Residues of some veterinary drugs in animals and foods

147 Pages·1999·6.5 MB·English

by  Joint FAO WHO Expert Committee on Food Additives (DE-601)102322449 (DE-588)20291826

Residuesofsome
veterinarydrugs
inanimalsandfoods
Azaperone
Bovinesomatotropins
Chlortetracycline,oxytetracycline
andtetracycline
Dexamethasone
Diclazuril
Eprinomectin
Febantel,fenbendazoleandoxfendazole
Gentamicin
Imidocarb
Moxidectin
Nicarbazin
Procainebenzylpenicillin
Sarafloxacin
Spectinomycin
Residuesofsome FOODAFNAOD
NUTRITION
veterinarydrugs PAPER
in animalsandfoods 41/11
Monographspreparedbythe
fiftiethmeetingofthe
JointFAOA/VHOExpertCommittee
onFoodAdditives
Rome,17-26February1998
WORLD
HEALTH
ORGANIZATION
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ISBN92-S-1O420O-2
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©FAO1999
Copyrightedmaterial
Ill
TABLEOFCONTENTS
Page
ListofDarticiiiniils y
Ablircviationa is
Introduction xi
Monographs:
Azaperone I
Bovinesoinalolropins 3
ClilortelracYcline,owlelracvcliiieandleiracvcliiie 23
Dexanielltosone 23
Diclazuril 29
Eprinomectiii 31
Febantel.fenbendazoleandoxfeiidazole 49
Gemamicin fij
Imidocaife 65
Moxideclin 22
Nicaifaaain 83
ProcainebenzYlpenicillin 95
Sniiinoxacin 1C2
Speclinoiiivein 119
Annexes:
1.SumiraryofJECFAevaluationsofveterinafvdrugresiduesfromthe32***meetingto 133
tliepreseni
2.Reconiniendationsonliiecompounds 141
TH±e One
JOINTFAO/WHOEXPERTCOMAUTTEEONFOODADDITIVES
Rome,17-26February1998
Listofparticipants
Members
DrL.-E.Appelgren.ProfessorofPharmacology,FacultyofVeterinaryMedicine,SwedishUniversity
ofAgricultureSciences,Uppsala,Sweden
DrD,Arnold,DeputyDirector,FederalInstituteforHealthProtectionofConsumersandVeterinary
Medicine,Berlin,Germany
DrJ.Boisseau,Director,LaboratoryofVeterinaryDrugs,NationalCentreofVeterinaryandFood
Studies,Fougbres,France{Chairman)
oPfroMfedAi.cRi.neB,ooHbaims,meSrescmtiiotnhoCfaCmlpiunisc,alLoPnhdaormna,cUolKogy,DivisionofMedicine,ImperialCollegeSchool
SDarfeRt.yaElnldis,InDsipreeccttioorn,SeSrciveinctei,fiDcepReasretamrecnhtaonfdAgOrviecruslitguhrte,,OWfafsihciengotfoPnu,blDiCc,HUeaSlAth(aJonidntScRiaepnpcoer,teFuoro)d
DrR.C.Livingston,CenterforVeterinaryMedicine,FoodandDrugAdministration,Rockville,MD,
USA
DrJ.D.MacNeil,Head,CenterforVeterinaryDrugResidues,HealthofAnimalsLaboratory,
CanadianFoodInspectionAgency,Saskatoon,Saskatchewan,Canada
ProfJ.G.McLean,NelsonRoad,SouthMelbourne,Victoria,Australia(Vice-Chairman)
CDerntMe.rA,forMilVleetre,riDneapruytyMeDdiirceictnoer,foFrooHdumaanndFDoomdgSaAfdemtiyn,isOtfrfaitcieoon,fNReocwkvAinlliem,alMDDm,gUESvaAlua(tJiooinn,t
Rapporteur)
ProfE.S.Mitema,Chairman,DepartmentofPublicHealth,PharmacologyandToxicology,College
ofAgricultureandVeterinarySciences,UniversityofNairobi.Kabete,Kenya
ProfJ.Palermo-Neto,DepartmentofPathology,FacultyofVeterinaryMedicineandTechnologyof
AnimalHusbandry.UniversityofSaoPaolo.SaoPaolo,Brazil
DrA.Pintdr,DeputyDirectorGeneral,NationalInstituteofHygiene,Budapest,Hungary
DrJ,L.RojasMartinez,Chief,ToxicologyandResidueSection,NationalLaboratoryofVeterinary
Sciences,MinistryofAgriculmreandAnimalHusbandry,SanJos6.CostaRica
DrP,Sinhaseni.DeputyDirectorforResearch,InstituteofHealthResearch,Chulalongkora
University.Bangkok,Thailand
DrS.Soback,Head.NationalResidueLaboratory,KimronVeterinaryInstitute.Ministryof
Agriculture,BeitDagan,Israel
DrR.Wells,ScienceConsultant,MertiwaStreet,Gordon,NewSouthWales,Australia
Secretariat
FDoroCd.Ea.ndCDerrauigglAidam,inDiisrtercatotri.onD,iJveifsfieornsoonf,MAiRc.roUbiSoAlog(yW,HNOatTieonmaplorCaernyteArdvfiosrerT)oxicologicalResearch.
