Committee on the Carcinogenicity of Chemicals in Food, Consumer Products and the Environment

16 Pages·2008·2.04 MB·English

Committee on the Carcinogenicity of
Chemicals in Food, Consumer Products and
the Environment
177
AnnualReport2007
Preface
TheCommitteeonCarcinogenicityofChemicalsinFood,ConsumerProductsandthe
Environment(COC)evaluateschemicalsfortheirhumancarcinogenicpotentialatthe
requestofUKGovernmentDepartmentsandAgencies.Themembershipofthe
committee,agendasandminutesofmeetings,andstatementsareallpublishedonthe
internet(http://www.advisorybodies.doh.gov.uk/coc/index.htm).
During2007,theCommitteeprovidedadviceonarangeofinterestingtopics.Itcarried
outanumberofreviewsandgavefurtherconsiderationtotheissueoffolicacid
fortificationandcarcinogenesis.
Amongthegenericissuesconsideredbythecommittee,itgavefurtherconsiderationtotheissueofrisk
communication.Inthiscontext,itassessedtheuseoftheMarginofExposure(MOE)approach,whichis
beingdevelopedininternationalforaforriskcommunicationandriskprioritisationofnon-threshold
carcinogens.AttherequestoftheHealthandSafetyExecutive,thecommitteeprovidedtechnicalguidance
onthedraftguidanceforassessmentofthecarcinogenicityofchemicalsinthecontextofnewEuropean
legislationontheRegistration,Evaluation,AuthorisationandRestrictionofChemicals(REACH).
ChairingtheCOCcontinuestobeachallengingbutrewardingtask.Ithankthemembersandsecretariatfor
theirsupportduringthepastyearandlookforwardtoworkingwiththemonthechallengesahead.
ProfessorDavidHPhillips
BAPhDDScFRCPath
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Assessing the risks of acute or short-term exposure to carcinogens
3.1 TheDepartmentofHealthandtheHealthProtectionAgencyareoccasionallyaskedtoprovideadvice
onthehealthrisksofacuteorshort-termexposuretogenotoxiccarcinogens.In2006,theysought
theadviceoftheCOConhowthismightbedoneand,afterdiscussion,membersdecidedthatit
wouldnotbeappropriatetouseanacuteT25approach.OnememberhadalsoinformedtheCOC
thatthereweresomepapersintheliteraturewhichmightindicateawayforwardandthreeofthese
werediscussedbythecommitteeatameetingin2007.
3.2 Anunderlyingprincipleintheapproachessuggestedbytwoofthepaperswasthattumourincidence
islinearlyrelatedtothecumulativedoseofachemical.However,theCOCdisagreedwiththis
principle,whichitassumedhadderivedfromobservationsabouttherelationshipbetweenradiation
doseandcancerrisk.Inthecaseofchemicals,itwasnotedthatDNArepairprocessescouldbe
significantatlowdoses,anon-linearresponsecouldoccurduetothecomplexityofthecarcinogenic
process,andgenotoxiccarcinogensmayhavedifferenteffectsegathighdosessomegenotoxic
carcinogenscouldalsopromotecancerviaacytotoxicmechanism.Therelationshipcouldalsobe
affectedbylatency. Itwasnotedthattherewerefewrelevantepidemiologicaldataonchemicalsbut
itappearedthat,forsmoking,theriskwassublinearwithtime,atleastforlungandbladdercancer.
