Report of an informal workshop on data evaluation in the estimation of dietary intake of pesticide residues for the JMPR
INTRODUCTION
A Joint FAO/WHO Consultation on Guidelines for predicting the Dietary Intake of Pesticide Residues was held in York, United Kingdom from 2-6 May 1995. The main objectives of the Consultation were to review the existing guidelines and to recommend feasible approaches for improving the reliability and accuracy of methods for predicting dietary intake of pesticide residues. The final published report of this Consultation2 became available in February 1996.
2
Recommendations for the revision of the guidelines for predicting dietary intake of pesticide residues. Report of a FAO/WHO Consultation; World Health Organisation 1995.
An informal Workshop was convened in the Hague, Netherlands from 11th-12th April 1996. Dr W. H. van Eck, of the Netherlands Ministry of Health, Welfare and Sport served as chairman. The Workshop had been arranged at the request of the FAO Panel members in order to consider the consequences of the recommendations of the York Consultation for individual reviewers as well as for the JMPR.
The focus of the Workshop was on the issues relating to the reviews of residue data undertaken by the FAO Panel members.
A list of participants is given. The participants considered a number of working examples on quintozene, dithiocarbamates, parathion-methyl and fenpropimorph, which illustrated issues of interest to the FAO Panel.
OBJECTIVES
The chairman explained that the implementation of the York consultation recommendations would have practical consequences for the way the FAO Panel members carried out their evaluations, how those data would be presented and how consumer risk assessments would be carried out by the JMPR. Guidance was needed for the FAO Panel members as to how recommendations are to be implemented. In addition, criteria need to be established in order to ensure consistency and transparency in the work of the FAO Panel.
The Workshop focused mainly on practical considerations of the application of the York consultation recommendations to the work of the FAO Panel. Discussion centred on the following issues:
· the criteria for the selection of residues trials data used to calculate the Supervised Trials Median Residue (STMR) level.· the presentation in the JMPR monographs of intake related information (eg. median residue levels).
· the approach for dealing with residues at the limit of determination (LOD), also referred to as the limit of quantitation (LOO).
· practical considerations of the cases where the residue definition for consumer risk assessment is different from that recommended for enforcement
· evaluation of data on edible portion and processing (combined supervised trials data with processing information)
· identification of appropriate residue values for acute intake assessments
Guidelines were developed in order to give guidance to the FAO Panel reviewers. In addition, a few general recommendations were made. The Workshop recognised that additional guidelines will need to be developed by the JMPR in the future, as experience is gained by the reviewers.
GUIDANCE TO THE FAO PANEL REVIEWERS ON THE IMPLEMENTATION OF THE YORK CONSULTATION RECOMMENDATIONS
The Workshop recommended that:
Comparability
Residues data from countries are evaluated against the GAP in the country of the trials or a neighbouring country with similar climate and cultural practices.
In identifying the STMR, the trials values selected should be comparable with the maximum registered use (i.e. maximum application rate, maximum number of treatments, minimum PHI) on which the MRL is based.
In establishing comparability of uses in the residue trials to the maximum registered use, the application rates in the trials should generally be no more than ± 25 to 30% of the maximum application rate. Deviations from this should be explained in the appraisal. Similarly, ± 25 to 30% should also be used as a guide for establishing comparability of PHI; however, in this case the latitude of acceptable PHIs will also depend on the rate of decline of residues of the compound under evaluation. Consideration as to whether the number of treatments reported in trials are comparable to the registered maximum number of treatments will depend on the persistence of the compound and the interval between applications. Nevertheless, when a large number of treatments are made in the trials (more than 5 or 6) the residue level should be considered very little influenced by further treatments unless the compound is persistent or the treatments are made with unusually short intervals.
In establishing comparability of residue trials data in which more than one parameter (i.e application rate, number of treatments or PHI) deviate from the maximum registered use, consideration should be given to the combination effect on the residue value which may lead to an underestimation or overestimation of the STMR. For example, a trial result should not normally be selected for the estimation of the STMR if both the application rate is lower (perhaps 0.75 kg/ha in the trial; 1kg ai/ha GAP) than the maximum rate registered and the PHI is longer (perhaps 18 days in the trial, 14 days GAP) than the minimum registered PHI, since these parameters would combine to underestimate the residue. When results are selected for the estimation of STMRs, despite combination effects, the reasons should be explained in the appraisal.
