irrelevant whether this
is a result of carry-over from other active substances from the same production plant or whether
they are impurities from co-formulants or significant impurities from the technical active substance
which were not specified. A maximum limit applies to such substances in accordance with BVL
publication "Maximum concentration levels for foreign substances in plant protection products"
(BVL 2013) of 0.1 %. For substances that are very toxic, ecotoxic and/or phytotoxic, even lower
amounts can mean that they are not acceptable. This also applies when a maximum residue limit
for harvested produce cannot be complied with. If corresponding maximum limits are not complied
with in a plant protection product, this is evidence that the specification of the plant protection
product is not complied with. A tolerance of 15 % for homogeneous and 25 % for heterogeneous
formulations should also be taken into account for the interpretation of foreign substance results.
As far as exceeding maximum limits are concerned, the same also applies as for relevant
impurities.
7 Physical, chemical and technical properties
The physical, chemical and technical properties of a plant protection product are not specified in
the authorisation certificate but are determined to a large extent by the composition of the plant
protection product. For example, the surface tension of a product is influenced by the type and
content of the surfactants. For this reason, these characteristics can be used to gain information
on the composition of a sample with relatively little measuring work.
Since some physical, chemical and technical properties of products are subject to change during
storage, the results of storage stability studies by the authorisation holder must also be
incorporated into the assessment. In the approval procedure for plant protection products for
parallel trade, the Member States simply exchange the compositions of the respective plant
protection products. As a rule, information on the differences in their properties resulting from the
various compositions is therefore not available and cannot be used as a basis for decisions. In
these cases, differences in composition therefore merit particular consideration when assessing
the analytical findings.
Physical, chemical and technical properties can be determined with relatively little effort, which
may make complicated analytical procedures for determining the content of certain co-formulants
or co-formulant substances unnecessary. For one, limits can be used which are stipulated in the
FAO/WHO manual (2010) depending on the formulation type (primary criterion) or in a FAO/WHO
specification for an active substance in combination with a certain formulation type. Secondly, the
data submitted for authorisation, including data on storage stability, can be used for performing a
comparative assessment (secondary criterion). Results from a storage study, for example over a
period of 24 months, provide information on the fluctuation range of a test parameter during the
storage of a formulation.
The properties emulsifying behaviour, wet-sieve test, persistent foaming, suspensibility, dust
formation and dispersion stability can be used as primary criteria according to the assessment
criteria in Table 3. If the deviation for one of these test parameters is not acceptable, all in all the
sample does not fulfil the general specification recommended by the FAO. Consequently safe
use cannot be guaranteed.
Table 3 Primary parameters for physical, chemical and technical test parameters depending on the formulation type, stating assessment criteria
Property CIPAC method CS DC EC EG ES EW FS GR ME OD SC SE SG SL SP WG WP WT Assessment criteria
Emulsifying behaviour,
x
x
x
x
Spontaneously emulsifiable: yes
re-emulsifiable: yes
emulsion stability,
e.g. MT 36.3
Wet sieve test,
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x Residue on 75 µm sieve ≤ 2 %
x
x
x ≤ 60 mL (after 1 min), unless there is a
MT 185
Persistent foaming,
x
x
x
x
x
x
x
x
x
MT 47.3
Suspensibility,
warning in the instructions for use
x
x
x
MT 184
x
x ≥ 60 %, determined chemically, unless
there is a requirement (only to be used in
a tank in which the plant protection
product is mixed continuously)
Dustiness,
x
x
x
x
≤ 30 mg (mainly dust-free)
MT 171
Dispersion stability,
x
x
x
x
MT 180
Spontaneously dispersible: yes
re-dispersible: yes
The respective FAO specifications apply in the same way for other formulation types.