3.3 Onepaperhadconsideredwhetherexposureof1-10daystogenotoxiccarcinogensmaycontributeto
tumourdevelopmentand,ifso,whetherthiscontributiontocancerriskcouldbequantified.A
pragmaticapproachwasproposed,whichusedthepremisethattumourincidenceislinearlyrelatedto
thecumulativedoseofachemicalandincorporatedtheprincipleoftheVirtuallySafeDose(VSD)
associatedwithan"acceptable"risklevel.Theapproachthenappliedfactorstoscaleupfromlowlevel
exposuredailyover70yearstothedosewhichmightbeacceptableifexposurewasonlyfor1day,or
2-10days.TheCOCnotedthatthepaperwasmainlytheoreticalandusedmathematicalmodellingto
developriskestimatesfromanimalcarcinogenicitydata(anapproachthatisnotrecommendedbythe
COC).Althoughtherewereareasofuncertaintyandanumberofassumptionsintheproposed
approach,membersconsideredthatextrapolationfromlifetimeexposurestoshort-term(upto10
days)exposuresforlowdoseswouldprobablyoverestimatethecancerrisk.Theyconsideredthat,
althoughtherewasanassumptionthatcertainsubpopulationswouldbemoresusceptiblethanothers,
therewasnosuitabledatatoallowanyquantitativeestimationandassociatedadjustmenttocancer
riskestimates.However,itwassuggestedthatitmaybepossibletoadaptthemethodbyusingthe
MarginofExposure(MOE)approachandthatthismightprovideapragmaticapproachtotherisk
assessmentofshort-termexposurestogenotoxiccarcinogens,althoughtherewouldbesome
associateddegreeofuncertainty.
Betel quid, Pan Masala and areca nut
3.4 Thisitemwasconsideredin2006butnotincludedinthe2006AnnualReport.
3.5 Arecanutisaningredientofbetelquidorpanmasala,whichischewedasanaidtodigestionandasa
stimulant.Italsomayhavelimiteduseasafoodingredient.TheCOClastconsideredthe
carcinogenicityofarecanutin1994butsincethen,anumberofrelevantnewpapershadbeen
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AnnualReport2007
published.Consequently,theFSAsoughttheviewoftheCOCastowhetherthenewinformationwas
sufficienttowarrantupdatingitspreviousadvice,andwhetheranyconclusionscouldbedrawnabout
theuseofarecanutasafoodingredient.
3.6 InthepreviousCOCassessment,theCommitteehadconsideredarangeofdataandhadconcluded
thefollowing:
(cid:1) Therewasevidenceofmutagenicandcarcinogenicactivityofarecanutextractsandderived
compoundsinexperimentalsystems.Inparticular,thepotentcarcinogenicactivityoftheareca-
derivednitrosamine,3-(methylnitrosoamino)-propionitrile(MNPN),hadbeenconfirmedand
methylandcyanoethyladductshadbeendetectedintheDNAofthetargettissuesinwhichthe
tumoursdeveloped.Therewasevidencethatendogenousnitrosationofarecanutalkaloidscan
occurinanimalsandhumans;andarecanutderivednitrosamines,includingMNPN,havebeen
detectedinthesalivaofbetelquidchewers.
(cid:1) Therewereverylimiteddatafromepidemiologicalstudiesontheeffectofbetelorarecanut
productswithouttobacco,whichdidnotallowanyconclusiontobedrawn.Therewas,however,
sufficientepidemiologicalevidenceofalinkbetweenthechewingofbetelquidcontaining
tobaccoandcancerinhumans.
(cid:1) Useoftheseproductswithouttobaccowaspossiblycarcinogenicinhumans.
3.7 In2003,theInternationalAgencyforResearchonCancer(IARC)assessedtheuseofbetelquid,and
concludedthatboththechewingofbetelquidandarecanutshouldbecategorisedasGroup1
carcinogens(carcinogenictohumans).Initsconclusions,IARCstatedthatthereissufficientevidence
inhumanstoconcludethatbetelquidchewedwithouttobaccocausesoralcancer.IARCalso
concludedthattherewassufficientevidenceinanimalstoconfirmthecarcinogenicityofbetelquid
andarecanutwithouttobacco. ThisfollowedapreviousIARCreviewin1985,whichconcludedthat
therewasinadequateevidenceforthecarcinogenicityofbetelquidchewedwithouttobacco.
