3.1 New and periodic review compounds
3.2 Reconsideration of previous recommendations
3.3 Data requirements for ERL estimation
The JMPR is not a Regulatory Body and therefore cannot "require" (in the strict sense of the word) submission of data. However, it can and does refrain from estimating maximum residue levels when data are inadequate. In addition, the JMPR publishes list of those data which it considers "desirable" when these are found to be lacking or insufficiently addressed in data submissions.
3.1.1 Identity
3.1.2 Metabolism and environmental fate
3.1.3 Methods of residue analysis and stability of pesticide residues in stored analytical samples
3.1.4 Use pattern
3.1.5 Residues resulting from supervised trials
3.1.6 Fate of residues in storage and processing
3.1.7 Residues in food in commerce and consumption
3.1.8 National Maximum Residue Limits
The data and information needed for the evaluation of pesticide residues of new compounds and compounds evaluated within the periodic review programme are outlined in this section.
One objective of the periodic review is to make the best use of the existing database, regardless of the age of the studies. As a result, countries and industry were requested to provide all relevant information irrespective of whether it had been previously supplied. However, experience has shown that some periodic review submissions contain data that are of limited use for estimating maximum residue levels. For example:
· Residue data are frequently provided that do not relate to current good agricultural practice (GAP) and are not accompanied by adequate details of the conduct of the field trial, the handling of the samples or details of the analysis (including associated recovery data).· Residue data have been developed with non-selective analytical methods (e.g. colorimetric analysis or bioassay).
· Lack of information on specifics and conditions of sampling, sample transportation, sample storage and intervals from sampling until storage and storage until analysis.
· Critical supporting studies are frequently not included in the package provided. Critical supporting studies include: metabolism, animal transfer, processing, analytical methods and freezer storage stability studies.
In reviewing the submissions provided for periodic review over the last two years, residue data or studies with obvious deficiencies have been found to be submitted routinely. The usefulness of such information, even as supplementary data, can be judged only on a case-by-case basis when considered in the context of the available database.
In preparing product monographs (working papers) the data submitters should consider the relevance of residue data in the light of current use practices, residue definitions, analytical methods etc., and that only data pertinent to commodities with current or proposed uses should be provided for the consideration of the FAO Panel. If critical supporting studies are not provided, the monograph must include an explanation of why specific critical supporting studies (e.g. processing information) were not provided. In general, studies which fulfil the requirements of modern national registration systems will generally meet the needs of the JMPR.
The headings of this section follow the format of the JMPR evaluations.
3.1.1.1 Physical and chemical properties
3.1.1.2 Formulations
ISO common name
Chemical name
(IUPAC)
(Chemical Abstract)
CAS Registry. No.:
CIPAC No.:
Synonyms:
Structural formula:
Molecular formula:
Molecular weight:
A detailed chemical and physical characterisation of the compound should be provided. This information is included for new compounds and those undergoing re-evaluation as part of the periodic review programme. It serves as guidance for the interpretation of available test data.
Pure active ingredientAppearance:
Vapour pressure: (in mPa at stated temperature)
Melting point:
Octanol/water partition coefficient:
Solubility: (Water and organic solvents at stated temperatures)
Specific gravity: (... g/cm3 at...stated temperature)
Hydrolysis:
Photolysis:
Dissociation constant:
Thermal stability:Technical material
Minimum purity: (in %)
Main impurities: (range of amounts; confidential information will not be presented as such in the JMPR monographs)
Melting range:
Stability:
List of commercially available formulations.
Information is required on:
Animal metabolism
Plant metabolism
Environmental fate in soil
Environmental fate in water/sediment systems
The purpose of conducting metabolism studies is to determine the qualitative metabolic fate of the active ingredient. Many pesticide undergo change during and after application to plants, soil, water and livestock. The composition of the terminal residue must, therefore, be determined before the residue analytical methodology data can be developed and residues can be quantified. The dose level and criteria for identification and characterisation of residue components, including non-extractable residues, are similar to those described in guidelines of registration authorities.
The information should include documentation on the identity of the metabolites and the quantities present. Distinction should be made about the presence of metabolites in the different parts of the plants (surface, leaves, stems and edible root crops), in different animal tissues (fat, muscles, kidneys, liver, egg and milk) and in different soil types. The rate of the formation and disappearance of metabolites in plant, animals and soil must also be investigated.
It is emphasised that all data on animal metabolism have to be provided to both the WHO Expert Group and the FAO Panel of Experts. Normally the WHO Panel will include detailed discussion on the metabolism of small experimental laboratory animals (e.g. rats, mice, guinea pigs, rabbits, dogs, etc.) in their monographs and the FAO Panel will include detailed discussion of the metabolism of larger food animals (e.g. cattle, goats, sheep, pigs and chickens) in their monographs. The required data on plant metabolism should be submitted to the FAO Panel, while the WHO Group wishes to receive only schemes of plant metabolism.
Farm animal metabolism studies are required whenever a pesticide is applied directly to livestock, to animal premises or housing, or where significant residues remain in crops or commodities used in animal feed, in forage crops, or in any plant parts that could be used in animal feeds. In addition to the metabolism studies, separate animal feeding studies (transfer studies) are required for a ruminant and poultry (and sometimes pigs) whenever significant residues (>0.1 mg/kg) occur in items of feed for these animals and the farm animal metabolism studies indicate that residues may occur above the LOD of residue analytical methods carried out with unlabelled compounds (section 3.1.5).
