SOS of EDCs 2012 Summary for DMs

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A summary and key messages prepared from an assessment of the state of the science ofendocrine disruptors (SOS EDCs 2012) prepared by a group of experts for the WorldHealth Organization and the United Nations Environment Programme.

Editors: ke Bergman, Susan Jobling, Jerrold J.Heindel, Karen Kidd and R.Thomas Zoeller

WHO logo UNEP logo UN Logo

State-of-the-Science ofEndocrine Disrupting Chemicals

2012

Summary for Decision Makers


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United Nations Environment Programme, 2012

This document is not a formal publication of the United Nations EnvironmentProgramme and the World Health Organization and all rights are reserved by theorganizations. The views expressed therein are not necessarily the views of theorganizations.

Contribution toIOMC ??????????????????????????????????????????????????????????????Pending agreement with participating organizations


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Whyareweconcernedaboutendocrinedisruptors?

SummaryforDecisionMakerswithKeyMessages

1.Introduction

Thisdocumentpresentssummaryinformationandkeymessagesfordecisionmakersonendocrine

disruptors,fromthefullreportentitled,StateoftheScienceofEndocrineDisruptingChemicals(SOSof

EDCs2012)

and

is

part

of

the

United

Nations

Environment

Programme's

(UNEP)

and

World

Health

Organization's(WHO)ongoingcollaborationtoaddressconcernsaboutthepotentialadverseeffectsof

anthropogenicchemicals.

Weliveinaworldinwhichmanmadechemicalshavebecomeapartofeverydaylife.Itisclearthat

someofthesechemicalpollutantscanaffecttheendocrine(hormonal)systemandcertainofthese

endocrinedisruptorsmayalsointerferewiththedevelopmentprocessesofhumansandwildlifespecies.

Followinginternationalrecommendationsin1997bytheIntergovernmentalForumonChemicalSafety

(IFCS)andbyEnvironmentalLeadersoftheEightregardingtheissueofendocrinedisruptingchemicals

(EDCs),thejointInternationalProgrammeonChemicalSafety(IPCS)ofWHO,UNEPandILO

(InternationalLabourOrganisation)developedin2002areportentitledGlobalAssessmentofthe

State

of

the

Science

of

Endocrine

Disruptors

(Figure

1)

Thegeneralconclusionsfromtheirworkwerethatthereissufficientevidencetoconcludethatadverse

endocrinemediatedeffectshaveoccurredinsomewildlifespeciesandthatexperimentaldatasupport

thisconclusion.TheIPCS2002documentfurtherconcludedtheneedforbroad,collaborativeand

internationalresearchinitiativesandpresentedalistofresearchneeds.

Since2002,intensescientificworkhasimprovedourunderstandingoftheimpactsofEDCsonhuman

andwildlifehealth.ThescientificreviewpublishedbytheEndocrineSocietyin2009andtheStateofthe

artassessmentofendocrinedisruptersperformedwithinEU(2011)showsthescientificcomplexityof

thisissue,withover500scientificarticlescitedthatfocusedonvariousaspectsofEDCs.

Thesereviews

concluded

that

there

is

emerging

evidence

for

adverse

reproductive

outcomes

(infertility,

cancers,malformations)fromexposuretoEDCs,andthereisalsomountingevidenceforeffectsof

chemicalsonthyroid,neuroendocrinesystem,obesityandmetabolism,andinsulinandglucose

homeostasis.

TheEndocrineSocietycalledfortimelyactiontopreventharm.AlsotheEuropeanSocietyforPaediatric

Endocrinology(ESPE)andtheUSbasedPediatricEndocrineSociety(PES)haveputforwardaconsensus

statementcallingforactionregardingendocrinedisruptorsandtheireffects.


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Nowin2012,UNEPandWHOincollaborationwithinternationalexpertsaretakingastepforwardby

developingadocumentonendocrinedisruptorswithscientificinformationonhumanandwildlife

impactsandkeymessagesfordecisionmakersandothersconcernedaboutthefutureofhumanand

wildlifehealth.

ThereportonEDCs2012providesthestateofthescienceofendocrinedisruptors.Itstartsbyasking

whatendocrinedisruptionisallaboutandthenreviewsendocrinedisruptingeffectsinhumansandin

wildlife.Finally,thedocumentreviewssourcesofandexposurestoEDCs.

2.KeyMessages

Humanandwildlifehealthdependsontheabilitytoreproduceanddevelopnormally.Thisisnotpossiblewithoutahealthyendocrinesystem.

Threestrandsofevidencefuelconcernsoverendocrinedisrupters.o Thehighincidenceandtheincreasingtrendsofmanyendocrinerelateddisordersinhumans.o Observationsofeffectsinwildlifepopulations.o Theidentificationofchemicalswithendocrinedisruptingpropertieslinkedtodisease

outcomesinlaboratorystudies.

Theendocrinerelateddiseaseburdeninthehumanpopulationishigherthanever,puttingourfuturegenerationsatrisk.

Evidencehasstrengthenedthatthereisariseinendocrinerelateddiseasesinthehuman

population.Althoughtimetrendsaresometimesdifficulttoestablish,duetothelackofuniform

diagnostic

criteria,

unfavorable

trends

have

become

apparent

in

a

number

of

countries.

o Largeproportions(upto40%)ofyoungmeninsomecountrieshavelowsemenqualitywhichreducestheirabilitytofatherchildren.

o Theincidenceofgenitalmalformationsinbabyboys,suchasnondescendingtestesandpenilemalformationshasincreasedovertime,orleveledoffatunfavorablyhighrates.

o Adversepregnancyoutcomes,suchaspretermbirthandlowbirthweight,haveincreasedinmanycountries.

o Neurobehavioralandthyroiddisordersaffectahighproportionofchildreninsomecountries,andhaveincreasedoverpastdecades.

o Globalratesofendocrinerelatedcancers(breast,endometrial,ovarian,prostate,testisandthyroid)havebeenincreasingoverthepast40to50years.

o Thereisatrendtowardearlieronsetofbreastdevelopmentinyounggirlsinallcountrieswhere

this

has

been

studied.

This

is

arisk

factor

for

breast

cancer.

o Theprevalenceofobesityandtype2diabeteshasdramaticallyincreasedworldwideoverthelast40years.WHOestimatesthat1.5billionadultsworldwideareoverweightorobeseand

thatthenumberwithtype2diabetesincreasedfrom153millionto347millionbetween1980

and2008.


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Closeto800hundredchemicalsareknowntobecapableofinterferingwithhormonereceptors,hormonesynthesisorhormoneconversion.Onlyasmallfractionofthesechemicalshavebeen

investigatedin

tests

capable

of

identifying

overt

endocrine

effects

in

intact

organisms.

o Thevastmajorityofchemicalsincurrentcommercialusehavenotbeentestedatall.o Thislackofdataintroducesenormousuncertaintiesaboutthetrueextentofrisksfrom

chemicalsthatpotentiallycoulddisrupttheendocrinesystem.