3.8 TheCOCreviewedanumberofepidemiologystudiespublishedsince1993andnewanimalstudies
whichattemptedtoidentifymechanismsforthecarcinogenicpotentialofarecanutextractsand
agreedwiththeIARC(2003)conclusions.Thecommitteeconsideredthatmostoftheevidence
suggestedthatarecanutisasiteofcontactcarcinogenactingbyagenotoxicmechanism,andnoted
thattherewassomeevidencethatanon-genotoxicoxidationmechanismcouldalsobeinvolved. The
carcinogenicmechanismwaslikelytoinvolvethenitrosationofprecursorchemicalspresentinareca
nut. Itwasnotclearwhythereappearedtobeanincreasedsite-of-contactcancerriskforthosewho
swallowedthejuice.TheCOCalsoconsideredthattherewasnoclearevidencethattheuseofareca
nutwithouttobaccocausedprimarylivercancerorothercancersatdistantsites.
3.9 TheCOCconcludedthattherewasnowsufficientevidenceforacausallinkbetweenthechewingof
arecanutwithouttobaccoandoralcancerandthat,overall,arecanutshouldberegardedas
carcinogenictohumans.Membersalsoagreedthattheuseofarecanutasafoodingredientwas
potentiallycarcinogenic.
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Folic acid fortification and carcinogenesis
3.10 In2005,theScientificAdvisoryCommitteeonNutrition(SACN)askedforadvicefromtheCOCon
whetherdietaryfolicacidintakeisassociatedwithincreasedcancerrisk.Afterreviewingtheavailable
data,theCOCrecommendedaprecautionaryapproachinconsideringmandatoryfortificationofflour
withfolicacid.Subsequently,SACNhadaskedforfurtherclarificationofthisadviceandtheChairman
hadagreedthataimingtoincreaselowlevelintakeswhilstensuringthathighlevelintakesdonot
increaseisconsistentwithaprecautionaryapproach.Asaresult,theSACNconcludedthatmandatory
fortificationshouldonlybeintroducedifitisaccompaniedbyactiontoreducefolicacidintakesfrom
voluntarilyfortifiedfoodstoensurethatthenumbersofpeoplewithintakesabovetheEVM’supper
intakeleveldonotexceedcurrentlevelsandthereisnosubstantialincreaseinmeanintakesorinthe
folatestatusoftheUKpopulation.
3.11 AtitsJuly2007meeting,theCOCdiscussedfurtherrecentpublicationsonfolicacid,includingtwo
editorialsfromtheBritishMedicalJournal.Anabstractofarandomisedclinicaltrialwithfolicacid
supplementsforthepreventionofcolorectaladenomashadbeenseenbythecommitteewhenit
consideredthistopiclastyear;thefullpaperhadnowbeenpublished.Thishadfailedtoshowany
evidencethatfolicacidsupplementationprotectsagainstcolorectalcancerbutthattherewasan
excessofprostatecancercasesinthefolicacidgroupcomparedtocontrols. Itwassuggestedthat
thismightbeduetopromotionofpre-neoplasticlesionstoneoplasms. Memberswereremindedthat
thestudyhadnotbeendesignedtoinvestigatetheeffectoffolicacidsupplementationonprostate
cancerriskandthattheauthorsofthestudyhadthemselvescommentedthatthiscouldbea
spuriousassociation.ItwasalsonotedthattheremayhavebeenadifferentialrateofPSAtesting
betweenthetwogroups,andthatmandatoryfortificationoffoodwithfolicacidhadbeen
introducedintheUSwhilethisstudywasinprogressandtotalintakeoffolicacidwouldhave
exceededtheguidancelevelforupperintakeof1mg/dayrecommendedintheUKbytheExpert
GrouponVitaminsandMinerals(EVM).AccordingtotheSACNreport,therewasnoclearchangein
theincidenceofprostatecancerfollowingmandatoryfortificationintheUS. Asecondpaper
reportedastudyondietaryintakeoffolateandco-factorsinfolatemetabolism.
3.12 Thecommitteeconcludedthat,onbalance,itwascontentwiththeproposalsbytheFSABoardto
recommendtoUKhealthministersthatthereshouldbemandatoryfortificationofafoodwithfolic
acid,withcontrolsonvoluntaryfortificationandguidanceonuseofsupplements,monitoringofthe
folicacidintakesandstatusoftheUKpopulationandpostulatedrisks–includingcancerincidence-
andareviewofthedataonthebenefitsandpossiblerisks5yearsafterintroductionofmandatory
fortification. Membersaskedtobeinformedoftheoutcomeofthe5yearreview.