Usually the most important metabolism studies are those involving ruminants and poultry. Normally lactating cows are used but, in the interest of economy, goats are acceptable alternatives. In the case of poultry, chickens are the animals of choice. Except in special cases, it is not necessary to carry out metabolism studies with pigs since information on metabolism in monogastric animal is available from studies with rats. If metabolism in the rat is different from that in the cow, goat and chicken, pig metabolism studies may be necessary.
A high percentage of the administered dose as radiolabelled tracer should be accountable in animal metabolism studies.
Plant metabolism studies are usually required for a minimum of three diverse plants (unless the pesticide is to be used on only one or two crops). If the metabolism in three diverse (dissimilar) crops is similar, then the metabolism in other crops is normally assumed to be similar. However, if the metabolism is different in different types of plants, a metabolism study is required for each type of crop groups (e.g. root vegetables, leafy crops, fruits, pulses and oilseed, cereals) for which use is proposed.
Plant metabolism studies provide information on the approximate level of total residues, identify the major components of the total terminal residue, indicate the route of distribution of residues and its mobility (uptake from soil, absorption by plants or surface residue) and show the efficiency of extraction procedures for various components of the residue.
Studies on environmental fate in soil and in water and water/sediment systems are normally required for all pesticides except those with specific restricted use (e.g. seed treatment, post-harvest application in storage). The availability of relevant studies is essential for the assessment of the potential for residues in food and feeds.
The FAO Panel does not need data on environmental toxicology, but does need studies on environmental fate relevant to the potential for uptake of residues by food and feed crops. The FAO Panel needs to receive the full studies even if some of the data have been submitted to the Environmental Core Assessment Group.
The submitted data should include:
· physical and chemical properties;· metabolism and degradation in soil, identification of metabolites and degradation products, and an indication of their levels;
· persistence of the parent compound and its metabolites or degradation products in soil under aerobic and anaerobic conditions;
· mobility of the parent compound and its metabolites in soil;
· adsorption by various soils;
· hydrolysis rate and products;
· photolysis on soil and plant surfaces and its products;
· crop uptake and bioavailability of parent compound and its major metabolites;
· residues in rotational crops.
Analytical methods should include:
· Specialised methods used in supervised trials and environmental fate studies which were submitted for evaluation;· Enforcement methods.
Analytical methods are required to determine all residue components needed for the residue definitions for compliance with the MRL and for estimation of dietary intake. The major residue components should be determined individually as far as technically possible.
The individual studies should be summarised and clearly outline the compounds determined, the commodities for which the method is recommended, specificity, repeatability of the method, the limit of determination and the range of residue levels for which the method has been validated, the mean recovery and the relative standard deviation of recoveries at each fortification level including the limit of determination, etc.
Information should be submitted to the JMPR not only on the analytical principles used in the supervised trials and experiments but also the whole analytical procedure in detail including a precise description of the portion of sample analysed, tests to prove the efficiency of extraction, recoveries at various levels, limits of determination, limits of detection, chromatograms of samples and controls and a description of how the limit of determination and detection were derived.
When specific techniques and methods have been used to determine residues in supervised trials which are not readily available in average regulatory laboratories (bearing also in mind the laboratories in developing countries), alternative methods suitable for regulatory control of residues should also be provided. The regulatory method should be validated by comparative analyses of samples of typical field treated commodities with both methods.
The regulatory method should be preferably a multi-residue procedure even if its recovery is not as good as that of a specific individual method as, generally, the laboratories do not have sufficient capacity to apply individual methods to look for compounds possibly present. This fact is clearly demonstrated by the published results of national monitoring studies which indicate that compounds recoverable with multi-residue procedures are much more frequently analysed than those requiring individual methods.
In addition to the company methods, published methods suitable for use by regulatory authorities should also be provided. The CCPR may not proceed with an MRL if no published regulatory method is available.
The results of storage stability tests for residues in stored analytical samples of representative substrates should be provided for samples held in storage before analysis. For plant materials, the number of crops depends on the use of pesticides. Typical matrices should be selected to include predominantly water, oil, protein or starch-containing materials. In the case of animal products tissues, milk and eggs should be chosen. The study conditions should reflect those to which the samples from the residue trials have been subjected. Where sample extracts have been stored for more than 24 hours prior to analysis, the stability of residues should be demonstrated with recovery studies performed under similar conditions.
Storage stability studies are required because many routes of degradation and dissipation can occur, even under cold storage conditions. Although guidance on proper storage is given, e.g. in the FAO Guidelines on Pesticide Residue Trials to Provide Data for the Registration of Pesticides and Establishment of MRLs, data submissions to the JMPR in the past frequently did not include these types of study, even when samples were stored for periods of 6, 8 or 12 months and even longer. The storage stability studies should be designed in such a way that the stability of residues in the stored samples can be definitely determined. When the analytical method determines a "total residue", storage stability studies should include not only the total residue, but also separate analyses of all compounds which may be included in the residue definitions. To emphasise the importance of information on storage stability, monographs now include a new sub-section under "Methods of Residue Analysis entitled Stability of Pesticide Residues in Stored Analytical Samples".
