2.1 Modifications to the agenda
2.2 Prediction of dietary intake
2.3 Relationship between Codex Maximum Residue Limits (MRLs) for pesticide residues, good agricultural practice (GAP), and food safety
2.4 Estimation of extraneous residue limits (ERLs)
2.5 Estimation of group maximum residue levels
2.6 Use by the WHO Core Assessment Group of national evaluations of studies
2.7 Interactions of pesticides
2.8 Environmental Core Assessment Group
The re-evaluation of residue and analytical aspects of phosmet within the CCPR periodic review programme was postponed until 1997 at the request of the manufacturer.
2.2.1 Revised guidelines for predicting the dietary intake of pesticide residues
2.2.2 Calculation of dietary intake of pesticide residues
2.2.3 Estimation of supervised trials median residue levels
2.2.4 Example of STMR estimation: Parathion-methyl
The WHO Secretariat reviewed the development of methods for predicting the dietary intake of pesticide residues. The revision of existing guidelines (WHO, 1989) was the subject of an FAO/WHO Consultation held 2-6 May 1995 in York, United Kingdom. The report of that Consultation (WHO/FNU/FOS/95.11) contained recommendations for improving estimates of dietary intake, most notably the use of supervised trials median residue (STMR) levels in lieu of MRLs in the calculation of International Estimated Daily Intakes (IEDIs). The Consultation also recommended a method for assessing acute hazards posed by the consumption of large portions of food containing pesticide residues. The report was considered at the twenty-eighth Session of the CCPR, which agreed (ALINORM 97/24, para 23) that the draft revised guidelines be included on the agenda for their Session in 1997. The draft revised guidelines will be available in English, French and Spanish to governments before that time.
The WHO Secretariat provided a draft of the revised guidelines to the JMPR and requested comment on the inclusion of the National Theoretical Maximum Daily Intakes (TMDIs), which parallel the international intake assessments. The Meeting agreed that, conceptually, this would be useful, particularly for developing countries; however, it also emphasized that when information was available a best estimate of intake should be derived, using the IEDI method. The Meeting endorsed the report of the York Consultation and noted that many of the recommendations had already been implemented by the JMPR.
The Meeting was also informed of the report of an FAO Panel Workshop held in The Hague in April 1996, where integration of the recommendations of the York Consultation into the work of the JMPR was discussed. Further details of the recommendations of the Workshop are given in Section 2.2.3.
The WHO Secretariat also reported on planning for a Joint FAO/WHO Consultation on Food Consumption and Exposure Assessment of Chemicals, which will be held 10-14 February 1997 at WHO Headquarters in Geneva. The Consultation will follow up certain recommendations of the York Consultation, particularly in the development of regional diets and in addressing issues related to implementation of the recommendation on intake assessment for acute hazards. In addition, the Consultation will consider approaches for extending the methods used for assessing the intake of pesticides to other chemicals considered by Codex, including food additives, contaminants, veterinary drug residues, and nutrients.
TMDIs were calculated for the JMPR by WHO (GEMS/Food) using the methods described in Guidelines for predicting dietary intake of pesticide residues (WHO, 1989), as revised by the recommendations of the York Consultation. When information was available IEDIs were also calculated. The results are summarized in Annex III and will be made available to the 29th Session of the CCPR in April 1997.
The JMPR has established acute reference doses for eight pesticides. While the York Consultation recommended a simple method for assessing short-term intake to compare with acute reference doses, the data and policy decisions that would allow such calculations require further clarification. The Meeting noted that the topic would be discussed at the Joint FAO/WHO Consultation on Food Consumption and Exposure Assessment of Chemicals to be held in February 1997 in Geneva and looked forward to receiving the recommendations of that Consultation.
The Meeting noted that the risk assessment of acutely toxic pesticides required further refinement and invited governments to make available relevant information on national approaches. The Meeting agreed that, when appropriate, the risk assessment of acute hazards should take into account any variability in the individual units in composite samples on which the MRL is based.
1. The main objectives of the Joint FAO/WHO Consultation on Guidelines for predicting the Dietary Intake of Pesticide Residues, held in York, United Kingdom, 2-6 May 1995, were to review the existing guidelines and to recommend feasible approaches for improving the reliability and accuracy of methods for predicting the dietary intake of pesticide residues. The final published report of this Consultation became available in February 1996.