3.13 Followingthemeeting,MemberswereinformedthattheChiefMedicalOfficerhaddecidedto
conveneaspecialsubgroupoftheScientificAdvisoryCommitteeonNutrition(SACN)toexamine
furthertwopapersonthepotentialadverseeffectsoffolicacidontheriskofcolorectalcancerand
thattheChairmanhadbeeninvitedtoparticipateinthissubgroup.
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AnnualReport2007
Formaldehyde
3.14 Atthe2006horizonscanningexercise,thecommitteewasinformedthattheInternationalAgencyfor
ResearchonCancer(IARC)hadconcludedthatthereis“strongbutnotsufficientevidenceforacausal
associationbetweenleukaemiaandoccupationalexposuretoformaldehyde”.Thisconclusionwas
temperedbecauseitwasnotpossibletoidentifyamechanismforleukaemiainduction.Aliterature
paperhadarguedagainsttherebeingacausalrelationshipforformaldehydeandleukaemiariskonthe
groundsthatthereisnoevidencetosuggestthatformaldehydereachesanytargetorganbeyondthe
siteofcontact,noindicationthatformaldehydeistoxictothebonemarrow,andnocredible
evidencethatformaldehydeinducesleukaemiainexperimentalanimals.In2007,itconsideredthe
conclusionsofarecentCOMreviewofformaldehydeandtheextractfromtherecentIARC
monographonformaldehydewhichsummarisestheepidemiologicalfindingsonleukaemia.
3.15 TheCOMadviceisgiveninparagraph2.17ofthisdocument.TheCOCnoteditsconclusionsand
consideredakeypointtobethatinhalationexposuretoexogenousformaldehydewouldhaveno
effectontheendogenousconcentrationofformaldehyde.MembersthereforequestionedhowIARC
hadconcludedthattherewasacausalassociationbetweenleukaemiaandoccupationalexposureto
formaldehyde,particularlyinviewofthemetabolicdataintheIARCsummary.TheCommittee
decidedthatitdidnotwishtoreviewtheepidemiologicalevidenceindetail.
Quantitative structure-activity relationships (QSAR)
3.16 TheCOCconsideredtworecentlypublishedpapersontheuseofQSARtopredictcarcinogenicity.
Onepaper,fromtheUSFoodandDrugAdministration(FDA)describedanevaluationofthe
performanceofaparticularsoftware,MDL-QSARpredictivediscrimantanalysismodellingofrodent
carcinogenicity,toestimatethecarcinogenicpotentialofsmall,organic,naturallyoccurringchemicals
foundinthehumandiet.Thepredictiveperformanceforthisgroupofchemicalsandacontrolgroup
of19knownsyntheicdietaryconstitutentswas97%sensitivityand53%specificity.Thesecondpaper,
byBenignietal(2007),describedanddiscussedpreliminaryfindingsfromaprojecton(Q)SARsfor
mutagenicityandcarcinogenicityinitiatedbytheEuropeanChemicalsBureauandcarriedoutbythe
IstitutoSuperiorediSanita’,inthecontextoftheforthcomingREACHlegislation.
3.17 MembersconsideredthatitwouldbeusefultoreviewthefinalresultsoftheREACHprojectwhen
thishadbeenpublishedandthentodecidewhethertoundertakeafullreviewofQSARfor
predictionofcarcinogenicity.
Risk communication
3.18 In2005,theCOCandCOMdecidedthattheyshouldcollaboratetoimprovethewayinwhichthe
adviceonthepotentialcarcinogenicityandmutagenicityofchemicalsispresentedtothegeneral
public.In2006and2007,theCOCdiscussedthewaysinwhichthecarcinogenicriskofchemicals
mightbebettercommunicatedandputintocontextalongsideotherrisks. Membersnotedthatthe
primaryroleoftheCOCandCOMwastoprovideadvicetogovernmentdepartmentsandregulatory
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agencieswhichwereresponsibleforriskmanagementandriskcommunication.However,itwasagreed
thatawiderunderstandingofthelowrisksassociatedwithexposuretoenvironmentalcarcinogens
wasdesirable.