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vi
DrP.Chamberlain,Toxicologist,DivisionofHumanFoodSafety,OfficeofNewAnimalDrug
Evaluation,CenterforVeterinaryMedicine,FoodandDrugAdministration,Rockville,MD,USA
(WHOTemporaryAdviser)
DrS.D.Chemausek,Endocrinologist,Children’sHospitalMedicalCenter,Cincinnati,OH,USA
(WHOTemporaryAdviser)
DRerseRa.rFcuhcahns,dOHcecaudp,atDieopnaarltHmeeanlttho,fZEaxgpreerbi,meCnrtoaaltiTaox(iWcHolOogTyemapnodrEacroytoAxdviicsoelro)gy,InstituteforMedical
DrL.Good,VeterinaryMedicineDirectorate,Addlestone,Surrey,UK(WHOTemporaryAdviser)
DrM.K.Hansen,ConsumerPolicyInstitute,ConsumerUnion,Yonkers,USA(WHOTemporary
Adviser)
Dr.R.J.Heitzman,ScienceConsultant,Newbury,Berkshire,England(FAOConsultant)
CDrh.emJi.cLa.lHSaefrertmya,nW,HSOci,entGiesnt,evaA,ssSewsistmzeenrtlaonfd(RiWsHkOanJodinMtetSehcordeotlaorgyi)es,InternationalProgrammeon
Mrs.E.Heseltine,CommunicationConsultant,Saint-Lion-sur-V6z4re,France(WHOTemporary
Adviser)
Dr.K.Mitsumori,Chief,ThirdSection,DivisionofPathology,BiologicalSafetyResearchCenter,
NationalInstituteofHygienicSciences,Tokyo,Japan(WHOTenyporaryAdviser)
DPirsoefasCe.s,E.KaNroorldi,nskCahaIinrstmianint,et,DeHpuadrdtimnegnetUonfivIermsmiutnyolHoosgpyi,talM,icHruodbdiionlgoeg,y,SwPaetdheonlo(gyWHaOndTeInmfpeocrtiaoruys
Adviser)
aDnrdPF.ooOdlsAednm,inHiesatdr,atiPoant,hoSlaobgoyrgS,ectDieonnm,aIrnksti(niWteHOforTeFmopoodraSrayfeAtdyviasnedr)Toxicology,DanishVeterinary
DrJ.Paakkanen,NutritionOfficer,FoodQualityLiaisonGroup,FoodQualityandStandards
Service,FoodandNutritionDivision,FAO,Rome,Italy(FAOJointSecretary)
aMnrdsEMn.vEi.rJo.nmPernotnakl,PrCoetnetcetironf,orBiSlutbhsotvaennc,esThaendNeRtihsekrlAasnsdess(smWeHntO,TNeamtpioornaalryInAsdtviitsuteer)ofPublicHealth
GDurelLp.hR,itGtuere,lpEhx,ecOunttiavreioD,irCeacntoard,aC(aWnaHdOiaTneNmeptowroarrkyAodfvTiosxeri)cologyCentres,Universityof
DrG.Roberts,Head,ChemicalProductsAssessmentSection,TherapeuticGoodsAdministration,
CommonwealthDepartmentofHealthandFanulyServices,Canberra,ACT,Australia(WHO
TemporaryAdviser)
DrB,Roestel,LaboratoryofVeterinaryDrugs,NationalCentreofVeterinaryandFood Studies,
Fougires,France(FAOConsultant)
DHrumRa.nC.SeSrivlilcs,es,HeRaeds,eaMroclheTcruilaanrglPeatPhaorlko,gyN,C,NaUtiSoAnal(WInHsOtimTteempoofrHaerayltAhd,viDseerp)artmentofHealthand
DMrD,S.USSunAdl(ofW,HODirTeecmtopro,raCreyntAedrvifsoerr)VeterinaryMedicine,FoodandDrugAdministration,Rockville,
PMerdoifcFi.nRe.,UUnnigveermsaicthy,ofInLsetiiptzuiteg,ofLeiPphzairgm,acGoelromgayn,yPh(aWrHmaOcTyemapndorTaorxyiAcdovliosgeyr,)FacultyofVeterinary
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VII
DrN.E.Weber,Leader,ResidueChemistryTeam,OfficeofNewAnimalDrugEvaluation,Center