It is essential, that complete current GAP information on pesticides under consideration is always made available to the JMPR. The GAP information should be presented in a systematic manner according to the standardised format(s) given in this Guide. The formats were developed principally for applications on agricultural and horticultural crops; other appropriate formats will need to be used for reporting special GAP data, e.g. post-harvest treatments, seed dressing and animal treatments. The information should be presented in such a way as to facilitate comparison with supervised trial conditions.
GAP summaries are intended as an aid to the evaluation of submitted data and are to be provided in addition to certified labels. It is emphasised that original labels have to be provided by the manufacturer(s) (or other data submitters) in addition to the summary information. Furthermore, the original label should be accompanied by an English translation of the relevant sections if it is printed in a language other than English.
The use patterns should be summarised by the manufacturers from two aspects, (1) biological efficacy and (2) formulation and application. The biological efficacy may be described by listing the major pests or diseases controlled, or it can be given in tabular form. In the latter case, the table (Table 3.1.4.1) should contain the commodities, pests controlled and the growth stage of crop when the application(s) is (are) likely to be required.
Information on formulations, application methods and dosage rates should be summarised in tabular form (Table 3.1.4.2.). Specific information relevant to the use according to GAP (such as dosage depending on the pest; specified minimum intervals between repeated applications; total amount of active ingredient which may be applied during the growing season; restrictions on irrigation or aerial application) should be added as a comment or footnote(s).
Governments or responsible national organisations are requested to summarise the GAP information according to Table 3.1.4.3. The entry required under "Country:" is the name of the country whose GAP is listed in the table, which is not necessarily the same as that of the country submitting the information. The table should strictly reflect the information contained on the label. In simple straightforward cases the enclosure of labels may not required, although it is desirable. However, if the use instructions are more complicated than can be shown in the table, or if the reviewer cannot determine if the use instruction is in terms of spray concentration or application rate, the label is essential. In the case of extensions of use that do not appear on the product label (i.e. off-label registrations), a copy of the registration document or its English translation should be provided.
Table 3.1.4.1. Example for summarising biological efficacy data
Information on pests/diseases controlled by terbufos (JMPR 1989)
|
Crop |
Pests/diseases controlled |
Timing of application(s) |
|
Banana |
Aphids, corm borer, corm weevil, nematodes |
2-4 times per year |
|
Cotton |
Soil pests, wireworms |
Furrow treatment at planting |
|
Potato |
Black maize beetle, wireworm |
Furrow treatment at planting |
|
Sugar cane |
Nematodes, pink spittlebug, sugarcane froghopper, West Indian canefly, whitegrubs, wireworm |
Furrow treatment, at planting or side dressing, 4 months PHI |
Table 3.1.4.2. Example for summarising GAP information
Registered uses of folpet on vegetables and cereals.
|
Crop |
Country |
Form ai |
Application1 |
PHI, days | |||
|
|
|
|
Method |
Rate kg ai/ha |
Spray conc., kg ai/hl |
Number |
|
|
Barley |
France |
|
|
1.5 |
|
|
21 |
|
Beans |
Greece |
WP |
foliar |
0.6-1.5 |
0.1-0.25 |
3-4 |
7 |
|
Beans |
Portugal |
WP |
foliar |
0.13 |
1-2 |
7 | |
|
Beans, green |
Spain |
WP |
foliar |
1.6 |
0.16 |
|
21 |
|
Brassica vegetables |
Italy |
WP |
foliar |
0.35-0.40 |
|
|
10 |
|
|
|
|
|
|
|
|
|
|
Lettuce |
France |
WP |
foliar |
0.64 |
|
|
21-412 |
|
Lettuce |
Israel3 |
WP |
foliar |
2.0 |
|
weekly |
11 |
Form: formulation; ai: active ingredient content
1 g: glasshouse use.
2 summer PHI 21 days, winter PHI 41 days.
3 proposed registration.
Suggested abbreviations for footnotes to the GAP table are:
|
a: |
aerial application |
pr: |
proposed registration |
|
fg: |
field and glasshouse use |
st: |
seed treatment |
|
g: |
glasshouse use only |
t: |
table grapes only |
|
gs: |
growth stage restriction |
w: |
wine grapes only |
|
Po: |
post-harvest use |
When different formats are used to report GAP data on special uses (e.g. seed dressing, animal treatment, etc.), they should always include details on the following aspects of the use pattern:
(a) Responsible reporting body
(b) Pesticide names:
ISO-E common name. If other international code names are used, the Standards organisation should be indicated (between brackets), e.g. (British Standards Institute: BSI), (American National Standards Institute: ANSI), (Japanese Ministry for Agriculture, Forestry and Fisheries: JMAF).
If relevant, in addition proprietary name(s) or trade name(s) can be given.
(c) CCPR number of pesticide, if available
(d) Information on the use pattern as described on the approved label. Use rates and concentrations must be explicitly expressed in terms of active ingredient or product.