HumanandwildlifepopulationsallovertheworldareexposedtoEDCs.o ThereisglobaltransportofmanyEDCsthroughnaturalprocesses(oceanandaircurrents)as

wellasthroughcommerce,leadingtoworldwideexposuretoEDCs.

o Unliketenyearsago,weknowthathumansandwildlifeareexposedtofarmoreEDCsthanjustpersistentorganicpollutants(POPs).

o LevelsofsomenewerPOPsinhumansandwildlifearestillincreasing,andthereisalsoexposure

to

less

persistent

and

bioaccumulative

but

ubiquitous

chemicals.

o NewsourcesofexposuretoEDCsforhumans,inadditiontofoodanddrinkingwaterintake,havebeenidentified.

o Childrencanhavehigherexposurestochemicalsthanadults. Numerouslaboratorystudiessupporttheideathatchemicalexposurescontributetoendocrine

disordersinhumanandwildlife.ThemostsensitivewindowofexposuretoEDCsisduring

criticalperiodsofdevelopment.

o Developmentalexposurescancausechangesthat,whilenotevidentasbirthdefects,canleadtopermanentchangesthatleadtoincreasedincidenceofdiseasesthroughoutlife.

o Theseinsightsfromendocrinedisrupterresearchinanimalschangetheparadigmofcurrenttoxicological

testing

and

screening

from

the

study

of

exposures

in

adulthood

or

just

during

developmenttostudiesthatencompassexposuresduringsensitivewindowsinfetallife,

perinatallife,childhoodandpubertyandassessmentofeffectsacrossthelifespan.

Thespeedwithwhichtheincreasesindiseaseshaveoccurredinrecentdecadesrulesoutgeneticfactorsasthesoleplausibleexplanation.Evidenceisstrengtheningthatenvironmental

factors,includingexposurestoEDCs,contributetotheendocrinediseaseburden.

o Itisnotpossibletoprovethatanassociationbetweenchemicalexposureanddiseaseinthehumanpopulationiscausedbyanendocrinemechanism.Thusthehumandatalinking

exposuretoEDCsmustbeviewedinconjunctionwiththeanimalmodelandwildlifedata.

Worldwide,therehasbeenafailuretoadequatelyaddresstheunderlyingenvironmentalcausesof

these

worrying

disease

trends.

o Healthcaresystemsdonothavemechanismsinplacetoaddressthecontributionofenvironmentalriskfactorstotheendocrinediseaseburden.Thebenefitsthatcanberealized

byadoptingpreventativemeasuresfordealingwiththesediseaseshaveremainedlargely

unrealized.


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Wildlifepopulationshavebeenaffectedbyendocrinedisruption,withnegativeimpactsongrowthandreproduction.Theseeffectsarewidespreadandhavebeendueprimarilyto

persistentorganic

pollutants

(POPs).

Bans

of

these

chemicals

have

reduced

exposure

and

led

to

recoveryofsomepopulations.

o ItisthereforeplausiblethatadditionalEDCs,whichhavebeenincreasingintheenvironmentandareofrecentconcern,arecontributingtocurrentpopulationdeclinesinwildlifespecies.

Wildlifepopulationsthatarealsochallengedbyotherenvironmentalstressorsareparticularly

vulnerabletoEDCexposures

Humanandwildlifepopulationsallovertheworldareexposedtomanyofthesechemicalssimultaneously.Thetruehealthrisksthatstemfromsuchmixedexposuresareunderestimated

duetoconsiderationsofchemicalsonaonebyonebasis.Theeffectsofcombinedexposures

arenotappropriatelyaddressed.

o Endocrinedisruptersaregloballytransportedintheenvironmentthroughnaturalprocesses(oceanandaircurrents),leadingtoworldwideexposuretoEDCs.o Exposuretosomeofthesesubstanceshasriseninrecentyears.WhilethelevelsofsomePOPs

havedecreased,exposuretocertainmorerecentlydevelopedPOPsisincreasing,andthereis

alsoexposuretolesspersistentandbioaccumulativebutubiquitouschemicals.

o NewsourcesofexposuretoEDCshavebeenidentified. Internationallyagreedandvalidatedtestmethodsfortheidentificationofendocrinedisrupters

captureonlyalimitedrangeoftheknownspectrumofendocrinedisruptingeffects.This

increasesthelikelihoodthatharmfuleffectsinhumansandwildlifeareoverlooked.

o Formanyendocrinedisruptingeffects,agreedandvalidatedtestmethodsdonotexist,although

scientific

tools

and

laboratory

methods

are

available.

o Foralargerangeofhumanhealtheffects,therearenoviablelaboratorymodels.Thisseriouslyhampersprogresswithunderstandingthefullscaleofrisks.

DiseaseriskduetoEDCsisunderestimated.o AfocusonlinkingoneEDCtoonediseaseseverelyunderestimatesthediseaseriskfromEDCs.

WeknowthathumansandwildlifearesimultaneouslyexposedtomanyEDCsthusthe

measurementofthelinkagebetweenmixturesofEDCstodiseaseismorephysiologically

relevant.InadditionitislikelythatasingleEDCmaycausediseasesyndromesormultiple

diseases,anareathathasnotbeenadequatelystudied.

Animportantfocusshouldbeinreducingexposuresbyavarietyofmechanisms.Governmentbans,

while

limited,

have

been

effective

at

decreasing

exposures

(e.g.

to

lead,

chlorpyrifos,

TBT,

PCBsandsomeotherPOPs)andthereby,thehumanandwildlifediseaseburden.

DespitesubstantialadvancesinourunderstandingofEDCs,uncertaintiesandknowledgegapsstillexistthataretooimportanttoignore.Thishampersprogresstobetterprotectthepublic

andwildlife.Anintegrated,coordinatedinternationaleffortisneededtodefinetheroleofEDCs

incurrentdeclinesinhumanandwildlifehealthandinwildlifepopulations.


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3.EndocrineSystemsandEndocrineDisruption

Forpurposesofthispaperwehaveadoptedthedefinitionofanendocrinedisruptorthatwasusedin

theIPCS2002documentonendocrinedisruptors(SeethetextboxondefinitionofEDCs).Simplifiedthis

meansthat;endocrinedisruptorsarechemicals,orchemicalmixtures,thatinterferewithnormal

hormonesignaling.

Tounderstandendocrinedisruption,wemustunderstandthebasicfeaturesoftheendocrinesystem.

Theendocrinesystemisacomplexsystemconsistingofmanyinteractingtissuesthattalktoeachother

andtherestofthebodybychemicalsignalscalledhormones.Thehumanendocrinesystemisvisualized

intheFigure2.Itisresponsibleforcontrollingalargenumberofprocessesinthebodyincludingearly

processessuchascelldifferentiationduringdevelopmentandorganformation,tothecontrolofmost

tissueandorganfunctionsthroughoutadulthood(Figure3).Ahormoneisamoleculeproducedbyan

endocrineglandthattravelsthroughthebloodtoproduceeffectsondistantcellsandtissuesvia

integratedcomplexinteractingsignalingpathways.Thereareover50differenthormones,andhormone

relatedmolecules

(cytokines

and

neurotransmitters)

that

integrate

and

control

normal

body

functions

acrossandbetweentissuesandorgansoverthelifespan.Hormonesarecriticaltonormalfunctioningof

everytissueandorganinbothvertebratesandinvertebrates,indeedthehormonesandtheirsignaling

pathwaysarequiteconservedacrossspecies.

Endocrinedisruptorsarethuschemicalsthatinterfereinsomewaywithhormoneaction,andinso

doingcanproduceeffectswhichleadtoimpactsonhumanandwildlifehealth.

ThediversesystemsaffectedbyEDCslikelyincludeallhormonalsystemsandrangefromthose

controllingthedevelopmentandfunctionofreproductiveorganstothetissuesandorgansregulating

metabolismandsatiety.Effectsonthesesystemscanleadtoobesity,infertilityorreducedfertility,

learningandmemorydifficulties,adultonsetdiabetesorcardiovasculardiseaseaswellasavarietyof

otherdiseases.