3.19 Onesuggestionwasthattherisksofenvironmentalcarcinogenesiscouldbecomparedwithother
involuntaryrisks,usingestablishedriskscalessuchastheCalmanriskscaleorthe“RiskIt”game
developedbytheHPAforradiation.However,thecommitteeconsideredthatitwouldnotbe
possibletodevelopsuchanapproachforchemicalsasselectionofexposurescenarioswouldbevery
difficult. Itsuggestedthatamoresuitableapproachmightbetocomparecloselyconnectedriskse.g.
thoseofnaturaltoxinsandsyntheticpesticideresiduesinoronthesamefoodstuff.TheCOCalso
agreedthatcurrentapproachestodraftingstatementsneededtobeimproved,withmoreinformation
onthereasonsforundertakingreviewsandnonexecutivesummariesdevelopedforallstatements. It
askedthesecretariattoconsidercarefullytheaudienceinanyfurtherpaperfortheCOC.
3.20 Aspartofthisitem,theFSAaskedtheCOCtocommentonthepotentialusefulnessoftheMarginof
Exposure(MOE)approachbeingdevelopedbytheEuropeanFoodSafetyAgency(EFSA),theWorld
HealthOrganisation(WHO)andtheInternationalLifeSciencesInstitute(ILSI)asawayofprioritisingthe
risksassociatedwithunavoidableexposuretogenotoxicchemicalcarcinogensinfood.TheMOEisthe
numericalvalueobtainedbydividingareferencepointonthedoseresponsecurveforcarcinogenicityin
experimentalanimalsbyestimatedhumanexposuretothechemical. Thepreferredreferencepointof
theaboveorganisationsisthelowerlimitoftheconfidenceintervalonthebenchmarkdose(BMD),
althoughtheyhavenotedthattheT25couldbeusedincaseswherethedose-responsedatawerenot
adequatetodefinetheBMDorthelowerlimitofitsconfidenceintervalofthe(BMDL).
3.21 TheCOCagreedthattheuseoftheMOEtoprioritisetheriskofexposuretogenotoxiccarcinogenswas
consistentwiththemostrecentCOCguidelinesandwouldalsocontributetointernational
harmonisationinthisarea.ItdiscussedtherelativemeritsofusingtheBMDL10orT25andnotedthatthe
BMDL10takesthequalityofthedataintoconsideration,duetotheuseofconfidenceintervals,whilst
theT25doesnot.TheT25wasusuallyderivedfrompoorerdatasets.Overall,itwouldbenecessaryto
decidewhichtouseonacase-by-casebasisdependingonthequalityoftheavailabledata.
3.22 AsystemforbandingMOEvalueswasagreedandisgivenbelowinTable1.Thisexpandsonproposalsfor
theinterpretationofthemagnitudeoftheMOEthathadbeenmadebyJECFAandEFSA,wherethere
wasaconsensusthatanMOEgreaterthan10,000indicatedlowconcern. Itwashopedthatthebanding
systemmightimprovethecommunicationofadviceongenotoxiccarcinogenstowideraudiences.
Table1:BandingofMOEvaluesforriskcommunication
MOEBand Interpretation
<10,000 Maybeaconcern
10,000-1,000,000 Unlikelytobeaconcern
>1,000,000 Highlyunlikelytobeaconcern
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3.23 HavingagreedtheMOEapproachinprincipleforthecommunicationandprioritisationofrisks,the
committeeconsideredindetailthemethodologyusedtoderivetheBMDL10.Itreviewedan
illustrativeexercisefor3genotoxicsoilcontaminants(hexavalentchromium,benzo(a)pyreneand1,2-
dichloroethane)andadvisedonseveralaspectsofthemethodologywhichshouldbeused. Members
involvedintheinternationalforarecommendedthattheCOCshouldreviewongoingworkonmodel
averagingwhenpublished.