Abbreviations: CS Capsule suspension, DC Dispersible concentrate, EC Emulsifiable concentrate (Emulsion concentrate), EG Emulsifiable granule,
ES Emulsion for seed treatment, EW Emulsion, oil in water, FS Flowable concentrate for seed treatment, GR Granule, ME Micro-emulsion, OD Oil
dispersion, SC Suspension concentrate, SE Suspo-emulsion, SG Water soluble granules, SL Soluble concentrate, SP Water soluble powder, WG
Water dispersible granules, WP Wettable powder, WT Water dispersible tablet
Table 4 Secondary parameters for physical, chemical and technical parameters depending on the formulation type, stating assessment criteria
(deviations relative to the data and results of the tests which formed the basis for the authorisation)
Property/CIPAC/EEC
CS DC EC EG ES EW FS GR ME OD SC SE SG SL SP WG WP WT Assessment criteria
method
pH value,
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
MT 75.3
x Acceptable deviation: Fluctuation range
from
the
storage
stability
studies
± 1 pH-unit
Wettability,
x
x
x
x
x
x
x
≤ 60 s, without stirring
MT 53.3
Persistent foaming,
x
x
x
x
x
x
x
x
x
x
x
x
x
MT 47.3
x Acceptable deviation: non-foaming PPP:
max. 5 mL, other PPP: ± 20 mL (after 1 min)
low temperature stability,
x
≤ 0,3 mL separation
MT 39.3
Spontaneity of dispersion,
x
x
x
≥ 60 %
x
≥ 98 %
MT160, MT 174
Attrition resistance,
x
x
x
MT 178
Dilution stability,
x
x
MT 41.1, MT 179.1
Surface tension,
x
MT 41.1: ≤ traces of sediment
MT 179: ≤ 2 % auf 75 µm sieve
x
x
x
x
x
x
x
x
EEC A.5
The respective tolerances apply in the same way for other formulation types.
x
Acceptable deviation: ± 20 %
Further properties can be used for the secondary criteria in compliance with the assessment
criteria in Table 4. However, the data submitted at authorisation are relevant in this case and not
the general FAO specification. If deviations are determined in the secondary criteria, further
examinations should be carried out if appropriate on the plant protection product components in
order to substantiate the suspected significant deviations, since these parameters are only of an
indicative nature. Individual characteristics should generally be determined for concentrations for
which data were also processed for the application for authorisation of the examined plant
protection product. If appropriate, the data before and after storage of the plant protection product
have to be taken into consideration.
If inadmissible deviations are determined, the corresponding CIPAC and EEC methods must be
used and measurements should be taken at least in duplicate.
The test parameters stated are described below.
7.1
Attrition resistance
Attrition resistance is relevant for the safe use of the formulation, e.g. with relation to the formation
of dust due to transport and application. Attrition resistance should be at least 98 %.
7.2
Wettability
Wettability is for assuring that powder and granules become wet quickly when being mixed with
water and do not float on the surface. A product should be wet up within 60 s without stirring. In
certain cases wetting can take longer or the product must be stirred. The corresponding
information in the manufacturer's instructions for use should be taken into consideration.
7.3
Dispersion stability
Dispersion behaviour can be assessed using the criteria of 'spontaneously dispersible' and 'redispersible after 24 hours'. If one of the two results from the tested sample is 'no', this means it
does not comply with the FAO specification. In this case, the product cannot be applied without a
loss of quality since it cannot be guaranteed that the active substance will be distributed evenly
in the solution.
7.4
Emulsifying behaviour
Emulsifying behaviour can be assessed using the criteria of 'spontaneously emulsifiable' and 'reemulsifiable after 24 hours'. If one of the two results from the tested sample is 'no', this means it
does not comply with the FAO specification. In this case, the product cannot be applied without a
loss of quality since it cannot be guaranteed that the active substance will be distributed evenly
in the solution.
7.5
Low temperature stability
Low temperature stability assures that a liquid plant protection product can still be used even if
temperatures are below freezing for a short while, as they sometimes are in winter in pesticide
stores which are not insulated. Following cold storage, separation should be no more than 0.3 mL.
7.6
pH value
The pH assessment of a sample should also take fluctuations into account which are due to plant
protection product storage. Data from storage stability studies on the authorised plant protection
product and resulting fluctuation ranges should therefore be taken into consideration. The pH
value of the sample must not deviate by more than one unit from the pH values before or after
storage.
7.7
Persistent foaming
Persistent foaming is determined according to CIPAC MT 47.3, but only the value after one minute
is used. When it is used as a primary criterion, the foam volume should not exceed 60 mL unless
the instructions for use contain a special warning and corresponding recommendations for
application. In this case a foam volume of > 60 mL does not automatically mean that it is not
acceptable.
When it is used as a secondary criterion, the sample should not show more than 5 mL foam if the
authorised product is described as 'non-foaming'. In all other cases the deviation between the
values of the authorised product and the sample should not be more than 20 mL.