We

have

only

recently

understood

that

EDCs

can

affect

the

systems

that

control

fat

developmentandweightgain.Thisisagoodexampleofcomplexphysiologicalsystemsthatare

influencedbyEDCsthatwerenotknownjustafewyearsago.Generally,therearetwopathwaysby

whichachemicalcoulddisrupthormoneaction:adirectactiononahormonereceptorproteincomplex,

oradirectactiononaspecificproteinthatcontrolssomeaspectofhormonedeliverytotherightplace

attherighttime(Figure3).BecauseEDCsactonthenormalhormonalorendocrinesystemstheyexhibit

thesamecharacteristicsashormonesasshowninTable1.

DefinitionofEDCs

Anendocrinedisruptorisdefinedinagenericsenseas,anexogenoussubstanceor

mixturethataltersfunction(s)oftheendocrinesystemandconsequentlycauses

adversehealtheffectsinanintactorganism,oritsprogeny,or(sub)populations.

Apotentialendocrinedisruptorisanexogenoussubstanceormixturethatpossesses

propertiesthatmightbeexpectedtoleadtoendocrinedisruptioninanintact

organism,or

its

progeny,

or

(sub)

populations.


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Table1. ComparisonofHormoneandEndocrinedisruptorAction

Hormones EndocrineDisruptors

Actvia

receptors

Somehavemultiplereceptors

Tissuespecificreceptorclassesandsubtypes

Hormonesnormallybindsimilarlytoall

receptorsubtypes

Someact

on

hormone

receptors

Willcauseabnormalreceptorsfunction

Likelyisoformspecificinteractions

Activeatlowdoses

Bloodlevelsdonotalwaysreflectactivity

Maybeboundtoserumproteinsinblood

withsmall%free

Nobioaccumulation

Someactatlowdoses,othersvariable

Bloodlevelsdonotalwaysreflectactivity

Maybeboundtoserumproteins

Effectsonhormonebloodlevelsmaynot

reflectonhormoneaction

Possiblebioaccumulation

Nonlineardoseresponserelationships

Alwayssaturablewithvariabledynamic

range

Canexhibitnonmonotonicdoseresponse

Highdoseeffectsnotsameaslowdose

Nonlineardoseresponserelationships

Alwayssaturablewithvariabledynamicrange

Canexhibitnonmonotonicdoseresponse

Highdoseeffectsnotsameaslowdose

Tissueandlifestagespecificeffects Tissueandlifestagespecificeffects

Developmentaleffectspermanent

Programsbrainandendocrinesystemfor

adultfunction

Developmentaleffectspermanent

Interfereswithprogrammingprocesses

Differentendpointsvaryinsensitivity Differentendpointsvaryinsensitivity

ThusEDCSdontactlikegeneraltoxicantsbutactlikehormones.Sincehormonesactviabindingto

receptors(Figure4)atverylowconcentrations,sodoEDCshavetheabilitytobeactiveatlow

concentrations,manyintherangeofcurrenthumanexposures.AlsoEDCsactonavarietyof

physiologicalprocessesinatissuespecificmannerandsometimesactviadoseresponsecurveswhich

arenotlinear(nonmonotonic).Indeeditisnotpossibletoextrapolatelowdoseeffectsfromhighdose

effects.Timingofexposuresisalsocriticalasexposuresduringdevelopmentandislikelyirreversible

whileadultexposuresseemtogoawaywhentheEDCisremoved.Itisimportantthatthesespecific

characteristicsofEDCsbetakenintoaccountwhenthetoxicityofchemicalswithpotentialEDCactivity

isassessed.

4.EndocrineDisruptorsandHumanHealth

ThedatalinkingexposurestoEDCsandhumandiseasesismuchstrongernowthanin2002.Since

humanstudiescanonlyshowassociationsandnotcauseandeffect,itisimportanttousebothhuman

andanimaldatatodeveloptheevidenceforalinkbetweenexposurestoEDCsandhumandisease.Even

soitmayneverbepossibletohaveabsolutecertaintythataspecificexposurecausesaspecificdisease

ordysfunctionduetothecomplexityofbothexposuresanddiseaseaetiology(Figure5)acrossthe

lifespan.

Ofparticularnoteisthatoverthepast10yearstherehasbeenadramaticshiftinfocusfrom

investigatingassociationsbetweenadultexposurestoEDCsanddiseaseoutcomestolinking


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developmentalexposurestodiseaseoutcomeslaterinlife.Thislatterapproachisnowconsideredthe

mostappropriateapproachformostEDdiseases/dysfunctionsbasedondatapresentedabove(Section

8) cf.Figure6.

Takingtheanimalmodeldataandhumanevidencetogether,thereisastronglikelihoodthatexposure

toEDCsduringfoetallifeand/orduringpubertyplaysaroleintheincreasesseenin male andfemale

reproductive,endocrinerelatedcancers,behaviouralandlearningproblemsincludingADHD,infections,

asthma,andperhapsobesityanddiabetesinhumans

5Why

are

we

concerned?

Human

Disease

Trends

Weareconcernedbecause:

Asignificantincreaseinreproductiveproblemsoverafewdecadesindicatesastrongroleofunidentifiedenvironmentalfactorsindiseaseaetiology.

Incidencesofendocrinecancers,e.g.testiscancer(Figure7)andbreastcancer(Figure8),havealsoincreasedduringthesameperiods;

Anincreasingnumberofchemicals,towhichallhumansinindustrializedareasareexposedhavebeenshowntointerferewiththeinternalhormonesynthesisormetabolism;

Experimentalanimalstudiesorinvitrostudieshaveshownthatmanyubiquitouschemicalscaninterferewiththedevelopmentandfunctionofmammalianendocrinesystems;

Therehasbeenadramaticworldwidedecreaseinhumanfertilityratesduringonegenerationandcurrentlythereisahighneedforassistedreproduction;

Finally,wearenowbeginningtoseeingstudiesshowingassociationsbetweenexposurestoEDCsandseveralhealthproblemsinhumansofallages.

ThereislittledoubtthatsomeEDCscaninteractwiththethyroidsysteminanimalsandhumans.

Normalthyroidfunctionisveryimportantfornormalbraindevelopment,particularlyperinatally.EDCs

havealsorecentlybeenlinkedtoasthma,birthdefects,neurodevelopmentaldisorders,obesity(Figure

9),cardiovasculardisease,diabetes,andmetabolicsyndrome.Manyofthesediseasesanddisordersare

increasing,somewithglobalfigures.Theglobalhealthexpenditureondiabetesalonewasexpectedto

total

$376

billion

USD

in

2010,

and

rise

to

490

billion

USD

in

2030fully

12%

of

all

per

capita

health

care

expenditures.

Therearealsootheralarmingtrendsinhumanpediatrichealth.Theprevalenceofpediatricasthmahas

morethandoubledoverthepast20years,andisnowtheleadingcauseofhospitalizationsandschool

absenteeism.Birthdefectsaretheleadingcauseofinfantdeathandcertainbirthdefects,suchasthose

ofthemalereproductiveorgansappeartobeontherise.Neurobehavioraldisorders,includingdyslexia,

mentalretardation,attentiondeficithyperactivitydisorder,andautism,affect510%ofbabiesborn;

autismspectrumdisordersnowoccurataratethatapproaches1%.Theincidenceofpediatricleukemia

andbraincancerhasrisenaswellastheincidenceoftesticularcancer.