Table 3.1.4.3. SUMMARY OF GOOD AGRICULTURAL PRACTICES FOR PESTICIDE USES (Application on agricultural and horticultural crops)
|
Responsible body for reporting (name, address) |
: |
Date:.......................... |
|
Pesticide(s) (common name(s)) |
: |
Page:.......................... |
|
CCPR No(s) |
: |
Country:..................... |
|
Trade name(s) |
: |
|
|
Main uses, e.g. insecticide, fungicide |
: |
|
|
Use Pattern |
|
|
|
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 | ||||
|
Crop and/or situation (a) |
F or G (b) |
Pest or group of pests) controlled (c |
Formulation |
Application |
Application rate per treatment |
PHI (days)(k) |
Remarks: (1) | |||||
|
|
|
|
Type (d-f) |
Conc. of ai (i) |
method, kind (f-h) |
growth stage (j) |
number (range) |
kg ai/hl |
water l/ha |
kg ai/ha |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Explanatory notes for Table 3.1.4.3:
(a) In case of group of crops the Codex classification should be used
(b) Outdoor or field use (F), or glasshouse application (G)
(c) e.g. biting and sucking insects, soil borne insects, foliar fungi
(d) e.g. wettable powder (WP), emulsifiable concentration (EC), granule (GR)
(e) Use CIPAC/FAO Codes where appropriate
(f) All abbreviations used must be explained
(g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench
(h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants
(i) g/kg or g/l
(j) Growth stage at last treatment
(k) PHI = Pre-harvest interval
(l) Remarks may include: Extent of use/economic importance/restrictions (e.g. feeding, grazing)/minimal intervals between applications)
General: all information should be presented in English. The information must come directly from approved labels.
Specific notes:
Crop and/or situation
The crop should be described exactly as on the approved label. If the approved label is for use on crop groups (e.g. "citrus" or "orchard trees") this should be the entry in the GAP table. The individual crops included in the national grouping should be identified by their English names (local varieties in brackets) under "Notes" of the table, preferably using the commodity description given in the Codex Classification of Foods and Animal Feeds.
Country
The names of the countries whose GAP data are presented are recorded in English.
Type of pest controlled
The information can be given in the form of the English name of a specific pest or in the form of a "broader" group of related pest species, e.g. powdery mildews, spider mites, lepidopterous yeasts, etc. The use of a Latin name (between brackets) may often provide clarification. The use of very broad classes of pest organisms, such as fungus diseases, insect pests or similar indications, in general provides insufficient information and should be avoided.
Formulation and type of treatment
The formulation of the pesticide product should be presented with the two-letter coding system developed by GIFAP and adopted by FAO and CIPAC. The codes are given in Appendix III. The definition of the terms can be found in the FAO Manual on the Development and Use of FAO Specifications for Plant Protection Products (4th edition).
The concentration of active ingredient in the formulated product has to be presented for liquid formulations in g/l, such as EC (emulsifiable concentrate) or SC (suspension concentrate, also called flowable concentrate) provided that the label instructions give the dosage rate in litres of the formulated product per ha or per 100 litres spray liquid (or in similar measures). The concentration of active ingredient in solid formulations is expressed on a w/w basis as g/kg or % of active ingredient in the solid product.
Application method, timing and number
The type of treatment must be given in sufficient detail, e.g. the type of apparatus used and its output, such as ULV, high volume sprayer, etc. There is often a link between the type of treatment and specific formulations developed for such applications. It has to be recognised that the residue deposit from different types of treatment may differ considerably, e.g. a ULV application may give rise to a larger residue deposit than a high volume application, both with the same amount of active ingredient per hectare.
The residue at harvest consists for the greater part of the residue deposit, applied at the last application. Since the persistence of the pesticide residue may be different in different times of the season, the growing stage at the last application should be recorded. For example, in moderate climate zones the residue decrease of several pesticides in autumn is in general less than in high summer, due to the higher light intensity (UV) and the higher temperature in the latter period. Code numbers used to describe growth stages should be fully explained.
The number of treatments per season, including the normal interval between applications in days. Indicate if the maximum number of treatments per season is a calculated value if this is not specified on the label. Since the treatment intervals, and thus the number of treatments, are often linked to dosage rates, the recommended alternative situations should be clearly indicated, e.g. for scab control on apples dosage A is applied for preventive treatments at 7-8 days interval or a higher dosage B (= about 1.5 × A) with an interval of 10-14 days. The interval between successive applications may have a considerable impact on the amount of residue deposit at a certain time since residues from earlier applications of the pesticides may still be present at the time of a successive treatment.
Application rate
This should always be presented in metric units. Preferably the dosage rates in amounts of active ingredient are expressed in g or kg/ha. When indicated on the label, the maximum amount of active ingredient which can be applied within a growing season should also be indicated. In cases where the indications on the label are given in g/hl or kg/hl (the spray concentration), this spray concentration should be presented and the kg ai/ha equivalent should not be calculated with the average amount of spray liquid used per hectare. If prior compilations included calculated ai/ha values, this fact should be clearly distinguished from labels instructions.