Technical guidance for derivation of DNELs and risk characterisation of
non-threshold effects in the context of REACH
3.24 AttheMarch2007meeting,theHSEmadeashortpresentationtoinformmembersaboutprogresswiththe
developmentoftechnicalguidancefortheriskassessmentofsubstancesunderREACH(Registration,Evaluation,
AuthorisationandRestrictionofChemicals-anewEuropeanRegulation). Thisfocusedontheproposedguidance
fordealingwith"non-threshold"genotoxiccarcinogens.Twoapproacheswereproposed:oneisbasedonlinear
extrapolationfromanimalbioassaydatatoapredeterminedlowlevelofriskandtheotherisbasedonapplicationof
alargeuncertaintyfactor(UF)toasuitablereferencepointonthedose-responseforcarcinogenicity. Thelatter
approachwasincludedbecausetheUK,unlikemostotherEUmemberstates,doesnotusethelinearextrapolation
approach.BothapproachesgenerateaDerivedMinimumEffectLevel(DMEL)whichisdefinedasthelevelof
exposureabovewhichhumansshouldnotbeexposed. Memberswereinformedthatboththepredeterminedlow
levelofriskandtheuncertaintyfactorsweredecidedatpolicylevelandwerenon-negotiable.
3.25 TheCOCconsideredthattheUFandDMELmethodsareessentiallyequivalentbutdifferwithrespect
toriskcommunication.MembersnotedthattheUFapproachdifferedfromtheMOEapproachin
that,intheREACHmethodology,apredeterminedUFof10,000wastobeused.Memberswere
concernedaboutthederivationofanUFof10for'thenatureofthecarcinogenicprocess'giventhe
limitationsofcurrentknowledgeaboutDNArepair.
3.26 TherewasdiscussionoftheunitschosenfortheDMELvalueswithsomemembersfavouringtheuse
ofmoles/micromolesratherthandose/weight/day,becausethebiologicalresponseisbasedonthe
interactionofmoleculesofachemical,nottheweightadministered.However,itwaspointedoutthat
thiscouldbedifficultsincethepurityoftheactiveingredientisnotalwaysknownanditwouldbe
difficulttoassesssubstances,asopposedtosinglechemicals,onamolarbasis.Thecommitteealso
discussedtheproposalthat"biologicalcriteria"shouldbeusedtoassesstherelevanceofa
carcinogenicresponse,ratherthanstatisticsalone.Itwaspointedoutthatalltumoursarebiologically
significantbutitisimportanttoknowwhethertheyarecompoundrelatedandthisis,inpart,based
onstatisticalanalysis.
3.27 TheproposalsincludedusingtheThresholdofToxicologicalConcern(TTC)approachtosettingDMELs
forsomaticcellmutagenswithnocancerdata.However,theCOMconsidersitprematureatpresent
tosetlevelssuchasTTCsformutagenswithnocancerdata,asnoagreementhadbeenreached
abouthowtoranksuchmutagens.
3.28 HSEcommentedthatthecommittee’scommentswouldbereportedtotheEUworkinggroupdrawing
upthisguidance.
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Horizon scanning
3.29 TheCOCundertakes“horizonscanning”exercisesatregularintervalstoidentifynewandemerging
issueswhichhavethepotentialtoimpactonpublichealth.Afteranextensiveliteraturesearch,a
numberoftopicswereidentifiedbythesecretariatforconsiderationbythecommitteeatthe2007
exercise.Fromthese,andcommitteemembers’ownproposals,theCOCconsideredthatthefollowing
topicsshouldbetakenforward,togetherwiththoseoutstandingfrom2006:
(cid:1) thecarcinogenicityofmixtures
(cid:1) furtherconsiderationoftheHumanrelevanceframework/Modeofaction
(cid:1) afurtherreviewofproteomics
(cid:1) mutationalspectra(jointlywiththeCOM).
Ongoing topics
Chlorinateddrinkingwaterandcancer
3.30 During2007,theCOCreviewedanumberofnewepidemiologicalstudiesonchlorinateddrinking
waterandcancer.Astatementwillbepublishedin2008.