CurrentexposuretoawidevarietyofEDCscanimpair

thehealthofourchildrenandtheirchildren!


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Thesearestarkhealthstatistics.Allof thesecomplexnoncommunicablediseaseshavebothagenetic

andanenvironmentalcomponentand,sincetheincreasesinincidenceandprevalencecannotbedue

solelyto

genetics,

it

is

important

to

focus

on

understanding

the

contribution

of

the

environment

in

thesechronicdiseasetrendsinhumans.

Estimateshavebeenmadethatasmuchas28%ofhumandiseasesanddisordersaredueto

environmentalfactors.Thisprovidesachallengetoidentifyandaddressthem,butalsoatremendous

opportunitytoimprovehumanhealthbyimprovingelementsoftheenvironmentthatimpactpublic

health.Therecognitionofthesechallengesandopportunities,alongwiththefactthatmanyofthemost

prevalentdiseasesareassociatedwiththeendocrinesystem,hasledtoafocusonEDCs.

6.EndocrineDisruptorsandWildlifeHealth

Thereareabundantdatalinkingchemicalexposurestodeteriorationsinwildlifehealth,but

uunderstandingtheroleofEDCsintheglobaldeclineofpopulationsorbiodiversityischallenging

becauseofthepresenceofothernaturalorhumaninducedstressors,mixturesofchemicals(bothEDCs

andnonEDCs),difficultyinassessingexposures,andourlimitedunderstandingoftheecologyofthe

population.Declinesintheabundanceofonespecieswillinturnaffectthehealthandbalanceofits

ecosystembecauseoftheinterdependenciesoforganismswithintheenvironment. Thebestevidence

thatEDCsaffectwildlifepopulationscomesfromlongtermmonitoring;numbersofbirdsandmolluscs

areclearlyincreasinginregionswheretheirexposurestopesticides(i.e.DDTandtributyltin)are

reduced.

Endocrinesystemfunctionandwildlifehealthhasbeencompromisedinspeciesaroundtheworld.

StudiesofsealcoloniesinheavilypollutedareasoftheBalticandNorthSeasfoundhighratesoffemale

reproductivepathologiesandreproductivefailure,whichcorrelatedwithindividualPOPcontamination.

PerturbationsofthyroidandbonehomeostasisarerelatedtoPCBlevelsingreyseals(Figure10).In

DutchandBelgiancoloniesofcommontern,eggswithhigherPOPstooklongertohatchandthese

chicksweresmallerinsize. EspeciallyintheUK,butalsoinothercountries,fishhavebeenwidely

affectedbyestrogensandantiandrogensinmunicipalwastewaters,resultinginincreasedlevelsofthe

eggyolkproteinvitellogeninandintersexinmales. Theantifoulantsinshippaints tinandtriphenyltin

havedisruptedmolluscsexualdevelopmentworldwide(Figure11). Bythe1970s,manyspecies,such

asthecommerciallyimportantoyster,havecollapsedinheavilypollutedareas.Reductionsinexposure

haveledtoarecoveryofthesepopulations.

Thereare

important

parallels

between

the

increasing

incidence

of

human

disorders

and

those

observed

inwildlife.Forexample,testicularnondescentwasobservedin68%ofmalesinapopulationofblack

deerinAlaska;similartrendswerealsoobservedinMontana,U.S.Thereisrecentevidencethatanimals

livingnearhumansalsohaveincreasingbodyweight.Moreover,studiesofPCBexposedwildlifehave

providedimportantinformationonexposurelevels,earlyandsubclinicaleffectsandclinical

neurotoxicityofthesechemicals. Themechanismsunderlyingtheeffectsandtheoutcomesof

exposuresareoftensimilartothoseinhumans.Indeed,linksbetweenanimalandhumanhealthare

longstanding.Forexample,thestudyofanimalviruseshasledtonewinsightsintothemolecular

mechanismsofsomehumancancers.


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Inwildlife,relationshipsbetweenendocrinediseasesanddisordersandenvironmentalcontaminationby

endocrinedisruptingcontaminantsarestronglysuggestedbyscientificdatainsomecontaminated

regionsoftheworld.Thesestudiesreflectmainlyreproductivehealthwithlimitedstudiesonother

partsof

the

endocrine

system.

Studies

of

wildlife

exposures

and

disease

in

areas

where

there

are

high

incidencesofnonreproductiveendocrinediseasescouldhelptoidentifychemicalcontributorstothe

causationofthesediseases,supporttheconclusionofcommonriskfactorsinsharedenvironmentsand

showthevalueofwildlifeasimportantenvironmentalindicators.

7.Whyareweconcerned?PopulationEffectsinWildlife

Weareconcernedbecause:

Thereisaworldwidelossofspeciesorreducedpopulationnumbersofamphibians,mammals,birds,reptiles,freshwaterandmarinefishes,andinvertebrates(Figure12.)

Endocrinedisruptingchemicalshavebeenshowntonegativelyaffectbodysystemsthatarecriticalforhealthandsurvivalofwildlife. ThereforeEDCscouldplayastrongroleintheetiology

ofwildlifediseasesanddisorders,specieslossandpopulationdeclines.

ThecurrentbodyburdensofpersistentorganicpollutantssuchasPCBs,organochlorinepesticidesandmethylmercuryinsomefisheatingbirdsandmarinemammalpopulationsareatlevels

knowntocauseeffectsonbreedingandontheimmunesystem(Figure13).Someofthese

populationsare

threatened

or

endangered.

Legal,technicalandethicalconstraintstoworkingwithwildlife,notablythoselistedunderendangeredspecieslegislation,preventresearchtoinvestigatechemicalcausesofpopulations

declinesintheseanimals.

Anincreasingnumberofchemicals,towhichwildlifeareexposed,havebeenshowntointerferewiththehormonalandimmunesystemsofwildlifespecies.Mostofthesechemicalsarenot

monitoredinecosystems.Exposedwildlifepopulationsareoftennotmonitoredeither.

Experimentalanimalstudieshaveshownthatmanyubiquitouschemicalscaninterferewiththedevelopmentandfunctionoftheendocrinesystemsofwildlife,leadingtoeffectsonbehaviour,

fecunditygrowthandsurvivalanddiseaseresistance.Thisincreasestheprobabilitythatexposure

toEDCscouldleadtopopulationleveleffectsinwildlife.

SubtleeffectsofEDCsonindividualsmayresultindevastatingeffectsonwildlifepopulationsoverthelongterm.But,thisishardtoproveuntilthedeclinesinpopulationsareevident,atwhichpointitmaybetoolatetosavethesespecies.Thisiscorroboratedbyhistoricalevidenceshowing

sucheffectsofPCBsandorganochlorinepesticidesonpopulationsofmarinemammalsandbirds.

ThereisnodoubtthatexposurestoEDCscanaffectthereproductivehealthofwildlifespecies,but

therehavebeenfewstudiestranslatingtheseeffectstoimpactsatthepopulationlevel.

Notwithstandingthis,higherratesofreproductiveproblemsarefoundinanimalswithhigherexposure

toEDCsthaninthoseexposedtolowerconcentrations.Inaddition,aslevelsofEDCsdecline,some

wildlifepopulationshaveshownrecovery.EvidencealsosuggeststhatEDCshaveaffectedimmune

EffectsofEDCsonwildlifedeclinewhentheirexposureisreduced.


