WHO Library Cataloguing-in-Publication DataJoint FAO/WHO Expert Commit - PDF document

WHO Library Cataloguing-in-Publication DataJoint FAO/WHO Expert Committee on Food Additives. Meeting (70 : 2008: Geneva, Switzerland).Evaluation of certain veterinary drug residues in food : seventieth report of the Joint FAO/WHO ExpertCommittee on Food Additives.(WHO technical report series ; no. 954)1.Food contamination. 2.Drug residues - analysis. 3.Drug residues - toxicity. 4.Veterinary drugs - toxicity.5.Veterinary drugs - pharmacology. 6.Risk assessment. 7.Maximum allowable concentration - standards.8.No-observed-adverse-effect level. I.World Health Organization. II.Food and Agriculture Organizationof the United Nations. III.Title: Seventieth report of the Joint FAO/WHO Expert Committee on FoodAdditives. IV. Joint FAO/WHO Expert Committee on Food Additives. V.Series.ISBN 978 92 4 120954 0 (NLM classification: WA 712)ISSN 0512-3054© World Health Organization 2009All rights reserved. Publications of the World Health Organization can be obtained from WHO Press,World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264;fax: +41 22 791 4857; e-mail: bookorders@who.int). Requests for permission to reproduce or translate WHOpublications … whether for sale or for noncommercial distribution … should be addressed to WHO Press, at theabove address (fax: +41 22 791 4806; e-mail: permissions@who.intThe designations employed and the presentation of the material in this publication do not imply the expressionof any opinion whatsoever on the part of the World Health Organization concerning the legal status of anycountry, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.The mention of specific companies or of certain manufacturers products does not imply that they are endorsedor recommended by the World Health Organization in preference to others of a similar nature that are notmentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initialcapital letters.All reasonable precautions have been taken by the World Health Organization to verify the informationcontained in this publication. However, the published material is being distributed without warranty of any kind,either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader.In no event shall the World Health Organization be liable for damages arising from its use.This publication contains the collective views of an international group of experts and does not necessarilyrepresent the decisions or the policies of the World Health Organization.Typeset in IndiaPrinted in India Veterinary Medicine, University of São Paulo, São Paulo,Dr P. Reeves, Veterinary Medicines and Residues, AustralianPesticides and Veterinary Medicines Authority, Kingston, ACT,Dr P. Sanders, Laboratoire dÉtudes et de Recherches sur lesMédicaments Vétérinaires et les Désinfectants, AgenceFrançaise de Sécurité Sanitaire des Aliments, Fougères,FranceProfessor G.E. Swan, Faculty of Veterinary Science, University ofDr S. Barlow, Consultant, Brighton, East Sussex, England Temporary Adviser)Ir A. Bulder, Institute of Food Safety (RIKILT) … Wageningen UR,Wageningen, Netherlands Dr C.E. Cerniglia, Division of Microbiology, National Center forToxicological Research, Food and Drug Administration,Department of Health and Human Services, Jefferson, AR,USA (WHOTemporary Adviser)Dr P.L. Chamberlain, Covance Laboratories, Vienna, VA, USA(WHO Temporary Adviser)Foodborne Diseases, World Health Organization, Geneva,Switzerland (WHO Staff Member)Dr B. Dunham, Chair, Codex Committee on Residues ofVeterinary Drugs in Foods, Director, Center for VeterinaryTemporary AdviserDr D. Grant, Consultant, Ottawa, Ontario, Canada Temporary Adviser) Dr Dunham was invited but not able to attend the meeting. Monographs containing summaries of relevant data ations are available from WHO under the title:Toxicological evaluation of certain veterinary drug residues in food. WHOFood Additives Series, No. 61, in press.Specifications are issued separately by FAO under the title: FAO JECFA Monographs6, 2009, in press.MME ON CHEMICAL SAFETYThe preparatory work for toxicological evaluations of food additives and con-taminants by the Joint FAO/WHO Expert Committee on Food Additives (JECFA)is actively supported by certain of the Member States that contribute to the workof the International Programme on Chemical Safety (IPCS). of the United Nations Environment Programme, theInternational Labour Organization and the World Health Organization. One ofthe main objectives of the IPCS is to carry out and disseminate evaluations ofthe effects of chemicals on human health and the quality of the environment. Use of JECFA reports and evaluations by registration authoritiesMost of the evaluations and summaries contained in this publication arebased on unpublished proprietary data submitted to JECFA for use whengistration authority should not consider to granta registration based on an evaluation published herein unless it has first re-for such use from the owner of the data or any secondparty that has received permission from may help to identify critical data gaps early in the evaluation and potentiallylead to the generation of suitable data that will permit a successful evaluationThe concepts embodied in the paper were discussed by the Committee. TheCommittee endorsed the proposal in principle and generally agreed withthe concepts as presented. The Codations for the draft, while it emphasized the following general and specificsented are more important than detailed considerations of roles andpresented to direct when and how tween risk managers and risk assessors that may not be fully reflected inThe Committee further noted the need to coordinate and, wherever ap-propriate, reference similar and related efforts, to ensure a comprehen-Risk Assessment of Chemicals in Food, decisions of this and other jointexpert committees and the FAO guidance document on risk analysis (Evaluations by the Committee are baVeterinary Drugs as defined in the Assessments on the potential risk to human specified misuse scenarios, wouldsessment of chemicals than the assessment of residues of veterinarydrugs, and those