Pre-harvest interval (PHI), in days:
The pre-harvest interval prescribed or recommended and stated on the label should be presented for the commodities concerned. If different PHIs are recommended for the same or similar commodity, e.g. for glasshouse or outdoor grown crops, or in the case of higher dosage rates, the particular circumstances should be clearly indicated. Sometimes the timing is indicated in terms of crop growth stage, e.g. when the pesticide is recommended for use at a very early stage of the crop development, such as bud burst in apple and pears, pre- and post-emergence applications for weed control, etc. In such cases the reference to the growth stage of last application can be extremely helpful to clarify GAP. PHIs included in the GAP table should only be taken from explicit PHI statements on approved labels.
In the case of direct treatment of animals, the withdrawal period or grazing restrictions after application of pesticide should also be indicated.
3.1.5.1 Information and data from livestock transfer (feeding) and external animal treatment studies
3.1.5.2 Information on veterinary uses
Supervised trials serve as the primary source of information for estimating maximum residue levels and calculating International Estimated Daily Intake. This important concept has never been defined in FAO publications before this Manual (see definition, App. II).
The term "supervised trials" covers the application of a pesticide approximating targeted or authorised use methods, care in the whole procedure and reliable experimental design and sampling. Residue trials performed along the lines described in the FAO Guidelines on Producing Residues Data from Supervised Trials are considered by the JMPR as supervised trials. New supervised trials should be planned, implemented, documented and reported according to the OECD (or comparable) GLP principles (OECD, 1992; 1993) or in compliance with national regulations which ensure the quality of residue data.
Maximum Residue Limits are largely derived from residue data obtained from supervised trials designed to determine the nature and level of residues resulting from the registered or approved use of the pesticide. Since this work will usually have been done before registration is obtained, in many cases the trials should be based on the intended registered use. Since the compounds are evaluated by the JMPR after they have been registered by national authorities (see criteria for selecting pesticides for evaluation in Chapter 2), some of the trial data may not be relevant for JMPR evaluations. Therefore only supervised trial data reflecting the current GAPs should be submitted. Residue data should be presented primarily for mature crops at normal harvest. However, where a significant part of the consumable crop is present at the time of application, some residue dissipation studies are required to complement the residue data obtained at normal harvest.
At present there is no internationally agreed minimum data base required for estimating maximum residue levels. The subject is being discussed and elaborated under the auspices of the OECD Pesticide Forum.
For estimating maximum residue levels of pesticide residues in commodities moving in international trade, results of supervised trials representing the typical agriculture practices, growing and climatic conditions prevailing in all exporting countries should ideally be considered. Therefore, it is in the interests of national governments and the responsibility of manufacturer to provide all relevant valid supervised trial data and supplementary information to the FAO Panel in order to ensure that the recommended limits cover the maximum residues arising from the authorised use of a pesticide and a realistic estimate can be made for the long- term intake of residues.
It is emphasised, however, that the JMPR performs the evaluation of the submitted information and estimates maximum residue levels if the database considered sufficient, regardless of whether it represents world wide use or is limited to a region. The number of trials (generally minimum 6-10) and samples is dependent on the variability of use conditions, the consequent scatter of the residue data, and the importance of the commodity in terms of production, trade and dietary consumption. Several residue data should be available from trials, preferably carried out in at least two separate years or at least representative of different weather conditions in accordance, or approximately in accordance, with Good Agricultural Practice. If uses are authorised in regions with substantially different climatic conditions, trials should also be carried out in each region.
To ensure the availability of all detailed information necessary for evaluation, copies of the complete original reports on the supervised trials have to be submitted, preferably in English or with sufficient keys or translation to facilitate review.. In addition, the results of supervised trials should be summarised in the form given in Table 3.1.5.1. The explanations for the entries in the table are the same as those given under "Use pattern" in the previous section. The location of trials should be given by country and region within that country. Names of countries should preferably be recorded in English. An acceptable, but less preferred, alternative is to use the ISO alpha 3 code made up of 3 capital letters (ISO, 1993).
Based on the experience of the FAO Panel, the presentation of the following information in the summary of supervised trials is often insufficient or ambiguous, and needs special attention. The supplementary information and/or explanation of trial conditions can be given as remarks or footnotes.
Description of crop, Other names (varieties or cultivars) can be given in brackets.Dates of application in relation to growth stage and intervals between applications and between last application and sampling. Clear indication of the related dates of multiple applications and sequential sampling is of special importance. Especially important is information on the intervals of handling and storage conditions from sampling to sample storage, and intervals and conditions of sample storage prior to analysis.
Method of application in relation to GAP. Application rate in metric units.
Sampling method should be described in detail, including the number of primary samples in the composite sample and the total weight of composite sample, and the method of preparation of subsamples from a bulk sample. In the case of new trials, the sample sizes given in the FAO Guidelines on Producing Residues Data from Supervised Trials should be followed as far as possible (Appendix V).
Samples taken from replicate plots (in close vicinity and treated on the same day with the same equipment using the same formulation at the same nominal rate) and replicate samples taken from a single plot should be clearly distinguished.
Sample preparation should be carried out according to the Codex Guide on "Portion of Commodities to which Codex MRLs Apply" (Appendix VI). The portion of the commodity which is analysed should be unambiguously described.