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10

function,therebyresultinginincreasedsusceptibilitytoinfectiousdiseasesinvertebrates,notably

marinemammals.Takentogether,theevidencesuggeststhatexposuretoendocrinedisrupting

contaminantsplaysasignificantroleinwildlifehealthtrends.

8.SensitivePeriodsforEndocrineDisruptorActionWindowofexposure

HormonesandthusEDCswhichacttoalterhormoneactions,actatalltimesduringlife foetal

development,infancy, earlychildhood,puberty,adulthoodandinaging.Infact,thetimingofhormone

orEDCactiondeterminesthestrengthimpactoftheireffect.Intheadult,hormonesandEDCsare

thoughttohavetransienteffectsontargetcellsandtissues.ThusthehormoneorEDCshasaneffect

whenit

is

present,

but

when

the

hormone

or

EDC

is

withdrawn

the

effect

diminishes

much

like

insulin

levelsrisingwhenbloodsugarishigh,andthendecliningwhenbloodsugardeclines.

IncontrasttotheacuteactionsofhormonesorEDCsduringadulthood,theireffectsduring

development(inuteroandinfancyandearlychildhoodinhumans)canbepermanentiftheexposure

occursduringthetimeaspecifictissueisdeveloping.Thisiscalleddevelopmentalprogramming.

Hormonescontrolnormaldevelopmentoftissuesfromthefertilizedspermandeggtothefully

developedfetus.Sincesometissuescontinuedevelopingafterbirth likethebrainandreproductive

system thesensitiveperiodforthesetissuesisextended,somefordecadesafterbirth.Theimportant

pointisthatwhileatissueisstilldevelopingitismoresensitivetotheactionofhormonesandthus

EDCs. InadditionanexposuretoahormoneorEDCduringdevelopmentcanhavelonglastingeffects,

effects

that

may

not

show

up

for

decades

later.

ThemechanismswherebyEDCexposureduringdevelopmentcanalterthedevelopmentofspecific

tissuesleadingtoincreasedsusceptibilitytodiseaseslaterinlifeisjustbeginningtobeunderstood.Itis

clearthathormonesplayanimportantroleincelldifferentiationthatleadstothedevelopmentof

tissuesandorgans. Oncetissuesandorgansarefullydevelopedandactivethenhormoneshavea

differentrole,tocontrolintegrationofsignalsbetweentissuesandorgansystemtomaintainproper

balanceandnormalfunction.Developmentwhenhormonesarecontrollingcellchangestoformtissues

andorgansisthusaverysensitivetimeframeforEDCsaction.IfanEDCispresentduringthe

developmentalprogrammingofatissueitwoulddisruptthenormalhormonelevels,leadingtochanges

intissuedevelopment;changeswhichwouldbestableacrossthelifetimeconferringsensitivityto

diseaselaterinlife.Theseeffectsarenotlikelytobeevidentatbirthbutshowuponlylaterinlife,from

afew

months

to

decades

later

(Figures

14,15).

Thus

exposure

to

EDCs

during

development

is

so

serious

anddamagingbecausethechangesthatoccurdueexposuretoEDCsduringdevelopmentare

permanentbutinsidiousandsubtle,onlybeingdetectedoncomplexanalysisatthecellularlevel(Figure

16).Superficialassessmentatbirthmaynotdetectanyproblems.Thesedevelopmentaleffectsagain

indicatethatbabiesandchildrenarenotjustlittleadults!

EDCEffectsAcrossGenerations

EDCshavealsobeenshowntoalsoproduceeffectsthatcancrossgenerations,transgenerational

effects.Thuswhatapregnantmotherorwildlifeorganismisexposedtoduringpregnancymaynotonly

affectthedevelopmentofheroffspringbutalsotheiroffspringoverseveralgenerations.Theincreasein

Wildlifeacrosstheglobehavereproductiveproblemsanddiseases.


13/30

11

diseaseratesweareseeingtodaycouldbeinpartduetoexposuresofourgrandparentstoEDCs,and

theseeffectscouldincreaseovereachgenerationduetobothtransgenerationaltransmissionofthe

alteredprogrammingandalsocontinuedexposureacrossgenerations.

9.OccurrenceandExposurestoEndocrineDisruptors

Since2002,alargenumberofotherchemicalsthanpersistentorganicpollutants(POPs)havebeen

identifiedas

EDCs

and

these

include

chemicals

that

have

very

different

properties,

sources

and

fates

in

theenvironmentthanthePOPs.EDCsarebothmanmadeandnatural.Somearefoundinalargevariety

ofmaterials,products,articlesandgoods.Theymayalsobebyproductsformedduringmanufacturingor

combustionofwastes.EDCsarealsosubjectedtobiologicalandenvironmentaltransformationsthat

mayformotherEDCs.EDCsarefoundamongmanyclassesofchemicalsincludingPOPs,currentuse

pesticides,phytoestrogens,metals,activeingredientsinpharmaceuticals,andadditivesorcontaminants

infood,personalcareproducts,cosmetics,plastics,textilesandconstructionmaterials.Oncereleased

intotheenvironmentthemorepersistentchemicalscanbecarriedbyairandwatercurrentstoremote

locationsandmanycanbeconcentratedthroughfoodwebstohighlevelsinhumansandothertop

predators.Otherchemicalshaveshorterlifespansintheenvironmentbutareregularlyreleasedin

effluents,inrunofffromagriculture,orfromurbanenvironments,resultinginhighenvironmentallevels

nearthesource(Figure17).

WildlifeandhumansareexposedtoEDCsinseveraldifferentways.Air,water,soil,sediment,andfood

aresourcesofEDCsforwildlife.HumanexposuretoEDCsoccursviaingestionoffood,dustandwater,

inhalationofgasesandparticlesintheair,anddermaluptake(Figure18).TransferofEDCsfromthe

mothertothedevelopingfetusthroughtheplacentaandtooffspringinmothersmilkalsooccursfor

bothwildlifeandhumans.ChildrencanhavehigherexposurestoEDCsbecauseoftheirhandtomouth

activities.ThesemultipleroutesofexposuretoavarietyofEDCsmeanthathumansandwildlifeare

exposedtocomplexmixturesofEDCs.Atthistimetherearenodatashowinghowmixturesofvirtually

hundredsof

EDCs

at

low

concentrations

will

affect

human

health

and

wildlife.

Animal

studies

indicate

thatmixturesofchemicalsproduceadditiveeffects.Thushundredsofchemicalseachatlevelsbelow

toxicitycouldinteracttogethertocausehealthproblems.

Severalhundredenvironmentalpollutantshavebeenmeasuredinhumansandwildlifearoundthe

world,eveninremoteplacesliketheArctic.LevelsofEDCsinhumanandwildlifevarywiththeir

location;somearehigherinpeopleandwildlifeinurbanorhighlyindustrializedareasorsiteswhere,for

example,disposalofewasteoccurs,whereasothersarehigherinremoteenvironmentsbecauseoflong

rangetransportbyairandoceancurrentsandfoodwebaccumulation.Afewexamplesofexposure

aroundtheworldareshownintheFigures19and20.Therearenolongeranypristineareaswithout

Theincreasedincidenceofdiseasestodaycouldbetheresultofexposures

ofourgrandmothersandmotherstoEDCs.Similarly,exposurestoday

couldaffectgenerationstocome!

HumanandwildlifeexposuretoEDCscomesfromhighlydiversesources.