Non-Hodgkin’slymphoma(NHL)
3.31 IncidenceratesforNHLhaveincreasedinallagegroupsinGreatBritaininrecentyears,particularly
duringtheearly1980sand1990s.Anumberofepidemiologicalstudieshavebeencarriedoutonthe
associationbetweenchemicalsandNHLandthecommitteereviewedtheseduring2007toseeif
thereisanyevidencethatexposuretoenvironmentalchemicalscouldhaveaccountedforthe
increaseinincidenceofNHL.Astatementwillbepublishedin2008.
Toxicogenomics
3.32 TheCOC,COMandCOTareupdatingtheirreviewoftoxicogenomics.TheCOChasfocussedontwo
areasinparticular:whethertoxicogenomicsisusefulindistinguishingbetweengenotoxicandnon-
genotoxicchemicals,andwhetheritisusefulintestingthehypothesisforamodeofactionorofhelp
inproposingamodeofactionforachemical.Ajointstatementwillbepublishedin2008.
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Statements of the COC
Statement on Prostate Cancer and Pesticide Exposure
Introduction
1 In2004thecommitteepublishedastatementonprostatecancer,inwhichwediscussedtheknown
andpotentialriskfactorsassociatedwiththisdisease.Thestatementincludedanevaluationofthe
epidemiologicalandotherdataonoccupationalgroupsandchemicalexposuresforwhichan
associationwithprostatecancerhasbeenproposed.Twooccupationalgroupswereconsidered:
rubberworkers,forwhomweconcludedthattherewasnoconvincingevidenceofanincreasedrisk
ofprostatecancer,andfarmers/farmworkers/pesticideapplicators.Inthecaseofthislattergroup,we
concluded:
"…thattherewassomelimitedevidencetosuggestanassociationbetweenfarmers/farmworkers,
exposuretopesticidesandincreasedriskofprostatecancer.Thepossibilityofsuchanassociation
beingcausalcouldnotbediscountedandthepublishedliteratureshouldcontinuetobe
monitoredforfurtherstudies.Thecommitteecommentedontheneedforimprovedmeasuresof
exposuretopesticidesandinparticularherbicides.Itwasconsideredthatthepotential
associationbetweenherbicideusebyfarmersandfarmworkersshouldbekeptunderreview"
(COC,2004)
2 Recently,wewereaskedbythePesticidesSafetyDirectorateoftheDepartmentoftheEnvironment,
FoodandRuralAffairs(Defra)toconsiderareportcommissionedfromtheInstituteofOccupational
Medicine(IOM)entitled"DeskStudyonProstateCancerandPesticideExposure"(IOM,2006)andto
adviseonwhetherthereportalterstheconclusionofour2004statement.Atthesametime,we
consideredanewlypublishedreviewandmeta-analysisofcohortstudiesofprostatecancerriskin
pesticidemanufacturingworkers(VanMaele-Fabryetal,2006).Wereporthereonourconclusions.
3 TheIOMreportisanarrativereviewoftheepidemiologyofoccupationalexposuretopesticidesand
theriskofprostatecancer,andofthepotentialmechanismsthatmightunderlieanyassociation.The
reportconcludesthatepidemiologicalstudiesofmanufacturingworkersexposedtopesticideshave
notreportedanexcessriskofprostatecancer.Italsoconcludesthattherearealargenumberof
studiesofagriculturalworkersexposedtopesticidesbutthat,nevertheless,theresultshavebeen
inconsistent:manyhavebeennegativeorinconclusive,withafewshowingpositiveresults.Wenote
thatthereportproposesthatpesticidesmightcauseprostatecancerthroughapotentialendocrine-
disruptingmechanismbasedonandrogenimbalance.Thisproposalmaybederivedfromdatathat
suggestthatlowdoseexposuretocertainchemicalsmayleadtoanincreaseinprostateglandweight
inyoungmice(vomSaaletal,1997)butthesedataaredisputedbyothers(AshbyJetal,1999)who
wereunabletoreproducetheseobservations.Moreover,pesticidesarenotagenericgroupof
chemicalsbutcomprisecompoundsofdifferentstructuresandbiologicalactivities.Itisunlikely,
therefore,thatasinglemechanismofactionwouldapplytoallpesticides.
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