Table 3.1.5.1 RESIDUES DATA SUMMARY FROM SUPERVISED TRIALS (Application on agricultural and horticultural crops)
|
Active ingredient |
: |
Crop/crop group |
: |
|
Responsible body for reporting (name, address) |
: |
Submission date |
: |
|
Country |
: |
Page |
: |
|
Content of ai (g/kg or g/l) |
: |
Indoor/outdoor |
: |
|
Formulation (e.g. WP) |
: |
Other al in formulation |
: |
|
Commercial product (name) |
: |
(Common name and content) |
: |
|
Producer of commercial product |
: |
Residues calculated as |
: |
|
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 | ||
|
Report-No.: Location incl. Postal code |
Crop Variety |
Date of (b) |
Application rate per treatment |
Dates of treatment(s) or no. of treatm. and last date |
Growth stage at last treatm. or date |
Commodity, Portion analysed (a) |
Residues (mg/kg) |
PHI (days)(d) |
Remarks: 9 (e) | ||
|
|
|
|
kg ai/ha |
water l/ha |
kg ai/hl |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Explanatory notes for Table 3.1.5.1:
(a) According to Codex Classification/Guide(b) Only if relevant
(c) Year must be indicated
(d) Days after last application (Label pre-harvest interval, PHI, underline)
(e) Remarks may include: Climatic conditions; Reference to analytical method and information on which metabolites are included Note: All entries to be filled in as appropriate
When the residues in edible and inedible portions are analysed separately the mass ratios of the two portions should be reported for each sample. (Very often this information is missing. It should be noted that, for instance, residue data measured in citrus pulp alone are useful for estimating dietary intake but cannot be used for estimating a maximum residue level.)
It is important for the JMPR to be able to clearly identify the portion of commodity in which the residues were determined. For instance, in the case of:
· cereal grains some grains and seeds are still in the husks, and for rice results are often reported on polished rice. (The residue levels are usually considerably different for those sorts of commodities. Furthermore, the rice commodities analysed should be in the form in which they may enter international trade.)· stone fruit, the data should clearly indicate whether it is expressed on the whole commodity without stem or with stone and stem removed.
· animal products, for fat soluble pesticides, the data for meat should indicate whether it is expressed on the whole trimmable fat basis or on extracted or rendered fat and the types of fat involved. If expressed on rendered or extracted fat, the percentage of fat and moisture content in the trimmable fat should be included.
Analysis of samples should be carried out including all residues significant for both residue definitions (MRL compliance and dietary intake assessment). The concentration of residue components should be determined individually as far as technically possible. The concentrations of individual residues should be reported separately. The total residue may be calculated additionally. In the latter case the conversion factors used for the calculation should also be reported.
The recovery values obtained at different concentration levels should be reported, but the residues measured should not be corrected for recovery. If the correction was done by the laboratory, this fact should be specifically mentioned together with the reasons for the correction and the method used for correction.
The analytical replicates (obtained by analysing replicate portions of the same laboratory sample) should be distinguished from results of replicate samples. The average value of the analytical replicates should be included in the summary table (Table 3.1.5.1).
When primary samples are analysed, the weight of the primary samples should be included in the report.
The method of expression of residues should be clearly indicated including, for instance, conversion factors applied, correction for blank or control samples, or recoveries.
The residues in animal feed should be reported on dry weight basis (Chapter 5.5, Expression of Maximum Residue Limits). If it is not expressed on the dry weight basis this should be clearly stated, together with any information on the moisture content.
Data from alternative experiments
It is not possible to carry out supervised trials on all varieties and cultivars of crops, nor even on all crop species on which a pesticide may be used. The resulting lack of residue data from supervised trials led the 1978 JMPR to conclude that certain comprehensive selective surveys, which included many of the essential features of supervised trials, could be of great value in proposing MRLs, and submission of such data for consideration was encouraged. With regard to such selected surveys, information must be available on the use practices leading to the residues in the survey. The 1980 JMPR, in introducing the expression "supervised uses", accepted these residue data as one of the sources for the estimation of maximum residue levels. Such data should be viewed as supplementary to supervised trials data and would assist in extrapolations to minor crops.
The JMPR is frequently confronted with difficulties of not having data available even for important food commodities and especially for commodities grown extensively in tropical regions and developing countries. It has been recognised that the food industry, including plantations and processors, often has information that would be valuable for the estimation of maximum residue levels and every effort should be made and support should be given to enable the data to be made available.
The JMPR considers more broadly based monitoring studies on samples of unknown history to be of little value in setting MRLs. They may be used, however, for the estimation of Extraneous Residue Levels (ERLs, see section 5.4.3).
Animal transfer studies use unlabelled compounds to establish the relationship between levels in feed and likely residues in tissues, milk and eggs.
Livestock transfer studies with poultry, lactating cows (goats) and pigs are generally required where significant residues (>0.1 mg/kg) occur in crops or commodities fed to animals and metabolism studies indicate that significant residues (>0.01 mg/kg) may occur in edible tissues and/or that the potential for bioaccumulation exists. Feeding studies are usually carried out using the parent compound, which is normally the residue of greatest significance on the treated crop. In cases where this is not so, the animal transfer studies should be carried out using a metabolite or a realistic crop residue mixture. In some cases the use of field aged residues is preferable.