14/30

12

environmentalpollutants.Inaddition,levelsofchemicalsinthebodyaretightlylinkedtotrendsintheir

use.Therearegoodexampleswherebansorreductionsinchemicalusehaveresultedinreducedlevels

inhumansandwildlife.Indeed,concentrationsofmanyPOPshavedeclinedbecausetheyarebeing

phasedout

of

use.

In

contrast,

EDCs

that

are

being

used

more

now

are

found

at

higher

levels

in

humans

andwildlife.Itisnotablehowwellproductionandexposurearefollowingeachother,asexemplifiedin

Figure21.

HundredsofchemicalsincommerceareknowntohaveEDeffects.However,thousandsofchemicalsare

notlookedforbyanychemicalmethods. Itislikelythatthesechemicalsarecontributingtowildlifeand

humanexposurestoEDCstheexposome.ThesituationisdescribedinFigure22.Sinceonlyavery

limitednumberofallchemicalsincommercehavebeentestedfortheirendocrinedisruptingproperties,

theremaybemanymorewithsuchproperties.AlsotheEDCmetabolitesorenvironmental

transformationproducts,thebyproductsandproductsformeduponwastetreatmentarenotincluded

andtheirEDeffectsaremainlyunknown.

10.Thetipoftheiceberg.

Becauseonlyasmallpercentageofthe145,000chemicalsincommercetodayhavebeenassessedfor

endocrinedisruptingactivityandbecausemanychemicalsinconsumerproductsarenotidentified,we

haveonlylookedatthetipoftheiceberg. HowmanyEDCsarethere? Wheredotheycomefrom?

Whatarethehumanandwildlifeexposures? Whataretheireffectsindividuallyandinmixturesduring

developmentandadulthoodandevenacrossgenerations? Whataretheirmechanism(s)ofaction?

HowcantestingforEDCsbeimproved?Allofthesequestionsneedanswers.

11.Testing

for

EDCs

ItiscustomaryforregulatoryagenciestotestchemicalsforEDactivityusingspecificvalidatedguideline

studiesthatexaminethreehighdosestodetermineaNOAEL(noadverseeffectlevel)andthen

extrapolatingdownusingsafetyfactorstodeterminesafelevelsforhumansand/orwildlife. Thedoses

declaredsafearenotactuallytested. ThesestudiesalsoassumeathresholdforEDCeffects,thatthere

willbenoeffectsatlowdosesandthatthedoseresponsecurvewillbelinear.Asnotedaboveitisnow

clearthatEDCswillhavenothresholdduetothepresenceofactivehormonepathways,andthatEDCs

arelikelytohaveeffectsatlowdosesandthattheirdoseresponseswillnotbelinear.Sincethereare

datafromhumanepidemiologystudiesshowingeffectsonhumandiseasesendpointslinkedtoEDC

exposures,likelyoccurringatlevelstowhichhumansarecurrentlyexposed.

Regulatoryguidelinestudiesalsofocusonhistopathologyandorganandbodyweightsastheendpoints.

AsnotedaboveEDCscancausemanydiseases,diseaseendpointsthatarenotcurrentlyassessedin

regulatorystudies.Alsoriskassessmentapproachesdontalwaysassesstoxicityduringdevelopment,

whichisthemostsensitivetimeforEDCaction,andthenalsodonotfollowtheanimalsfortheir

lifetime,whichisneededtoassessresultingdiseases.


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13

12.LessonsfromthePast

SohowdoweasasocietyprotectourhealthandthatoffuturegenerationsfromtheactionsofEDCs?

Whatcanwelearnfromthepastthatwillhelpus?

Onescenarioistobanachemicalshowntocausetoxicityanddisease. Overthelast40yearsonlya

handfulofchemicalse.g.lead,POPs,tributyltin,somephthalateplasticizers,andchlopyrifos have

beenbannedinmostcountriesandsometimesthesebansonlyconcernspecificuses.Nonetheless,

therehavebeenclearbenefitsforhumanandwildlifehealthfromthedeclininguseofthesechemicals.

Oneofthebestexamplesofpositiveactionisthebanningofresidentialuseoftheorganophosphate

pesticidechlorpyrifosintheUSin2000.Chlorpyrifoshasbeenshowntobeapotentneurotoxicant

causingdevelopmental

delays,

attention

problems

and

ADHD

in

children.

Today

the

manufacturer

has

phasedoutproductsforresidentialusesaroundtheworld:itisstillusedworldwideasaninsecticideon

fruitsandvegetablesincommercialagriculture.FollowingtheresidentialbanintheUSchildrensblood

levelsinNewYorkdeclinedsignificantlywithinoneyearandwerereducedtolessthanhalfwithintwo

years.

Tributyltinisparticularlyinterestingasitwasbannedfromuseonshiphullsduetothereproductive

effectsithadonmarineanimals.Inharborswheretributyltinusehasdeclined,environmentallevels

havedecreasedandsotoohavetheeffectsofthisEDConthewildlifelivingintheseareas.Howeveritis

stillusedasafungicideonnumerousplantsandisandsomeformsoforganotinsmakeupacomponent

inPVCplastic.

POPslikePCBsandDDTwerebannedinmanycountriesover20yearsagoduetotheirenvironmental

persistenceandtoxicity.Asaresult,theirlevelsinhumansandwildlifehavedeclinedinrecentdecades.

BirdpopulationsexposedtohighlevelsofDDTinthe1950sthrough70sinNorthAmericaandEurope

areshowingclearsignsofrecovery(Figure23).Howevertherearestudiesshowingthatcurrentlow

levelsofthesepersistentchemicalsarestillcausingharmbecausetheyortheirbreakdownproducts

remainintheenvironmentlongaftertheyarenolongerused.

Leadisanimportantexampleofinactioninthefaceoftoxicitydata.Leadwasaknownneurotoxicant

sincetheRomantimes;nonethelessitwasusedingasolineandpaintaroundtheworld.Theimpactof

leadonchildrenisprofoundbecauseitcausesirreversibledamagetodevelopingboneandbraintissues.

ThemostdamagingimpactresultedfromtheuseofleadingasolinewhichcausedanestimatedIQloss

offivepointstomillionsofchildrenworldwide.

PCBswerebannedinthe1970sbecauseoftheirpersistenceinthe

environmentandpotentialcarcinogenicity.PCBsalsointerferewith

thyroid

hormone

system

affecting

childhood

learning

and

memory,

effectsthatwouldnotbeidentifiedusingcurrentgovernment

mandatedtoxicitystudies.


16/30

14

Thebanontetraethylleadingasolineonlyoccurredafterdecadesofinaction,whensubstituteswere

available. IndeedthebanwasnotspecificallybecauseofthedatashowingIQlossinchildrenassociated

withlead

exposure

around

the

world

but

due

to

the

economic

analysis

showing

it

cost

the

governments

lossofincomeduetolowereducationalachievement.Furtherleadinterferedwiththenewcatalytic

convertersoncarsusedtoreduceairpollution.Nonetheless,followingthebanintheUSleadlevelsin

childrenfelldramaticallyshowingthatthebanhadahugeimpact(Figure24).

Whiletheseareexamplesofsuccess,thescientificdatawaspresentmanyyearsbeforethepolicies

werechangedandthechemicalwasbanned.Duringthattimechildrenshealthcontinuedtobeharmed.

Sothequestioniswhenaretheresufficientdatatoact?Perhapstheanswerisinmakingmoreuseof

theprecautionaryprincipletobanorrestrictchemicalsinordertoreduceexposureearly,evenwhen

therearesignificantbutincompletedataandbeforethereissignificantandlonglastingharm.