issues that were cross-cutting should be identified anddeveloped with the respective experts from other bodies.tree approach and identifying the target 2.2The Committee considered the Committee for Medicinal Products forVeterinary Use (CVMP) document entitled Reflection Paper on the NewResidues of VMP [Veterinarydated 22 September 2008 and submitted to the JECFA Secretariat, providesthe sixty-sixth JECFA (Annex 1, reference The Committee acknowledged the comments provided in the reflection paperstory of the deit fits into JECFAs evaluation of residues of veterinary drugs, as reported bynumber of issues that are being addressed as part of the FAO/WHO jointAssessment of Chemicals in Food. The current Committee confirmed theutility of the EDI as a tool to ensure that intakes of residues resulting fromuse of veterinary drugs in accordance with Good Practices in the Use ofVeterinary Drugs and the recommended MRLs do not exceed the ADI. TheCommittee acknowledged that the use of the EDI is currently applicable onlyreflected by the ADI. The Committee reconfirmed that it requires an adequatedata set to estimate the EDI. When the data are not adequate to estimate theEDI, other conservative approaches to are applied. Future work will address considerations to identify the appro-priate measures of hazard, consumption toxicity and acute exposure, as might be appropriate for an ARfD. As notedby the sixty-sixth JECFA, the EDI should not be applied when there is concernfor acute toxicity or acute exposure. Fo2.3Residues of veterinary drugs in honey and possible approachesto derive MRLs for this commodityregarding honey from thesixty-sixth meeting of the Committee (Annex 1, reference sixth Committee recommended that a paper be prepared by an expertwith experience in beekeeping and hoto consider if a separate approach for case, to develop a draft recommendation for consideration at the next meeting.The fifty-second meeting of the Committee (Annex 1, reference comment on the matter; however, no formal comments were provided.Points to considerThe Committee noted that there were a number of factors to consider in de-veloping a process to the use of veterinary drugs and pesticides for bee health. They include, butmay not be limited to, the following points:The recommendations must be within the Committees terms of refer-ence, with adequate flexibility to meet differing conditions and avail-There is a need to accommodate a robust yet conservative approach tothat the Committee considers necessary for recommending MRLs.uct containing the active ingredient is currently registered by a nationalin most countries are considered as aactive sponsors to provide studproducts, breakfast cereals and baked goods, in addition to direct con-in intake estimates.Several substances used to manage bee health are unlikely to raise publichealth concerns, because intakes of residues resulting from effective useSome proprietary products are not therefore approved dosages and conditions of use do not exist.For a number of substances registered for use by national authorities, nocontemporary toxicological evaluation may have The Committee recognized that there are substantial production and trade inhoney; however, there are very limited numbers of residue (MRL) standardsfor residues in honey. Honey production figures for 2005 indicate that ap-proximately 1400 000 tonnes were produced worldwide. Honey productionis subject to numerous environmental factors, such as cropping, weatherconditions and the impact of pests and pathogens. that typically leave residues in edible beelipophilic acaricides (residues in wax and propolis).need to be considered in exposure es-timates. The ratio of honey to wax is typically 9:1.Substances with an existing ADI and/or MRL in a food-producing animalor food commodityThe main groups of substances that typically leave residues in edible beeproducts are antibiotics and persistent lipophilic acaricides. Of the productsknown to be used for treatment of bee national registration and a JECFA or JMPR evaluation with an ADI and/orMRL (or the equivalent in national legislation) for either a food-producingSubstances generally regarded as safeSeveral substances are unlikely to raise public health concerns, because anyuse in food-producing animals, especially the use in bees, is generally re-garded as safe. Examples of such substances include formic acid, lactic acid,the case of a substance that has clearin honey and that the ADI is sufficient so that no MRL would be required andthe ADI is not exceeded. In the case of a new substance not previously con-sidered for registration by national authorities, substances would have to beevaluated as new animal drugs or pesticides and subject to a full food safetyrisk assessment.Use of non-approved veterinary drugs or pesticidesIn the situation where a substananimals (e.g. chloramphenicol or nitrofurans), no Suggested tools for data generationWhere an established ADI exists for use in another species as either a vet-erinary medicine or pesticide, this would generally require a smaller set ofadditional data for honey, as an ADI exists.1.Design criteria for residue data studiesStudy design for residue determinations must take into account how theresidue behaves in honey, number of apiaries involved, repnumber of frames per hive sampled;number of samples of wax and honey from a frame;number and spacing of time points to describe the kinetics of formationand after the treatment until the end of the trial;scheme for the analysis of individuclimatic information for the duration of the trial, including season of thecrops on which bees forage;temperature profile within the hive;data on any supplemental feed given to bees;data on bee health and bee/parasite mortality during the study;The above factors recognize the unique nametabolites collect in the honey, and the only mechanisms for reduction areical or thermal degradation of the residues in the honey or through such factorsas pH and environmental conditions. Bees commonly mocan lead to significant variations in residueconcentration, even across the same frame in all three hive dimensions.