When only low levels (<0.1 mg/kg) of residues are found in feed items the anticipated animal dietary burden and the results of the metabolism studies must be considered. The latter may indicate that residues in animal commodities would be well below detection limits and thus further animal transfer studies are not necessary.
Where external treatment of animals is needed, this is best carried out with the formulated product in a manner which reflects the proposed use. When a pesticide may be applied in more than one type of formulation or by more than one mode of treatment, separate studies reflecting the usage or combination of usages are required. If the livestock is exposed to the pesticide both in feed and as a direct treatment, the residue study should reflect the level of residues to be expected from the combined exposure scenarios.
When the use of a pesticide in agricultural buildings is such that restrictions cannot preclude the possibility of residues in meat, milk, poultry or eggs, residue studies should be carried out reflecting the maximum conditions of exposure. Separate studies are required for ruminants (cattle), non-ruminants (swine) and poultry (chicken). The studies should reflect all possible residue transfer routes such as: direct absorption, direct consumption or direct contamination of milk from milking equipment.
General guidance with respect to the role of livestock metabolism and feeding studies in the estimation of Maximum Residue Limits by the JMPR may be found in the FAO Guidelines on Producing Residues Data from Supervised Trials. This guidance or its future updates should be followed in performing animal transfer studies.
According to the above-mentioned FAO Guidelines the feeding study should include a control group, group fed at the level of expected intake and a group dosed with an exaggerated level (3-5x, occasionally a higher level, 10x, may be needed). The latter will allow an estimate of what will happen if the normal level is exceeded, will indicate whether residues are proportionate to the intake and will provide additional data if new uses of the product are introduced.
For these studies, the number of animals in each treated group should be at least 3 for larger animals (cows and goats) and 5-10 for poultry (laying hens). Cows should be in mid-lactation producing an average milk yield, and chickens should be in full egg production before dosing is started.
It is also important that the study period is long enough to reach plateau levels for residues in meat, milk and eggs and to observe the rates of decline of the residue levels when the intake of feed with pesticides has ceased.
The documentation of animal feeding studies should include information on:
· number of animals per feeding group,· weight of each animal,
· nature of the residue or compound being dosed (pure compound, aged residue, mixture of parent and metabolite, etc.),
· dose rates per day (mg compound/kg bw/day or mg compound/animal/day),
· feeding levels (ppm in the feed on a dry weight basis),
· feed intake (dry weight basis),
· description of the feed,
· milk or egg production,
· duration of dosing and withdrawal, times for milk or egg collection and animal slaughter, and
· residue levels in tissues and milk or eggs.
Note:For fat-soluble pesticides in both feeding and direct animal treatment trials, the fat samples analysed should be fully described because residue levels may vary in fat from several fat depots within the body of the same animal. The fat description should include:
· the nature of the fat (e.g., peri-renal, subcutaneous);
· location in the animal body (if more than one possibility); and
· lipid content (rendered or extracted fat may be assumed as 100% lipid).Residue levels of fat-soluble pesticides may also depend on the condition of the animal, which should also be recorded.
When a compound is used both as a pesticide on crops and for direct animal treatments (veterinary uses), full information on approved uses for both purposes and data from residue trials according to the approved uses, together with metabolism data in animals, should be included in the submission to the FAO Panel.
In the case of the first evaluation of a compound or re-evaluation within the periodic review, veterinary uses will be treated in the same way as all other uses. If information is not supplied, the FAO Panel will not recommend MRLs covering veterinary uses for new compounds and will recommend withdrawal of the old MRLs which were based on veterinary uses.
3.1.6.1 Information and data from trials on stored products
3.1.6.2 Information and data on residues in processed food
3.1.6.3 Information and data on residues in the edible portions of food commodities
Once the residue has been identified, information on its fate during storage and processing should be included where available.
When residue data are submitted to the JMPR from treatment on stored products as grains and seeds the treatments are often carried out in a number of stores with variable conditions with regard to temperature, humidity, aeration, etc. Information should be available on the use practice and all the conditions under which the products are kept.
Treatments of grain and other products in store give rise to particular difficulties. Pesticides used for storage vary considerably in stability. In addition to the ambient temperatures, varying from tropical to temperate, moisture content and aeration can influence the rate of disappearance. Application of pesticides can vary from commodities stacked in sacks to automated systems in large-scale silos. In addition, the variability of residues within a store (i.e. intra-store variability) can be particularly high, for instance in situations such as fogged potatoes in box stores. For this reason sampling procedures must be designed to obtain a sample representative of the lot.
The need for data on residues of pesticide in processed food has increased considerably during the past few years. The estimation of International Estimated Daily Intake (IEDI) also requires information on residue levels in processed commodities and in the edible portion of raw agricultural commodities.
Processing studies are required to determine whether residues in raw agricultural commodities (RAC) may be expected to degrade or concentrate during food processing. In certain cases the effect of household cooking operations should also be studied. RAC samples used in processing studies should be field-treated at maximum recommended and/or exaggerated rates to contain sufficient residue levels for the determination of processing factors for the various by-products. Processing studies with spiked samples are not acceptable unless it can be demonstrated that the residue in RAC is entirely a surface residue.
processing factor = residue level [mg/kg] in processed product/residue level [mg/kg] in RAC
The processing factor should be explicitly defined in terms of residue levels. In many cooking operations changes in moisture level cause changes in residue levels which are unrelated to changes in the total amount of residue.