If the residue value arising from a use considered comparable with the maximum registered use is lower than another residue value from the same trial which is within GAP, then the higher residue value should be selected in identifying the STMR. For example, if the GAP specified a minimum PHI of 21 days and the residue levels in a trial reflecting GAP were 0.7, 0.6 and 0.9 mg/kg at 21, 28 and 35 days respectively, then the residue value of 0.9 mg/kg would be selected.
Trials with more than one residue value
In identifying the STMR only one data point should be take from each trial (ie. site location)
Where several residue values have been reported from replicate plots from a single trial (ie. site location) the highest residue should be selected for the purpose of identifying the STMR.
Where several residue values have been reported from replicate analyses of the same field sample taken from a single trial (ie. site location) the mean residue should be selected for the purpose of identifying the STMR.
Rounding of results
In identifying the STMR from a residue trial the actual residue value should be used in the estimation of dietary intake without rounding up or down. This would even be the case where the actual results were below the practical limit of determination considered appropriate for enforcement purposes. Rounding of residue values is inappropriate since the STMRs are used at an intermediate stage in the dietary intake calculation.
Residue definition
The WHO Panel consider routinely indicating in their evaluations which metabolites should be included in the dietary risk assessment.
If it is recommended that the residue definition for the risk assessment is different from that for enforcement, then this is clearly stated in the appraisal.
Close communication should be established between the FAO Panel reviewers and the respective reviewers on the Toxicological and Environmental Groups, on questions such as which metabolites are of toxicological significance, prior to the JMPR meeting.
In tabulating the residue trials data the FAO Panel reviewer should indicate the levels of relevant metabolites separately from those of the parent compound, but in a way which would allow subsequent combination, in order to ensure that changes in the residue definition can be accommodated at the JMPR meeting.
In those cases where it is not possible to finalise the risk assessment at the JMPR (September, year 1) usually because of a change in residue definition, then the MRLs would still be recommended to the CCPR (by way of Codex circular letter for comment at step 3) and the compound would be rediscussed at the following years JMPR meeting (September, year 2). The recommended MRLs together with the conclusion of the risk assessment would be available for the next CCPR (April, year 3).
If two compounds, for which STMRs can be calculated, produce the same analyte in compliance monitoring (eg. CS2 for dithiocarbamates) it is possible to separate the intake assessments, if required, because the intake assessment is no longer based on the MRL but is based on residue data specific to the individual compounds.
Combining of populations of data for the calculation of STMRs
In identifying the STMR, residue data reflecting different countries GAPs would normally be combined. However, if the trials data reflecting different countries GAPs appear to give rise to different populations of data then these data sets should not be combined. In these cases the STMR should be calculated from the population(s) of data which is (are) driving the MRL. In deciding whether the results of trials reflecting different countries GAPs give rise to different populations of residues data, the size of the database reflecting the different countries GAPs should be taken into account.
Residues below the limit of determination
That as a general rule, where all residue trials data are <LOD, the STMR would be assumed to be at the LOD, unless there is scientific evidence that residues are "essentially zero". Such supporting evidence would include residues from related trials at shorter PHIs, exaggerated, but related, application rates or a greater number of applications, expectations from metabolism studies or data from related commodities.
Where there are two or more sets of trials with different LODs, and no determinable residues have been reported in the trials, then the lowest LOD should normally be used for the purpose of STMR selection (unless the residues can be assumed to be essentially zero as given above). The size of the trials database supporting the lowest LOD value should be taken into account in the decision.
Processing, cooking factors and edible portion residue data
In using data on the effects on residue levels of processing or cooking practices, the mean reduction or concentration factor should be applied to the STMR estimated for the raw agricultural commodity as already described. The STMR value estimated in this way for the processed commodity should be referred to as the STMR-P.
If data are available for the residues in the edible portion of the commodity (eg. banana pulp) then a STMR should be estimated directly using the edible portion residue values from maximum registered use trials (as opposed to using pesticide values for the whole commodity).
Acute dietary intake
The attention of the FAO Panel members is drawn to the recommendation that for the purpose of acute risk assessment the MRL, or the highest residue in the edible portion, should be used in estimating dietary intake.
Estimation of MRLs for products of animal origin
In estimating MRLs for products of animal origin, theoretical feed intakes for domestic animals should be calculated using the STMR for each feed item (derived from supervised trials comparable with the maximum registered use), rather than the MRL, together with the maximum feed incorporation rates. This is in conformity with past JMPR decisions.