2. An informal Workshop was convened in The Hague, Netherlands, 11-12 April 1996, at the request of FAO Panel members, to consider the consequences of the recommendations of the York Consultation for individual reviewers and for the JMPR, and to convert the recommendations into practical methods for evaluating data.
3. The Workshop focused on the reviews of data undertaken by FAO Panel members and the estimation of supervised trials median residue (STMR) levels. Several general recommendations and 27 specific recommendations for the evaluation of data were made.
4. The present Meeting recognized that as pesticides are used in a wide variety of situations methods for evaluating data must be developed to take into account cases that are not already covered by the suggested procedures. The Meeting considered the report of the Workshop and agreed to support its recommendations, while recognizing that data evaluation is evolving. Most of the recommendations have already been implemented in the work of the FAO Panel.
5. On the basis of practical examples, the Meeting concluded that the recommendations on acute dietary intake and ectoparasite treatments of farm animals might require further development. In addition, the Meeting agreed that the recommendation on the estimation of STMRs and MRLs in animal commodities arising from residues in feed required further consideration. The Meeting agreed that examples and more specific guidance in this area should be developed at the 1997 JMPR.
6. The Meeting agreed that STMR levels that had already been estimated should be used by the JMPR in estimating consumer intakes resulting from long-term dietary exposure. The need for more realistic estimates of the dietary intake of pesticide residues was pointed out in the opening address to the Meeting.
7. Methods for presenting estimated STMR levels are still being developed. The aim is to communicate the results as clearly and unambiguously as possible; experience may indicate that further changes are necessary.
8. A copy of the report of the Workshop (Report of an informal workshop on data evaluation in the estimation of dietary intake of pesticide residues for the JMPR) is included as Annex IV to this report. The Meeting agreed that wide availability of the report of the Workshop would improve the transparency of the JMPR evaluation process and would also provide guidance to national governments.
9. The Meeting recommended that both the general and the specific recommendations of the Workshop be included in future FAO and WHO guidelines.
The 28th Session of the CCPR (ALINORM 97/24, para 46) welcomed the proposal that a fully worked example of intake assessment, prepared by the Codex Secretariat, be presented to the next Session. At the request of the CCPR, the Meeting considered the worked example of parathion-methyl (Parathion-methyl, Estimation of Dietary Intake), which demonstrates the methods used for estimating STMR levels. The STMR levels were combined with information on cultural diets in order to estimate chronic dietary intakes. The example was based on the methods recommended at the Workshop in The Hague, April 1996 (see Section 2.2.3 and Annex IV) and the Meeting confirmed that it reflected the methods used by the FAO Panel at the current Meeting. The Meeting recommended that the example be forwarded to the 1997 Session of the CCPR.
The World Trade Organization (WTO) agreement on the Application of Sanitary and Phytosanitary Measures brought the Codex MRLs for pesticides to the attention of a wide range of government officials and representatives of non-governmental organizations. The questions and comments raised during various discussions indicated that the relationship between Codex MRLs for pesticide residues and the safety of food was not always clear. In order to assist the uniform, correct interpretation of the role and the use of MRLs for pesticide residues in food, the Meeting was requested to clarify the matter.
The 'Codex maximum residue limit for pesticide residues' is the maximum concentration of a pesticide residue (expressed as mg/kg) recommended by the Codex Alimentarius Commission to be legally permitted in or on food commodities and animal feeds. MRLs are based on data from trials conducted according to GAP and foods derived from commodities that comply with the respective MRLs are considered to be toxicologically acceptable (Codex Alimentarius Commission procedural manual, 9th ed. p.61.)
Codex standards, one of which is the MRL for pesticide residues, aim to protect the health of consumers and ensure fair practices in food trade.
The Codex MRLs for pesticide residues are elaborated by the Codex Committee on Pesticide Residues on the basis of the advice of the JMPR, which scientifically evaluates all relevant information on pesticides: their toxicology, metabolism in laboratory and farm animals and plants, environmental fate, and residues in food resulting from their use according to national GAP. The JMPR recommends, when possible, ADIs and Acute Reference Doses (acute RfDs) of pesticides for humans and MRLs for pesticide residues in food and feed commodities.
The residue levels that the JMPR recommends for use as MRLs are estimated by identifying the highest population (range and magnitude) of pesticide residues resulting from treatments according to GAP for which sufficient data are available. MRLs generally apply to primary food commodities when they enter the market.