Depending on the type of pesticide and its intended use these data could include studies on the chemical composition and level of residue after:
· storage at normal storage temperatures for typical storage periods
· processing.
The following processing methods have been identified as being widely used by industry and/or by consumers:
· Drying (e.g. dates, figs, grapes)
· Canning (e.g. fruits, vegetables, pineapples)
· Juicing (e.g. citrus juice, tomato juice)
· Milling (e.g. wheat bran, flour, whole meal flour)
· Baking of bread
· Brewing (e.g. hops), wine making (e.g. grapes)
· Oil extraction and refining (e.g. olive oil, rapeseed oil)
· Refining (e.g. sugar)
· Cooking, including boiling, cooking in water (e.g. potatoes, rice, vegetables), frying (e.g. potato, meat) and microwave cooking.
Processing studies should simulate commercial practices as closely as possible.
Usually one or a few processing studies are sufficient for each commodity. However, where the processed product is an important part of the diet at least three studies are normally preferred. It is advisable, in any case, to take and analyse more than one sample from the RAC and the processed fractions.
The section should include all the information on residues in the edible portion of commodities for estimating dietary intake. This information is especially important in the case of crops for which maximum residue levels are estimated for the whole commodity as marketed and whose outer parts, e.g. the peel of bananas, citrus fruits and melons, are normally discarded before consumption or processing. This section should thus represent a summary and conclusions of the information on storage and processing, also taking into account the likely residues in the residue trials.
This section should summarise any available monitoring data (including total diet studies, market basket studies, etc.) relevant to the pesticide under review. This information is of particular interest for further refining of the dietary intake estimates.
Monitoring data are the basis for establishing ERLs for pesticides which have become environmental contaminants (Section 5.4.3).
National MRLs should be reported exactly as they are published. The English translation of the commodity description should be as accurate as possible and must not be converted to the presumably equivalent Codex descriptions. The portion of the commodity to which the MRL applies should be specified if it is different from that recommended by the Codex Guide. The national residue definition should be given.
In the light of new uses of a compound or additional information on its residues the compounds may have to be re-evaluated, in which case all new information, additions or corrections have to be presented.
The new information and data will be mainly related to additional GAP and new data from supervised trials, which enable the JMPR to estimate maximum residue levels and eventually propose MRLs for additional commodities, change of established MRLs or confirm existing MRLs. Other types of information may also be submitted, such as reports about additional metabolites which were unknown at the time when the pesticide was first evaluated; ratio and magnitude of the parent compound and/or the metabolites in additional matrices; new reports about animal feeding studies, improved analytical methods with lower limits of determination and improved ability to differentiate between parent compound and/or between metabolites.
It is emphasised that recommendations of the FAO Panel can only be based on information available to the JMPR, and requests or suggestions from the CCPR for changes of recommendations should always be accompanied by clear statement of the reason for the referral, and must be supported by the data necessary for the JMPR to (re)consider the issue.
The experience of the meeting shows that often the information available to national governments has not been provided to the JMPR. The full documentation available to the governments should been provided to resolve questions referred to the JMPR.
The Extraneous Residue Limit (ERL), for JMPR purposes, refers to a pesticide residue arising from environmental sources (including former agricultural uses) other than the use of a pesticide directly or indirectly on the commodity (Appendix II). ERLs are estimated from residue data generated in food monitoring programmes.
In any proposal for ERLs there should be a clear statement that the pesticide (or any precursor) has no permitted uses on the crop, the animal or animal feeds. If former uses have been discontinued, the date of the withdrawal should be provided.
Evaluation will require monitoring data and supporting information, which should include:
· Country· Year or years
· Commodity description (Codex Classification of Foods and Animal Feeds) and portion analysed
· Pesticide, and residue definition
· Sample classification as import, export or domestic production and consumption
· Statement whether the samples derive from random monitoring or are aimed at a particular problem or situation.
If the number of samples monitored is large, the information should be summarised in categories. For each pesticide/commodity/year, etc. combination, the summary should show the following three categories:
· Number of samples analysed· Number of samples with residues below the limit of determination or the limit of reporting
· Number of samples exceeding current MRL or proposed ERL and, in this category, the individual residue values.
The detailed residue data should be presented in tabular form shown in Table 3.3.1. This format allows comparison with other data or combination with data from other reports (Hamilton et al., 1997).
The results of monitoring programmes where no residues were detected should also be reported to help develop a more complete picture of the extraneous residue situation
Table 3.3.1 Standard format for reporting pesticide residues monitoring data
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Country:......................... |
Residue definition:........................................ |
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Commodity:.................... |
Limit of reporting (LOQ, mg/kg):....................................... |
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Codex or National MRL:............................ | |
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Year |
No. of samples analysed |
No. of residues detected |
No. of residues <LOQ |
Number of samples in residue range (mg/kg)* |
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£ 0.005 |
>0.005 |
>0.01 |
>0.02 |
>0.05 |
>0.1 |
>0.2 |
>0.5 |
>1 |
>2 |
>5 |
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Note: * The residue ranges are to be selected according to the residue levels detected.