7.8
Spontaneity of dispersion
The spontaneity of dispersion must be determined analytically or gravimetrically, according to the
data submitted for authorisation. It should be at least 60 %. If the plant protection product label
carries a restriction which states that the product must be stirred continuously during application,
a spontaneous dispersion of < 60 % does not automatically mean that it is not acceptable. As far
as the assessment of results is concerned, it should be noted that the reproducibility of this
measurement is poorer than other test parameters such as density or pH value. Measurements
may therefore have to be repeated several times to be able to estimate the fluctuation range
better.
7.9
Dustiness
Dustiness is determined optically or gravimetrically according to the data submitted for
authorisation and must remain in category ≤ 30 mg (mainly dust-free) to ensure safe application.
7.10
Suspensibility
Suspensibility must be determined analytically or gravimetrically, according to the data submitted
for authorisation. It must be at least 60 % (primary criterion). If the instructions for use state that
the plant protection product must be stirred continuously during application, suspensibility < 60 %
does not automatically mean that it is not acceptable. As far as the assessment of results is
concerned, it should be noted that the reproducibility of this measurement is poorer than other
test parameters such as density or pH value. The measurements may therefore have to be
repeated several times to be able to estimate the fluctuation range better.
7.11
Dilution stability
The aim of dilution stability is to ensure the applicability of water-soluble products. Water-soluble
products should turn into largely clear solutions after they are dissolved in water. Only negligible
separation of insoluble material is admissible.
7.12
Surface tension
The differences in measurement values for surface tension between the sample and the
authorised product should not be more than 20 %.
7.13
Other test parameters
In certain cases, other test parameters can be very important criteria too. One example is crystal
modification. If an active substance shows a defined characteristic for this test parameter,
analytically speaking this is a very clear differentiation criterion. However, each case must be
viewed on its own and in detail.
8 Comparative chromatography and other methods
In addition, comparative chromatographic methods, so called screening methods, can be used to
evaluate the specification of a plant protection product sample, particularly when special issues
have to be addressed. Analytical measuring methods are meant by this; which provide the
analysis of the sample composition as a general view without determining single components
quantitatively. In this regard it is important that a reference sample is examined in parallel to the
sample under identical measuring conditions. Only a direct comparison of the results from both
measurements enables conclusions to be drawn on the specification of the sample. The choice
of method always depends on the type of formulation and the composition.
Typical analytical methods for the comparison of substance mixtures are chromatographic
separation methods, such as gas and high-performance liquid chromatography, and their
combination with mass spectrometry (GC/MS, LC/MS). Differences between the sample
examined and the reference pattern can be recorded chromatographically, similarly to a
fingerprint. Whilst gas chromatography is suitable for providing evidence of vaporisable
compounds (such as solvents), many non-vaporisable substances can be analysed using LC/MS.
With these techniques, particularly low molecular and oligomeric co-formulants can be analysed,
and as a result of particular findings, also impurities from technical active substances. As a rule,
peaks above the tenfold background emission should be considered. If the chromatogram of the
examined sample shows additional or less peaks than the reference sample or if there are
significant differences in the intensity of identical peaks, this is an indication that there is a
difference in chemical identity. Especially in the case of novel peaks, it is possible that the sample
contains additional substances compared to the plant protection product evaluated in the
authorisation procedure, which were not assessed concerning their risk to humans and the
environment. However, proof of a significant deviation only exists if the peaks are identified by
further measurements and the contents are determined.
The composition of the examined sample must also be taken into consideration when evaluating
the chromatograms. Solvent mixtures which are fractionally distilled, for example, show deviations
due to production. This also applies to the use of natural products. It does not necessarily impair
the quality of a product, but clear differences can occur in the chromatograms of different batches.
At high active substance concentrations, significant impurities can also produce different signal
patterns if the active substances from the reference sample and the sample under examination
come from different sources. Corresponding information on the sample under evaluation must
therefore be taken into consideration when interpreting the chromatograms.
Moreover, a clear peak, which is detected by one of the screening methods mentioned, can be
assigned to a defined structure if corresponding knowledge and databases are available. Clear
proof does not exist until a substance, which is not permitted in the plant protection product, can
be identified using suitable methods. In addition, a validated quantitative method should be used
for quantification to prove that the content in the sample is outside of the admissible fluctuation
range.
The analysis of stable isotopes is also used as a method of sourcing in the area of plant
protection products. Mostly, the isotopes in water which is added when the plant protection
product is manufactured are analysed, and compared with existing data on the isotope
composition of the water at potential manufacturing locations. In addition, the examination of
characteristic isotopes from other product components, mainly from active substances, which
accumulate particular isotopes during synthesis, is used for sourcing plant protection products.