Good Agricultural Practice (GAP) in the use of pesticides includes the nationally authorised safe uses of pesticides under actual conditions necessary for effective pest control. It encompasses a range of levels of pesticide applications up to the highest authorised use, applied in a manner which leaves a residue which is the smallest amount practicable. (Codex Alimentarius Commission procedural manual, 9th ed., p. 60). Owing to differences in pest infestation, the resistance of pests, and growing conditions, the level of residues remaining in or on food and feed commodities may differ significantly according to geographical location.
Codex MRLs are intended primarily to enforce and control compliance with nationally authorized uses of pesticides on commodities moving in international trade. The definition of a residue for enforcement purposes may rely on only one component of the total residue if it sufficiently reflects the use of the given pesticide, while the inclusion of additional residue components may be necessary for estimating dietary intake or assessing risk.
The procedure used for estimating maximum residue levels means that MRLs are based on the registered uses of a pesticide and are not directly related to the ADI or acute RfD of the pesticide. The acceptability of the recommended limits for a pesticide from the point of view of food safety is assessed by the JMPR by estimating the dietary intake of that pesticide. In estimating the dietary intake all relevant information, such as the residues in each individual commodity for which MRLs are recommended, regional diets, and the effects of processing and cooking, is taken into account. The estimated daily intake is compared with the permissible intake of the residue, calculated from the ADI or acute RfD.
The Meeting noted that the WTO had decided to use Codex MRLs as criteria for the acceptability of food in international trade, and emphasized that it would continue to base its recommendations on the critical assessment of all available scientific knowledge and information based on experimental data. One of its basic scientific principles is to protect human health and the quality of the environment by recommending MRLs that are no higher than necessary to reflect national GAP and to keep residue levels as low as practicable in order to reduce the exposure of consumers and the environment resulting from the use of pesticides.
An 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 the pesticide directly or indirectly on the commodity containing the residue. It is the maximum concentration of a pesticide residue that is recommended by the Codex Alimentarius Commission to be legally permitted or recognized as acceptable in or on a food, agricultural commodity, or animal feed (1990 JMPR report, Section 2.7).
The 1995 report of the JMPR (Section 2.8.2) includes a summary of the general JMPR principles for estimating ERLs. Two views were expressed by governments at the 1996 CCPR on the estimation of ERLs (CX/PR 96/5 Add. 1); a conflicting view was subsequently expressed by a third government. The views emphasized the inclusion or exclusion of 'outliers'.
The Meeting concluded that the meaning of the term 'outlier' should be clear in the context of its use. In the context of ERLs, the JMPR does not consider extreme values to be outliers in a statistical sense, because high residue levels are usually not true statistical outliers but values on the tail of a large distribution. The challenge is to decide when it is reasonable to discard those values in order to reflect the expected gradual decline in the levels of chemicals that are typically subject to ERL estimates, while not creating unnecessary barriers to trade.
Generally, the JMPR considers that the databases needed for estimating ERLs should be significantly larger than those required for the estimation of MRLs, because ERL data do not fit a normal distribution. For example, samples from 598 animals are needed to ensure that the estimated ERLs cover 99.5% of a population, allowing a 0.5% violation rate with 95% confidence (Codex Alimentarius, Vol. II, 2nd Ed., p. 372). As ERL data are derived from the random monitoring of different populations, the JMPR does not normally consider a 'world' population of data, but gives independent consideration to different populations, e.g. of different geographical regions or of different animals, before deciding which data populations might be combined. As noted above, the intention is to avoid unnecessary restrictions to trade.
The JMPR compares data distributions in terms of the likely percentages of violations that might occur if a given ERL is proposed. The JMPR is unaware of any internationally agreed level of violations that is recognized as unacceptable. Generally, the JMPR assumes that violation rates of 0.2-0.5% or greater are unacceptable. The JMPR would welcome views from governments on the levels of violation that are considered unacceptable.
For the reasons given above and on the basis of the approaches to estimating ERLs described in the report of the 1995 JMPR, the JMPR chooses not to endorse the country proposals to include or exclude high values. It is unlikely that governments will give consistent guidance on the use of outliers, and the JMPR cannot be a referee. Another reason is that compounds for which ERLs are estimated are no longer approved for use on agricultural commodities because of existing or previous health or environmental concerns.