forVeterinaryMedicine,FoodandDrugAdministration,Rockville,MD,USA{FAOConsultant)
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ABBREVIATIONSUSEDINTHISDOCUMENT
AADUIC --aarcecaeputnadbleerdcaoinlcyenilnrtaatkieon- pmmg -•mmiilclriogmreatmer
Timccurve min -minute
bbABBB.wvqPSi...Td.BW -•••-•BtbaBbrwoveoiivecdtcirqyieanusgwheeaerePsdeiohiagmahya(rttomonatecrodoippsoiiennit/asec) mMMMnMlSRRRorLTNo -•-•-•mmmmnmiaaeulasrlamxisknblieiesmtrrrrpueeersmecistdrireedonsumcieeedtutreiymleimit
’’C -degreesCctcius na -notanalyzed,assayedor
C‘*AcP -•-rcmahadlixooirlamambupcmlhlecenodincCcoealnrtbroantion nNdE.RND --annvooatnildeaexbttlerecatcetdableresidues
TcCmi* ••cmuibcircoccuerniteim(ertadeiroactivity) nngm,NM ••nnoatnmoegarsaumred,if
ceCorVnee ••-ccchoolncocmrectnietterrnaatlciyoocfnlivnaeriation nNmMR •-annpuapcnlloiemcaeartbelmrea,gnieftaipcplicable
dDEPCMD,dpm -•-dedilaseyicnttreognractaipotnurpeerdemtiencuttore ONTOCEL -•rnoeoxs-ytoocbntsarcnarccveyecdl-ienfcfectlevel
eEgL.ISA -•feonryezxmaempllabeelledimmunoassay ppppbm -•ppaarrttssppeerrbmiilllliioonn
eEqPorEQ ‘-EequuriovpaelaenntsPharmacopoeia rRIA •-rreagdrieosismiomnuncooaefsfstacyient
FFDA -•fFeomoadleandDrug SRASD ••rSepleactiifviecsAtcatnidvaint)ydeviation
gPGgC ---Aggmdarimsacimrcnohigsrtroramamattioognraphy sSSs.iDEcc.M -•--scssotturaabrnncedducaattrralddynedesoerpuvresiolarlteoidfonmean
GGClLLPC •-•ggcGaahossrol-orldomiiqaLnutaiioebdagotrriaantpaolhryyPractice Ts.Ct.do.r ----lholaienlmtcferealfiacofyerdcaUmnyaeximum
Gh’HHVPPLC ----CthhGrhiooigruothroidumpmaVetertofegorrrimanapanhrcyyePlriaqcutiidce TTTTTRSLRMDCAS ---••tttitioorlittiiiaamnellerlimrrahiaeyyodsleniisriodicauclceyhstslprievodciemitrafyiitvcoagtriavephy
iii...eim.n..,i.IM ---tmilnltiartraaUmmuussccuullaarrinjection UUSDDA '--duUenStcehcDtaeinpoganerdtmdernutgof
ii..vp..,,IIPV --itnntirraapveerniotuosneal USP -AUgnriitceudltSutralees
<k1g --rkaitleocgornasmtant UV •Pulhtarramviaocloetpeia
MLLLLLMSCOOoCrDQ1 ----•--lcllllmmiiiioioatmmqqurlliiuuenttaeiitddrooiffncsocghrdqiruenmoattoinemltlcalitetatitoaoitgnoirnoanphy VvwwW%></t/dTvv ••---'--lgpwwwvvereiecoosertiillsaghguuctUhdhemmeitrlnreeaa/t/nwtovvhafooallldnutiumsimetmereibution
max -maximum £ -equalorlessthan
m/m •nuss/mass -equalorgreaterthan
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INTRODUCTION
Tprheepamroendobgyratphhesfoifntietthhemreeestiidnuegsooff,thoerJsotinattemFeAntOs/oWnH,OtheExpIeSrtcoCmopmomuintdtseecoonntaFinoeoddiAnddtihitsivveosl(uJmEeCFwAe)r,e
whichwasheldinRome,17-26February1998.JECFAhasevaluatedveterinarydrugsatpreviousmeetings,
includingthe12th'.26lh^27th\32nd^34th^36th*.38th’,40th‘.42nd’.43rd'®.45th",47th'^and48th‘’
meetings.