13.ConcludingRemarks

Endocrinedisruptingchemicalshavethecapacitytointerferewithtissueandorgandevelopmentand

functionandthereforetheymayaltersusceptibilitytodifferenttypesofdiseasesthroughoutlife.Thisis

aglobalthreatthatneedstoberesolvedusingbothprovensolutionsthatareavailablebutunderutilized

andthedevelopmentofnewinnovativeapproachesandsolutions.

Progress

Wearestartingtounderstandwhendiseasesanddisordersstartandsomeimportantfactors,like

exposuretoEDCsduringdevelopmentandthroughoutthelifespan,thatinteractwithourgenetic

backgroundtoincreasesusceptibilitytoavarietyofdiseases.Itisclearthatmostifnotalldiseaseshave

theiroriginduringdevelopment.ItisalsoclearthatexposuretoEDCsduringdevelopmentcan,as

demonstratedinanimalmodels,andinanincreasingnumberofhumanstudies,resultinincreased

susceptibilitytoandincidenceofavarietyofdiseases.Theseincludethemajorhumandiseasesthatare

increasingaroundtheworld.Thesediseasesanddysfunctionsareincreasedatlevelsofexposurewithin

thenormalhumanpopulation.Itisalsoclearfromhumanstudiesthatweareexposedtoperhaps

hundredsofenvironmentalchemicalsatanyonetime.Itisnowvirtuallyimpossibletoexaminean

unexposedpopulationaroundtheglobe.Thereisanincreasingburdenofdiseaseacrosstheglobe,and

perhapsforfuturegenerationstowhichEDCsarelikelyplayinganimportantrole!

Futureneeds

WiththeinformationthatispresentlyavailableaboutadverseeffectsofEDCswearenowpoisedtohave

animportant

impact

on

disease

prevention.

While

much

of

the

worlds

focus

is

on

intervention

with

drugstoreducetheimpactofdisease,acostlyandineffectiveprocess,wecanusetheinformationon

howandwhenEDCsacttoactuallypreventdiseasefromoccurringbyreducingexposuresduring

development. Thisisaprovensolutionasdescribedaboveforlead.Preventionofdiseaseisalways

betterthanintervention,bothintermsofcostandhumansufferingverseshealthandwellbeing:the

benefitsofearlyactionoutweighthecosts.

Totakeadvantageofourcurrentknowledgetoimprovehumanandwildlifehealthbypreventionof

environmentallyinduceddiseasewehaveidentifiedthefollowingneeds.


17/30

15

A.StrengtheningKnowledgeofEDCs:Itiscriticaltomovebeyondthepiecemeal,onechemicalatatime,onediseaseatatime,onedoseapproachcurrentlyusedbyscientistsstudyinganimalmodels,

humansorwildlife. Understandingtheeffectsofthemixturesofchemicalsthathumansandwildlifeare

exposedto

is

increasingly

important.

Assessment

of

EDC

action

by

scientists

needs

to

take

into

account

thecharacteristicsoftheendocrinesystemthatarebeingdisruptede.g.lowdoseeffectsandnon

monotonicdoseresponses,tissuespecificityandwindowsofexposuresacrossthelifespan.Team

sciencethatcombinesknowledgefromwildlife,animalandhumanstudiesisneededtoprovideamore

holisticapproachforidentifyingthechemicalsthatareresponsiblefortheincreasedincidenceof

diseaseanddysfunction.TheknownEDCsmaynotberepresentativeofthefullrangeofmolecular

structuresandpropertiesduetoafartoonarrowfocusonhalogenatedchemicalsformuchexposure

assessmentsandtestingforEDeffects.ThusresearchisneededtoidentifyotherpossibleEDCs.

Endocrinedisruptionisnolongerlimitedtoestrogenic,androgenicandthyroidpathways.Chemicals

alsointerferewithmetabolism,fatstorage,bonedevelopment,theHPAaxis,andtheimmunesystem

andthissuggeststhatallendocrinesystemscanandwillbeaffectedbyEDCs.Together,thesenew

insightsstress

acritical

need

to

acquire

abetter

understanding

of

the

endocrine

system

to

determine

howEDCsaffectnormalendocrinefunction,howwindowsofexposuremayaffectdiseaseincidence

(particularlyforchildhoodrespiratorydiseases),andhowtheseeffectsmaybepassedontogenerations

tocome.

Furthermorenewapproachesareneededtoexaminemixturesofendocrinedisruptorsondisease

susceptibilityandetiologyasexaminationofoneendocrinedisruptoratatimeislikelytounderestimate

theriskfromendocrinedisruptors.AssessmentofhumanhealthduetoEDCsneedstoinvolveboththe

assessmentofchemicalmixturesonasinglediseaseaswellasasingleexposureonmultiplediseases.

Sincehumanstudies,whileimportantcannotshowcauseandeffect,itiscriticaltodevelopmechanistic

andcauseandeffectdatainanimalstosupportthestudiesonhumans.

B.ImprovedTestingforEDCs:Itisimportanttorecognizethattheidentificationofhumanorwildlifehealtheffectsofchemicalexposuresinepidemiologicalstudiesisanindicationthatthepremarket

evaluationofchemicaleffectsfailedtoaccuratelypredicttheirtoxicity.

Relevantanimaltestswithwhichtoensurethesafetyofwildlifepopulationsfromendocrinedisruptors

arenotavailableformostwildlifegroups.Formanyinvertebratespecies,essentialforthehealthy

functioningofecosystems,basicknowledgeoftheirendocrinesystemsislacking,makingitimpossible

todevelopassaystoidentifyendocrinedisruptingchemicalsthatcouldharmtheseanimals.

TestingstrategiescurrentlyemployedaroundtheworldarebasedonthepremisethatEDCscanbe

evaluatedinthesamemannerasacutetoxicants;thisimpliesthattestsathighdoseswillinformus

aboutlowdoseexposures.Italsoimpliesthatoneendpointofhormoneactioncaneffectivelybeused

topredicttheactionofanEDCatallendocrineendpoints. However,aswehavenotedabove,hormone

actionisquitecomplexanddependsonthedevelopmentalstageandtheendpointbeingevaluatedand

thatEDCsactlikehormonesandnotasgeneraltoxicants. Therefore,itispredictablethatendocrine

disruptingchemicalswillexerteffectsthatarealsoquitecomplexandthatarenotcapturedusing

strategiesdesignedtodetectacutetoxicitywithalimitedrangeofexposureparadigms(onlythreehigh

dosestested)andendpointsevaluated).Manytestsdonotencompassthesensitivedevelopmental

periodoriftheydo,theyarenormallynotcarriedoutthroughoutlifetimetoassesslatenteffects.Thus


18/30

16

tomoveforwardthereisaneedforareassessmentofGovernmentmandatedtestingmethodsfocusing

onhowbesttodetectEDCs.

C.ReducingExposuresandtherebyVulnerabilitytoDisease:InordertopreventorreducehealtheffectsfromEDCs,itisimperativethatweknowtheEDCsthathumansandwildlifeareexposedto,and

whatthelevelsofEDCsareinblood,placenta,amnioticfluidandothertissues.Wealsoneedthis

informationacrosslifespans,sex,ethnicities(orspeciesofwildlife)andregions.Manyinformationgaps

currentlyexistwithregardtowhatisfoundinhumanandwildlifetissues,especiallyfordeveloping

countriesandforchemicalsthatarelesspersistentinthebody.Longtermrecordstounderstand

changesinexposuresexistonlyforPOPsandonlyforafewcountries.