It is to be expected that there will be a gradual reduction and/or elimination of residues of the chemicals for which ERLs have been proposed. The JMPR considers that the case-by-case approach described in its 1995 report already accommodates issues that might lead to concern. The 1995 report notes that the reasons for estimating ERLs below the maximum residues reported include discouraging unauthorized uses and encouraging the submission of adequate data. This approach is more likely to be used when the higher residues occur infrequently, and the JMPR attempts to balance its use against unnecessary restrictions to trade if health concerns permit.
Although the JMPR does not use targeted monitoring data for estimating ERLs, it agrees that follow-up studies are important when high residues are found in random monitoring to give a clearer view of the significance of the high levels. If properly conducted, such studies may indicate whether or not the higher residues resulted from intentional unauthorized uses and may allow the identification of areas in which production should be limited or where residue reduction strategies should be implemented.
The above discussion gives some of the reasons for the emphasis placed by the JMPR on the importance of providing complete information for ERL estimates, including possible impacts on trade. For example a better ERL estimate, taking into account trade concerns, was possible in the case of DDT when more extensive data were available. This example also illustrates some of the reasoning and approaches used by the JMPR in estimating ERLs (see DDT, Section 4.8).
The 28th (1996) Session of the CCPR retained a proposal of 2 mg/kg for residues of bromopropylate in citrus fruits at Step 7B, to await an opinion from the JMPR on its general policy on recommending group MRLs as opposed to MRLs for individual commodities (ALINORM 97/24, para 50). Similar issues arose in relation to the proposed MRL for fenbutatin oxide in citrus fruits.
In addition to the purely technical questions on general policy and the adequacy of data for group rather than individual MRLs, the 1996 CCPR also invited the JMPR to comment on the possibility of extrapolating residue data to cover minor crops, especially those of interest to developing countries (ALINORM 97/24, para 101). Although this issue was considered by the 1989 JMPR (report, Section 2.11), it can probably best be further addressed by other means, e.g the development of minimum data requirements under consideration by governments, industry and the Organization for Economic Co-operation and Development (OECD) (1994 JMPR report, Section 2.4; ALINORM 97/24, para 101) or the FAO guidelines on data evaluation (1992 JMPR report, Section 2.7), which are being developed. It will therefore not be considered further in this discussion.
The establishment of group MRLs as opposed to MRLs for individual commodities has long been recognized as an acceptable procedure at both the national and international levels. The use of the approach is a recognition that economics may not justify residue trials on all of the many cultivars and varieties of crops, and health protection will not usually require it. In principle the approach recognizes that adequate data for the major crops of a group may be sufficient.
Historically the JMPR has always approached the issue of group or individual MRLs on a case-by-case basis and that approach is unchanged. The main reasons for this are the many factors which can affect a decision on whether or not to propose a group MRL and the lack of international consensus on criteria. These considerations have prevented the JMPR from developing specific guidance for estimating group MRLs which might be applied at the international level in all situations.
Although such specific guidance is not yet available, some general guidance has been developed and recorded by the JMPR over the years. The JMPR proposed group MRLs at least as early as 1966, but principles for estimating group maximum residue levels were first addressed in some detail by the 1970 Meeting and amplified somewhat in 1973. This was before the existence of any internationally recognized classification of food and feed commodities by groups. The 1974, 1976, 1977 and 1979 Joint Meetings were encouraged by the on-going development of the Codex classification of foods and feeds and recognized the importance of this to the issue of group MRLs. The 1979 JMPR for the first time recorded the use of the Codex Definition and Classification of Food and Feed Groups to define individual commodities and those to which group MRLs should apply.
The 1981 JMPR (report, Section 2.3) expounded in some detail the concepts involved in the extrapolation of data from one crop to another, for both group and individual MRLs. The 1985, 1986 and 1988 Joint Meetings acknowledged the availability of, and reported the continued use of, a new edition of the Codex Classification (CAC/PR4-1985). The continued use of the system by the JMPR since that time is widely recognized.
In order to respond to the request of the CCPR for an explanation of the general policy for estimating group MRLs, the Meeting took into account previous consideration of the issue by the JMPR (particularly the reports of the 1970, 1973 and 1981 Meetings) as well as the collective experience of its members. From these it was possible to summarize a number of general principles and observations which reflect the current views of the JMPR on estimating group MRLs. The following list is intended to supersede previous general guidance by the JMPR for estimating such MRLs.