implicatiIonnsrfeosrpohnusmeantoheaaltghroawnidnigntecronnacteironnalabtroaudte,maasJsoi-nmtedFiAcaOtiAoVnHoOfEfxopoedrtpCroondsuuclitnagtioanniomnalRsesiadnudestohef
VeterinaryDrugswasconvenedinRome,inNovember1934‘*.Amongthemainrecommendationsofthis
consultationweretheestablishmentofaspecializedCodexCommitteeonResiduesofVeterinaryDrugsin
FtNoooovthdeismsb(CeCormCmR1iV9t8Dt6Fe,e)taahnneddntteohwelthype-ecrmrieeoadmitbceedcroCcnCovueRnntVirnDigeFsoofrfeaanFfAfaipOrpmraeondpdritWahteHeOnbe.oeddAytftooirtspsrfuoicrvshitdseaesissnciidoeennpteiinfnidWceanbstohsdicyniegntatonifndicDm.aaCddv.eiciaen
numberofrecommendationsandsuggestionstobeconsideredbyJECFA'*. In responsetothese
recommendations,thethirty-secondJECFAmeetingwasentirelydevotedtotheevaluationofresiduesof
veterinarydrugsinfoods.Subsequently,the34lh.36th,38th,40th,42nd,43rd,45th,47th,48thand50th
meetingsofJECFAwerealsodedicatedexclusivelytoevaluationofveterinarydrugs.
TprhieontteyntlhisstesosfivoentoerfitnhaeryCdCrRuVgsDFre,quhierlidnginevSaalnuaJtoisoen,.CTohsetadrRuicgas,edvuarluiantgedOcdtuorbienrg-tNhoeve50mlbherme1e9t9i6n,groefviJsEedCFthAe
includedthesecompounds,exceptcyhalothrin,oiaquindoxandporcinesomatotropin,(heevaluationofwhich
waspostponedtoafuturemeetingoftheExpertCommittee.
Hiepresentvolumecontainsmonographsoftheresiduedataon16oftheIScompoundsontheagenda.For
(hetwocompounds,azaperoneanddiclazuril,submittedforatoxicologicalre-evaluation,onlyastatementof
confirmationoftheexistingmaximumresiduelimitswasmade.
Theanthelminthicagents,febanlel,fenbendazole,oxfendazoleandmoxidectinhadbeenconsideredbeforeby
theCommittee.Eprinomectin,ananthelminthicagent,hadnotbeenevaluatedbefore.
Fiveofthesevenantimicrobialagents,chlortetracycline,oxytetracyciine,tetracycline,gentamicin,and
spectinomycinhadpreviouslybeenevaluatedbytheCommittee. Theremainingantimicrobialagents,
procainebenzylpenicillinandsarafloxacinhadnotbeenevaluatedbefore.
Ofthethreeantiprotozoalagents,diclazurilhadbeenpreviouslyevaluatedbytheCommittee. Imidocarband
nicarbazinwerebeforetheCommitteeforthefirsttime.
Theremainingthreecompounds,dexamethasone.aglucocorticosteroid,bovinesomatotropin,aproduction
aid,andazaperone,atranquilisingagent,hadbeenevaluatedpreviouslybytheCommittee.
ThepertinentinformationineachmonographwasdiscussedandappraisedbytheentireCommittee.The
monographsarepresentedinauniformformatcoveringidentity,residuesinfoodand(heirevaluation,
metabolismstudies,tissueresiduedepletionstudies,methodsofresidueanalysisandafinalappraisalofthe
smtoundoygrraepsuhltsi.sbMasoerde.ArecseuntmmpaurbylicoaftitohnesJaEnCdFAdoecvuamleunattisonasrefrroemfetrheenc3ed2,nditnocltuhdeinpgrestehnotse50otnhwmheeitcihngthies
includedinAnnex1.
TheassistanceoftheexpertsandFAOconsultantinpreparingthesemonographsisgrateftillyacknowledged.
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