Inaddition,thereisaneedtocontinueexpandingthelistofchemicalscurrentlyexaminedtoones

includedinmaterialsandgoods,andchemicalbyproducts;wecannotassessexposurewithoutknowing

thechemicalstotarget.Thecomprehensivemeasurementsofallexposureeventsduringlifetimeis

needed,as

opposed

to

single

time

biomonitoring,

and

this

requires

longitudinal

sampling,

particularly

duringcriticallifestagessuchasfoetaldevelopment,earlychildhoodandthereproductiveyears.

WildlifeandhumansareexposedtoawidevarietyofEDCsgreatlydifferingintheirphysicochemical

properties.Further,thesecompoundsaregenerallypresentattracelevelsandincomplexmatrices

requiringhighlyselectiveandsensitivemethods.Thewiderangeofdifferentcompoundclassesrequires

avarietyofanalyticalapproachesandtechniques,makingitchallengingtounderstandallofthe

differentchemicalsintheenvironmentandinhumanandwildlifetissues. Thereisagrowingneedto

developnewanalyticaltechniquesandapproachestoprioritizetheassessmentofEDC.Thereisglobal

transportofEDCsthroughnaturalprocesses(oceanandaircurrents)aswellascommerce,leadingto

worldwideexposures.NewroutesofexposuretoEDCs,inadditiontofoodintake,havebeenidentified

andincludeindoorenvironmentsandelectronicsrecyclinganddumpsitesindevelopingcountries.The

sourcesandroutesofexposuretoEDCsneedtobefurtherinvestigated.

D.Information:Identifyingendocrineactivechemicalsfromallofthechemicalsusedandreleasedworldwideisamajorchallengeanditislikelythatwearecurrentlyonlyassessingthetipofthe

iceberg. Itispossibletotracehighproductionvolumechemicals(HPVCs),butthatisnotthecasefor

thenumerousadditivesandprocesschemicals. Addinggreatlytothecomplexityaretheunknownor

unintendedbyproductsthatareformedduringchemicalsmanufacturing,duringcombustionprocesses,

andviaenvironmentaltransformations,thusaddingontothenumberofchemicalsinourenvironment.

Whiletheactiveingredientsinpharmaceuticalsandpesticideshavetobedocumentedonthefinal

product,thisisnotthecaseforchemicalsinarticles,materialsandgoods.Personalhygieneproducts

andcosmeticsrequiredeclarationsoftheingredientsandthenumberofchemicalsappliedinthis

sphereof

uses

counts

in

the

thousands.

Many

sources

of

EDCs

are

not

known

because

of

lack

of

chemicalconstituentdeclarationsinproducts,materialsandgoods. Weneedtoknowwherethe

exposuresarecomingfrom.

E.Creatingenablingenvironmentsforscientificadvances,innovationanddiseaseprevention:TheproblemofexposuretoEDCsandtheireffectsondiseaseinhumansandwildlifeisaglobalproblem

whichwillrequireglobalsolutions. Moreprogramsareneededwhichfostercollaborationsanddata

sharingamongscientistsandbetweengovernmentalagenciesandcountries.Toprotecthumanhealth

fromtheproblemsresultingfromthecombinedeffectsofEDCsexposuresandfrompoornutrition,and

poorlivingconditions,thereisaneedtodevelopprogramsandcollaborationsbetweendevelopedand


19/30

17

developingcountries.Thereisalsoneedtostimulatenewadaptiveapproacheswhichbreakdown

institutionalandtraditionalscientificbarriersandstimulateinterdisciplinaryandmultidisciplinaryteam

science.

[AlistoftheFiguresusedinthisdocumentwillfollow,referringtheiroriginandanypotentialscientificarticlefrom

wherethediagramswereredrawn.Copyrightpermitshavebeenobtainedforallillustrationshavingaparticular

source]


20/30

Introdu

Endocri

Figure2

hormon

tion(Sectio

eSystems

.Overview

esproduced

Figures

n1)

Fi

ndEndocri

fEndocrine

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forSum

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eDisruptio

System.Fig

maryfor

roftheIPC

n(Text

Sect

reshowse

Decision

2002docu

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docrinegla

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dsandso eexamplesof


21/30

Figure3

whenit

develop

affectp

Figure4

stimulat

actviar

.Sensitive

isforming.T

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.Exampleof

ethesynth

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roteins(6)

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22/30

Endocri

Figure5

Figure6

Whyar

Figure7

eDisrupto

.Diseases

in

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weconcer

.Testicular

sandHuma

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E

eamongth

ed? Huma

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mostvulne

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23/30

Figure8

Figure9

.Femalebr

.Incidence

astcanceri

foverweig

cidenceacr

tadultsins

ossEurope

veralcoun ries.


24/30

Endocri

Figure1

Figure1

genitali

eDisrupto

0.Greyseal

1.Common

.

sandWildli

scullwithhi

welk(Bucci

feHealth(T

ghlyeroded

umundatu

extSection

bonetissue

)showingi

6)

relatedtoP

mposex,i.e.

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ithasbothmaleandfe ale


25/30

Whyar

Figure1

Figure1

highlev

polybro

weconcer

2.Populatio

3.BritishCo

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ed? Popul

ndeclines

i

lumbiaskill

ulatedpoly

enylethers

ationEffect

wildlife

(ve

rwhales(O

hlorinated

(PBDEs).

sinWildlife

rtebrates)o

rcinusorca)iphenyls(P

(TextSectio

er30

years,

andharbou

CBs)andm

n7)

1970

200

seals(Pho

deratelevel

0.

avitulina)csofthe

ontain


26/30

Sensitiv

Figure1

Figure1

ePeriodsfo

4.Earlyexp

5.Examples

rEndocrine

suresinlife

ofdiseases

DisruptorA

maybema

dysfuction

tion Wind

ifestedany

riginatingf

owofexpo

timeinlife.

omearlyex

ure(TextS

osures.

ction8)


27/30

Figure1

todisea

Occurre

Figure1

here.

6.Whichchi

eonsetlat

nceandExp

7.EDCsfind

ldhasbeen

rinlife?

osurestoE

theirwayin

exposedto

docrineDis

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ruptors(Sec

nmentvia

developme

tion9)

ointanddi

tandisthu

fusesource

smoresusc

s,asexempl

ptible

ified


28/30

Figure1

inhalati

Figure1

marine

8.Exposure

nandskin

9.EDCs

are

ammals.

toEDCsco

ptake.

oundin

wil

esfromm

lifeworldw

ltiplesourc

ide;PFOS

co

es,entering

ncentration

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ingestion,

eight)in

li er

of


29/30

Figure2

concent

Figure2

timeco

student

0.SomeED

rations(ng/

1.Humane

rseofindus

.

sarehighe

fat)inbird

posuretoa

trialDEHPp

tinwildlife

tissues.

nEDCdecre

roductionin

fromareas

aseswhenp

Germanya

ithhighch

roductionis

dmediand

micaluse,

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.g.BDE209

describedb

fDEHPinu

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30/30

Figure2

environ

Lessons

Figure2

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occupie

Figure 2

2.Anillustr

entalmedi

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3.Wildlifep

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inOregon

4. Ban on le

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d in gasolin

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ffectedbyE

ospreyeggs

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DCscanrec

(ppmwet

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Date post:	03-Apr-2018
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SOS of EDCs 2012 Summary for DMs

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