(a) The JMPR continues to rely on the Codex Classification of Foods and Feeds as the primary definitional basis for recommending MRLs for individual or grouped commodities.(b) The JMPR now generally refrains from estimating maximum residue levels for large Codex 'classes' of foods or feeds such as fruits, vegetables, grasses, nuts and seeds, herbs and spices, or mammalian products, which it has done in the past. Residue data and approved uses are usually more likely to refer to smaller Codex 'groups' such as pome fruits, citrus fruits, root and tuber vegetables, pulses, cereal grains, cucurbit fruiting vegetables, milks, meat of cattle, pigs and sheep, etc. As well as being more likely to be justified by the available data on residues and information on GAP, this is judged to be more in line with national approaches and to afford more accurate estimates of dietary intake.
(c) When adequate residue data are available for only a few primary commodities in a food group, separate MRLs should generally be recommended for each commodity on which the data are considered to be adequate.
(d) In some cases the JMPR may, in the absence of sufficient data for one commodity, use data from a similar crop for which GAP is similar to support estimates of maximum residue levels (e.g. pears and apples or broccoli and cauliflower).
(e) If other considerations permit, data on residues in all or most of the major commodities with the potential for high residues within a group may allow estimates of maximum residue levels to be extrapolated to minor crops in the group. An example of a situation in which other considerations do not permit is that in which the variability of the residue levels is too great, even though data on the major crops within the group are available. A group limit cannot then be established.
(f) When residue levels in a number of commodities in a group vary widely, separate recommendations should be made for each commodity. A limit for a group 'except one or more commodities' which are known to deviate from the norm may be justified (e.g. citrus fruits, except mandarins); in such cases separate MRLs should be estimated for the exceptional commodities.
(g) In order for a group limit to be proposed, not only must residue levels in the major commodities in the group not be too different, but the physical nature and other characteristics of the crops that might influence residue levels, as well as cultural practices and GAP for the individual commodities, must also be taken into account.
(h) Residue data for a crop growing quickly in summer cannot be extrapolated to the same or related crops growing slowly under less favourable conditions (e.g. from summer to winter squash).
(i) In establishing group MRLs, detailed knowledge of the metabolism or mechanism of disappearance of a pesticide in one or more crops must be taken into account.
(j) Group MRLs recommended by the JMPR that generally appear to be acceptable include those for cereal grains (based on data for maize, wheat barley, oats and rice), stone fruits, poultry meat, milks, meat from mammals other than marine mammals, and oilseed.
(k) A group MRL is generally preferred in the case of citrus fruits, but care must be used in estimating a maximum level for the group because of the large variations in fruit size and in the ratio of peel to pulp in view of the propensity for residues of many pesticides to concentrate in the peel. Data on major members of the group are especially important.
Historically, many more Codex limits have been established for citrus fruits as a group (45 pesticides) than for individual citrus fruits (19 pesticides): lemons (2 pesticides); lemons and limes (1); mandarins (4), sweet and sour oranges (8), sweet oranges (1); shaddocks or pomelos (1); and grapefruit (2).
(l) All else being equal, data on a crop picked when immature may sometimes be extrapolated to a closely related species with a lower surface area:weight ratio at the time of the pesticide application which grows quickly to maturity, resulting in a rapid decrease in the ratio of residue to crop weight (dilution by crop growth). Thus estimates of maximum residue levels can be extrapolated from gherkins to cucumbers, but not vice versa.
(m) Individual MRLs can be extrapolated more readily to groups when there is no expectation that terminal residues will occur and when this is supported by studies of metabolism. Examples are early treatments, seed treatments, and treatments of orchard crops with herbicides.
While the JMPR generally adheres to these principles on a case-by-case basis, it recognizes certain difficulties or limitations in the acceptance of group limits at the international level. A primary weakness is the lack of formal criteria or an agreed mechanism to determine the members of a group for which data are needed before a group MRL can be established. One approach that is sometimes used effectively at the national level is to identify commodities of a group (often botanical) that represent both major crops within the group and those most likely to contain the highest residues. The factors used to determine whether a crop is a major or representative member of the group include whether some part or growth stage of it is used for animal feed and its dietary significance as a food or feedstuff.
The premise of this approach is that if data are available for representative crops, and if GAP and cultural practices among the individual members are similar, the residue levels will not vary widely and a maximum residue level can be estimated that will suffice for other members of the group for which no data are available. As noted earlier, this approach constitutes the use of common sense and is more or less dictated by the economics of data generation and evaluation.
While the JMPR recognizes real advantages in this approach, there is unfortunately no consensus at the international level on the selection of representative commodities for estimating maximum residue levels for groups. Similarly, while the JMPR bases its recommendations on the Codex Classification of Foods and Feeds, this classification has not been fully adopted at the national level in most countries.