At the moment this technique is particularly significant because it enables authorisation holders
to recognise patent infringements and counterfeit products. The bases for founded statements
are however extensive comparative databases for the corresponding product components. If
deviations are detected in the isotope pattern, this is an indication that the examined sample does
not fulfil the specification or comes from another source.
Additional chromatographic separation methods and/or spectroscopic methods are necessary for
some co-formulants in order to make statements on possible deviations to the reference sample.
In these cases, the kinds of methods or techniques used depend to a large degree on the specific
composition and the substance classes contained in the formulation. Examples, which can also
lead to a statement on the specification of the sample in combination with GC/MS and/or LC/MS
screening, are techniques like atom spectroscopy, thin-layer chromatography, gel permeation
chromatography, infrared spectroscopy, nuclear resonance spectroscopy and microscopic
methods. Again, only identified and quantified substances can be used as evidence of significant
deviations.
If special product knowledge is available, priority can be given to one or more specific analytical
methods rather than one or more screening methods. This applies in particular to co-formulants
or impurities in the technical active substances in the formulation. Chromatographic techniques
such as GC/MS, LC/MS, GC/FID and HPLC/UV are also often used for this purpose. Using
headspace analysis, a multitude of solvents can be determined without this having a strong
influence on the matrix.
References
BVL (2006) List of unwanted substances in plant protection products, BVL website.
http://www.bvl. bund.de under Plant Protection Products, Product Chemistry
BVL (2013) Maximum concentration levels for foreign substances in plant protection products
http://www.bvl. bund.de under Plant Protection Products, Product Chemistry
CIPAC Handbooks, published by Collaborative International Pesticide Analytical Council Ltd.,
printed by Black Bear Press Ltd., Cambridge. http://www.cipac.org
European Commission (1999) Working Document Technical Materials and Preparations:
Guidance for generating and reporting methods of analysis in support of pre- and
post- registration data requirements for Annex II (part A, Section 4) and Annex III
(part A, Section 5) of Directive 91/414/EEC (SANCO/3030/99)
European Commission (2003a) Directive 2003/53/EC of the European Parliament and of the
Council of 18 July 2003 amending for the 26th time Council Directive 76/769/EEC
relating to restrictions on the marketing and use of certain dangerous substances
and preparations (nonylphenol, nonylphenol ethoxylate and cement)
European Commission (2003b) Guidance Document on the assessment of the equivalence of
technical materials of active substances regulated under Regulation (EC)
No.1107/2009 (SANCO/10597/2003, rev.10.1)
European Commission (2009) Regulation (EC) No 1107/2009 of the European Parliament and of
the Council concerning the placing of plant protection products on the market and
repealing Council Directives 79/117/EEC and 91/414/EEC
European Commission (2011a) Regulation (EU) No 544/2011 of the Commission implementing
Regulation (EC) No 1107/2009 of the European Parliament and of the Council as
regards the data requirements for active substances
European Commission (2011b) Regulation (EU) No 545/2011 of the Commission implementing
Regulation (EC) No 1107/2009 of the European Parliament and of the Council as
regards the data requirements for plant protection products
European Commission (2011c) Guidance Document on significant and non-significant changes
of the chemical composition of authorised plant protection products under
Regulation (EC) No 1107/2009 of the EU Parliament and Council on placing of plant
protection products on the market and repealing Council Directives 79/117/EEC and
91/414/EEC (SANCO/12638/2011, rev. 2)
European Commission (2011d) Implementing Regulation (EU) No 540/2011 of the Commission
implementing Regulation (EC) No 1107/2009 of the European Parliament and of the
Council as regards the list of approved active substances
European Commission (2012) Guidance document concerning the parallel trade of plant
protection products (SANCO/10524/2012, vers. 4)
FAO/WHO (2010) Manual on Development and Use of FAO and WHO Specifications for
Pesticides, November 2010 - second revision of the First Edition (available on the
Internet:
http://www.fao.org/agriculture/crops/core-themes/theme/pests/jmps/manual/en )
Vinke C (2009) Beurteilung der Identität von Pflanzenschutzmitteln aus der Marktkontrolle
(Evaluationg the identity of plant protection products by market monitoring)
J Verbrauch Lebensm 4(1):23–30