Estimation of STMRs for commodity groups
Where there are adequate trials data the STMRs should, in principle, be identified for the individual commodities and these values used for the intake assessment. However, where the MRL has been established for a group of commodities (eg. pome fruit) a single STMR should be calculated for the group of commodities.
Presentation of STMRs in the JMPR monographs and report
The GAP(s) on which trials data have been selected for the purpose of identifying the STMR should be clearly identified in the monographs.
In tabulating trials data in the monographs the reviewer should ensure that in addition to the normal underlining of trials data that are within GAP (and therefore have been used for the MRL evaluation), the single residue values selected for the estimation of the STMR should be double underlined.
Information on the residue values on which the STMR is based should not only be identified in the tabulated trials data (see above) but a list of the residue values selected should be included in the appraisal, in numerical order, with the median residue underlined. Where the residue situation is complex (eg. a number of metabolites to be considered) these data may best be tabulated in the appraisal. In addition, the STMR values should be included in the recommendation table in the appraisal and in Annex 1 of the report.
The range for the rates and PHIs used in the selection of residue values for STMR should be clearly identified in the appraisal (eg. trials data with application rates from 1.8 - 3.0 kg ai/ha have been selected).
RECOMMENDATIONS
The Workshop recommended that:
a) The recommendations of the York Joint FAO/WHO Consultation are implemented in full into the work of the JMPR.b) The acronym "STMR" be used in the JMPR monographs and report for the Supervised Trials Median Residue level.
c) The FAO Panel identify STMRs routinely for each commodity as part of all future evaluation of compounds in order to facilitate more realistic estimates of long-term dietary intake.
d) The guidance given in section 3 above is used by the FAO Panel reviewers in their evaluations for the 1996 JMPR.
e) The report of the York Consultation be considered by 1996 JMPR together with worked examples that demonstrate the FAO Panel guidance given in section 3.
f) GAP information when submitted by either the manufacturer or member governments, clearly identify which of the rates and PHIs are statutory conditions of use or taken directly from the product label and which are estimates made by the manufacturer or member governments (eg. whether the application rates in kg ai/ha have been calculated from the kg ai/hl application concentrations).
g) The concepts contained in the FAO Panel guidance, as given in section 3, be incorporated into the draft document currently entitled "FAO Guidelines in the evaluation of pesticide residues data and the estimation of the Maximum Residue Limits in Food and Feed".
OTHER CONSIDERATIONS
As a result of the examination of a worked example for STMR estimation, the Workshop noted that significant residues of HCB may result in commodities following applications of quintozene. When quintozene is re-evaluated by the JMPR, consideration should be given to the risk associated with the residues of the impurity HCB.
The WHO informed the Workshop that in revising the Guidelines for the prediction of dietary intake of pesticide residues, they would include hypothetical worked examples of intake calculations in order to give further guidance to member governments.
LIST OF PARTICIPANTS (in alphabetical order)
Dr U. Banasiak, Chemistry Division, Federal Biological Research Centre for Agriculture and Forestry, Braunschweig, Germany.
Mr S. J. Crossley, Pesticides Safety Directorate, Ministry of Agriculture, Fisheries and Food, York, United Kingdom (Report writer)
Mr D. J. Hamilton, Resource Management Institute, Brisbane, Australia.
Dr J. Herrman, International Programme for Chemical Safety, World Health Organisation, Geneva, Switzerland (WHO Joint Secretary to the JMPR)
Mr F. Ives, Health Effects Division, Office of Pesticides Programmes, Environmental Protection Agency, Washington, D.C., United States of America
Dr F. Kopisch-Obuch, Pesticide Group, Plant Protection Service, Plant Production and Protection Division, FAO, Rome, Italy (FAO Joint Secretary to the JMPR)
Mr G. Moy, GEMS/Food Co-ordinator, Food Safety Unit, Division of Food and Nutrition, WHO, Geneva, Switzerland
Dr W. H. van Eck, Head of Food and Veterinary Policy, Directorate for Public Health, Ministry of Health, Welfare and Sport, Rijswijk, The Netherlands (Chairman)
Dr Y. Yamada, Joint FAO/WHO Food Standards Programme, Food Quality and Standards Service, Food Quality and Standards Service, Food Policy and Nutrition Division, FAO, Rome, Italy