There is also no international agreement about which are major and minor commodities. The proposed development by the OECD of minimum database requirements may resolve some of these difficulties, and the JMPR would welcome such a development within the framework of Codex or the OECD.
Until there is more international agreement in this area, the JMPR will continue to make judgements on a case-by-case basis, using the general policy summarized above or as it may be subsequently amended.
To make use of work that has been performed by other agencies and organizations and to minimize duplication of effort, the Joint Meeting has been encouraged in recent years to make better use of evaluations of studies that have been prepared by national authorities and other organizations. The Meeting agreed that such evaluations should be used to the extent possible.
Detailed evaluations of toxicological studies have been prepared on four substances addressed by the present Meeting: on tebufenozide by the Canadian Pest Management Regulatory Agency, on 2,4-D by the United States Environmental Protection Agency, and on dimethoate and omethoate by the United Kingdom Pesticides Safety Directorate. Preparation of the monographs on these substances for the Meeting was based on the original reports of the studies and other pertinent information and was aided by reference to the national evaluations. However, the Joint Meeting came to independent conclusions about the substances.
The Meeting encouraged the availability of comprehensive evaluations prepared by national authorities and organizations and recommended that they be used to the extent possible by the WHO Core Assessment Group in the future.
The Meeting was requested at the Twenty-eighth Session of the Codex Committee on Pesticide Residues (ALINORM 97/24, paragraph 97) to consider the possible combined effects of pesticides.
The significance of interactions of pesticides was reviewed by the 1967 JMPR. The 1981 Joint Meeting (report, Section 3.6) gave further consideration to interactions between pesticide residues and concluded that:
(1) Not only could pesticides interact, but so could all compounds (including those in food) to which man could be exposed. This leads to unlimited possibilities, and there is no special reason why the interactions of pesticide residues (which are at very low levels) should be highlighted as being of particular concern; (2) very few data on these interactions are available; and (3) the data obtained from acute potentiation studies are of little value in assessing ADIs for man.
The present Meeting noted that effects are not only potentiated, but sometimes mitigated, when two or more pesticides are administered simultaneously to experimental animals. Although a number of studies addressing this issue has been performed since 1981, those that show non-additive effects have been performed at 'effect doses', which are not relevant to mixtures of residues that may be present on food commodities at levels several-fold lower than effect levels.
A report1 was published recently in which a number of compounds with weak oestrogenic activity were screened in a yeast oestrogen system containing human oestrogen receptor. In this assay, combinations of weak environmental oestrogens were up to 1000 times more potent in human oestrogen receptor-mediated transactivation than any chemical alone. While these results are preliminary, possible potentiation should be investigated further to see if the results can be confirmed and, if so, to ascertain their significance in intact biological systems. It should be kept in mind that the food supply contains many pharmacologically active substances, including phyto-oestrogens. The structures and activities of pesticides give no reason to conclude that they have more oestrogenic activity than many naturally occurring phyto-oestrogens. In addition, any interactions that may occur could result in either antagonistic or synergistic effects.
1 Arnold, S.F., Klotz, D.M., Collins, B.M., Vonier, P.M., Guillette, L.J. Jr., & McLachlan, J.A. (1996). Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272, 1489-1492.
The Meeting concluded that interactions between pesticide residues, other dietary constituents, and environmental contaminants could occur. The results of such interactions depend on many factors, including the chemical and physical nature of the substances, the dose, and conditions of exposure. The outcome, which cannot be predicted reliably, may be enhanced, mitigated, or additive toxicity. The safety factors that are used for establishing ADIs should provide a sufficient margin of safety to account for potential synergism.
The Environmental Core Assessment Group could not convene with the Toxicological Core Assessment Group and the FAO Panel of Experts on Pesticide Residues in Food and the Environment at the present Meeting because of budgetary restrictions within the International Programme on Chemical Safety (IPCS). Consequently, the assessments of the environmental fate and ecotoxicity of the pesticides that were scheduled have been delayed until 1997.
The Meeting expressed its regret that the Environmental Core Assessment Group was unable to meet in 1996. Because of the importance of the environmental assessments as an integral component of the comprehensive assessment of pesticides, the Meeting recommended to IPCS that it make every effort to obtain the funds necessary for convening the Environmental Core Assessment Group with the JMPR in the future.
